Síndrome rara com anomalias congênitas múltiplas, incluindo aplasia/hipoplasia mamilar, deformidades nos pés e mãos, e alterações dentárias. Pode apresentar distúrbios metabólicos como hiperisoleucinemia e gastrosquise, associada a disfunção cardíaca.
Introdução
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Visão geral
A Síndrome dismórfico de origem metabólica é uma condição rara que afeta o desenvolvimento do corpo, causando alterações na forma (dismorfias) e problemas no funcionamento do metabolismo. Isso significa que o corpo pode ter dificuldade em processar certas substâncias, o que pode levar a uma variedade de sintomas. A condição é conhecida internacionalmente como 'Developmental anomaly of metabolic origin'.[1][2]
Sinais e sintomas
Os sinais e sintomas podem variar muito de pessoa para pessoa. As alterações mais comuns envolvem o formato dos ossos e dos dedos das mãos e dos pés. Por exemplo, podem ocorrer dedos dos pés desviados (desvio tibial do segundo e quinto dedos), dedos das mãos curvados (clinodactilia do segundo dedo), dedos curtos (hálux curto) e união anormal entre ossos das mãos e dos pés (sinostose de carpos/tarsos). Também é comum observar unhas com formato diferente (distrofia ungueal) e alterações na ponta dos dedos.[1][2]
Outros sinais incluem problemas nos dentes, como dentes incisivos superiores muito espaçados, falta de alguns dentes (oligodontia) e dentes mal posicionados. Podem ocorrer alterações nos mamilos, como ausência ou desenvolvimento incompleto (aplasia/hipoplasia dos mamilos) e ausência das mamas (aplasia mamária). Em alguns casos, há alterações nos ossos da clavícula (aplasia/hipoplasia das clavículas) e nos ossos das mãos (morfologia metacarpal anormal). Problemas nos olhos, como alterações no disco óptico e no cristalino, também podem fazer parte do quadro.[1][2]
Além das alterações físicas, a síndrome pode afetar o funcionamento de órgãos internos. Podem ocorrer problemas no coração (função ventricular cardíaca anormal), no fígado (encefalopatia hepática) e na coagulação do sangue (hipercoagulabilidade). Em alguns casos, há uma abertura na parede abdominal (gastrosquise) e níveis elevados de um aminoácido chamado isoleucina no sangue (hiperisoleucinemia).[1][2]
Causas genéticas
A Síndrome dismórfico de origem metabólica é causada por alterações (mutações) em diversos genes. Esses genes fornecem instruções para o corpo produzir proteínas essenciais para o funcionamento das mitocôndrias (as 'usinas de energia' das células) e para outras vias metabólicas importantes. Até o momento, foram identificados 12 genes associados a esta condição.[1][3]
Os genes conhecidos incluem: FH, NDUFV2, PIGL, GPHN, MECR, HSD17B4, AIFM1, MOCS1, MT-ND2, LIPT1, TYMP e UQCC2. Cada um desses genes tem uma função específica, e uma mutação em qualquer um deles pode interromper processos metabólicos normais, levando aos sinais e sintomas observados na síndrome.[1][3]
Diagnóstico
O diagnóstico é baseado na avaliação clínica dos sinais e sintomas, especialmente as alterações físicas (dismorfias) e os problemas metabólicos. Para confirmar o diagnóstico, o médico pode solicitar exames genéticos. Atualmente, existem 336 tipos de testes genéticos disponíveis para investigar esta condição. Além disso, há 1.380 variantes genéticas registradas no banco de dados ClinVar que podem estar associadas à síndrome.[1][3]
Tratamento e manejo
Não existe um tratamento único para a Síndrome dismórfico de origem metabólica. O manejo é individualizado e foca no alívio dos sintomas e no suporte às funções do corpo. O tratamento pode envolver uma equipe multidisciplinar, incluindo geneticistas, cardiologistas, hepatologistas, ortopedistas, dentistas e outros especialistas, dependendo das necessidades de cada pessoa.[1]
No Brasil, a condição possui cobertura mínima pelo Sistema Único de Saúde (SUS), o que significa que alguns procedimentos e consultas podem ser acessados, mas a cobertura pode variar. É importante conversar com o médico sobre as opções disponíveis e o melhor plano de cuidado para cada caso.[1]
Prognóstico e qualidade de vida
O prognóstico e a qualidade de vida dependem da gravidade dos sintomas e dos órgãos afetados em cada pessoa. Como a síndrome é rara e os sintomas variam muito, não é possível fazer uma previsão geral. O acompanhamento médico regular e o tratamento dos sintomas são fundamentais para melhorar a qualidade de vida e o bem-estar.[1]
Conteúdo informativo gerado e mantido automaticamente a partir de fontes oficiais (Orphanet, HPO, OMIM, SUS). Não substitui avaliação médica.
A **síndrome dismórfico de origem metabólica** é uma categoria que reúne malformações físicas causadas por alterações no metabolismo do corpo. As alterações costumam ser percebidas no nascimento ou infância por meio de diferenças no formato dos dedos, dentes espaçados, alterações nos mamilos ou problemas no coração e no fígado. O quadro está associado a variações em diversos genes, como FH e NDUFV2, que afetam funções enzimáticas vitais. Esta condição não consta na lista oficial de PCDTs de doenças raras do Ministério da Saúde, não havendo remédio específico dispensado pelo SUS para a síndrome em si. O cuidado é focado em acompanhar e tratar cada sinal clínico conforme a necessidade individual de cada pessoa.
Síndrome rara com anomalias congênitas múltiplas, incluindo aplasia/hipoplasia mamilar, deformidades nos pés e mãos, e alterações dentárias. Pode apresentar distúrbios metabólicos como hiperisoleucinemia e gastrosquise, associada a disfunção cardíaca.
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Sinais e sintomas
O que aparece no corpo e com que frequência cada sintoma acontece
Partes do corpo afetadas
+ 1402 sintomas em outras categorias
Características mais comuns
Os sintomas variam de pessoa para pessoa. Abaixo estão as 3150 características clínicas mais associadas, ordenadas por frequência.
Linha do tempo da pesquisa
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Genética e causas
O que está alterado no DNA e como passa nas famílias
Genes associados
91 genes identificados com associação a esta condição.
Fumarase deficiency
A severe autosomal recessive metabolic disorder characterized by early-onset hypotonia, profound psychomotor retardation, and brain abnormalities, such as agenesis of the corpus callosum, gyral defects, and ventriculomegaly. Many patients show neonatal distress, metabolic acidosis, and/or encephalopathy.
Mitochondrial complex I deficiency, nuclear type 7
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN7 transmission pattern is consistent with autosomal recessive inheritance.
Coloboma, congenital heart disease, ichthyosiform dermatosis, impaired intellectual development, and ear anomalies syndrome
An extremely rare autosomal recessive multisystem disorder clinically characterized by colobomas, congenital heart defects, migratory ichthyosiform dermatosis, intellectual disability, and ear anomalies including conductive hearing loss. Other clinical features include distinctive facial features, abnormal growth, genitourinary abnormalities, seizures, and feeding difficulties.
Molybdenum cofactor deficiency C
A form of molybdenum cofactor deficiency, an autosomal recessive metabolic disorder leading to the pleiotropic loss of molybdoenzyme activities. It is clinically characterized by onset in infancy of poor feeding, intractable seizures, severe psychomotor retardation, and death in early childhood in most patients.
Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities
An autosomal recessive neurologic disorder characterized by childhood-onset dystonia, basal ganglia degeneration and optic atrophy with decreased visual acuity. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYTOABG severity is variable, and some patients lose independent ambulation.
D-bifunctional protein deficiency
Disorder of peroxisomal fatty acid beta-oxidation.
Combined oxidative phosphorylation deficiency 6
A mitochondrial disease resulting in a neurodegenerative disorder characterized by psychomotor delay, hypotonia, areflexia, muscle weakness and wasting. Some patients manifest prenatal ventriculomegaly and severe postnatal encephalomyopathy.
Molybdenum cofactor deficiency A
An autosomal recessive metabolic disorder leading to the pleiotropic loss of molybdoenzyme activities. It is clinically characterized by onset in infancy of poor feeding, intractable seizures, severe psychomotor retardation, and death in early childhood in most patients.
Leber hereditary optic neuropathy
A maternally inherited form of Leber hereditary optic neuropathy, a mitochondrial disease resulting in bilateral painless loss of central vision due to selective degeneration of the retinal ganglion cells and their axons. The disorder shows incomplete penetrance and male predominance. Cardiac conduction defects and neurological defects have also been described in some LHON patients. LHON results from primary mitochondrial DNA mutations affecting the respiratory chain complexes.
Lipoyltransferase 1 deficiency
An autosomal recessive disorder due to a defect in lipoic acid metabolism, resulting in severe lactic acidosis and metabolic decompensation. Variable clinical manifestations include delayed psychomotor development, severe hypotonia, dystonia, loss of head control, coma, bradycardia, and pulmonary hypertension.
Mitochondrial DNA depletion syndrome 1, MNGIE type
A multisystem disease associated with mitochondrial dysfunction. It is clinically characterized by onset between the second and fifth decades of life, ptosis, progressive external ophthalmoplegia, gastrointestinal dysmotility (often pseudoobstruction), diffuse leukoencephalopathy, cachexia, peripheral neuropathy, and myopathy.
Mitochondrial complex III deficiency, nuclear type 7
A form of mitochondrial complex III deficiency, a disorder of the mitochondrial respiratory chain resulting in a highly variable phenotype depending on which tissues are affected. MC3DN7 is characterized by severe intrauterine growth retardation, neonatal lactic acidosis and renal tubular dysfunction. Additional clinical features include a dysmorphic facial appearance, delayed psychomotor development, autistic features, aggressive behavior, and mild sensorineural hearing loss.
Mitochondrial complex III deficiency, nuclear type 5
A disorder of the mitochondrial respiratory chain resulting in a highly variable phenotype depending on which tissues are affected. Clinical features include mitochondrial encephalopathy, psychomotor retardation, ataxia, severe failure to thrive, liver dysfunction, renal tubulopathy, muscle weakness and exercise intolerance.
Adenosine monophosphate deaminase deficiency erythrocyte type
A metabolic disorder due to lack of activity of the erythrocyte isoform of AMP deaminase. It is a clinically asymptomatic condition characterized by a 50% increase in steady-state levels of ATP in affected cells. Individuals with complete deficiency of erythrocyte AMP deaminase are healthy and have no hematologic disorders.
Congenital disorder of glycosylation 2G
A multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. Clinical features of CDG2G include failure to thrive, generalized hypotonia, growth retardation and mild psychomotor retardation. CDG2G is biochemically characterized by a defect in O-glycosylation as well as N-glycosylation.
Mucopolysaccharidosis 3D
A form of mucopolysaccharidosis type 3, an autosomal recessive lysosomal storage disease due to impaired degradation of heparan sulfate. MPS3 is characterized by severe central nervous system degeneration, but only mild somatic disease. Onset of clinical features usually occurs between 2 and 6 years; severe neurologic degeneration occurs in most patients between 6 and 10 years of age, and death occurs typically during the second or third decade of life.
Pyruvate dehydrogenase E1-beta deficiency
An enzymatic defect causing primary lactic acidosis in children. It is associated with a broad clinical spectrum ranging from fatal lactic acidosis in the newborn to chronic neurologic dysfunction with structural abnormalities in the central nervous system without systemic acidosis.
Mucopolysaccharidosis 3A
A severe form of mucopolysaccharidosis type 3, an autosomal recessive lysosomal storage disease due to impaired degradation of heparan sulfate. MPS3 is characterized by severe central nervous system degeneration, but only mild somatic disease. Onset of clinical features usually occurs between 2 and 6 years; severe neurologic degeneration occurs in most patients between 6 and 10 years of age, and death occurs typically during the second or third decade of life. MPS3A is characterized by earlier onset, rapid progression of symptoms and shorter survival.
Pontocerebellar hypoplasia 1D
An autosomal recessive neurologic disorder with onset at birth or in infancy, and characterized by progressive axonal motor neuronopathy, severe generalized hypotonia, respiratory insufficiency, and cerebellar atrophy. Death in childhood may occur.
Mitochondrial DNA depletion syndrome 3
A disorder due to mitochondrial dysfunction characterized by onset in infancy of progressive liver failure, hypoglycemia, increased lactate in body fluids, and neurologic abnormalities including hypotonia, encephalopathy, peripheral neuropathy. Affected tissues show both decreased activity of the mtDNA-encoded respiratory chain complexes and mtDNA depletion.
Pontocerebellar hypoplasia 1A
A form of pontocerebellar hypoplasia, a disorder characterized by structural defects of the pons and cerebellum, evident upon brain imaging. PCH1A is an autosomal recessive form characterized by an abnormally small cerebellum and brainstem, central and peripheral motor dysfunction from birth, gliosis and spinal cord anterior horn cells degeneration resembling infantile spinal muscular atrophy. Additional features include muscle hypotonia, congenital contractures and respiratory insufficiency that is evident at birth.
Pontocerebellar hypoplasia 1B
A severe autosomal recessive neurologic disorder characterized by a combination of cerebellar and spinal motor neuron degeneration beginning at birth. There is diffuse muscle weakness, progressive microcephaly, global developmental delay, and brainstem involvement.
Pontocerebellar hypoplasia 1C
A severe autosomal recessive neurodegenerative disease characterized by cerebellar and corpus callosum hypoplasia, abnormal myelination of the central nervous system, and spinal motor neuron disease. Affected individuals manifest failure to thrive, severe muscle weakness, spasticity and psychomotor retardation. Vision and hearing are impaired.
Congenital disorder of glycosylation 2D
A multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions.
Mucopolysaccharidosis-plus syndrome
A form of mucopolysaccharidosis, a group of lysosomal storage diseases characterized by defective degradation of glycosaminoglycans, resulting in their excessive accumulation and secretion. The diseases are progressive and often display a wide spectrum of clinical severity. MPSPS is an autosomal recessive form characterized by coarse facial features, dysostosis multiplex, hepatosplenomegaly, respiratory difficulties, intellectual disability, developmental delay, pyramidal signs, severe chronic anemia, renal involvement and cardiac defects. Laboratory analyses show proteinuria with glomerular foamy cells, excess secretion of urinary glycosaminoglycans, and extremely high levels of plasma heparan sulphate. Disease onset is in infancy. Most patients die in the first years of life due to cardiorespiratory failure.
Neuropathy, ataxia, and retinitis pigmentosa
A syndrome characterized by variable combination of developmental delay, psychomotor retardation, hearing loss, optic atrophy and retinitis pigmentosa, dementia, seizures, ataxia, proximal neurogenic muscle weakness, and sensory neuropathy.
Leber hereditary optic neuropathy
A maternally inherited form of Leber hereditary optic neuropathy, a mitochondrial disease resulting in bilateral painless loss of central vision due to selective degeneration of the retinal ganglion cells and their axons. The disorder shows incomplete penetrance and male predominance. Cardiac conduction defects and neurological defects have also been described in some LHON patients. LHON results from primary mitochondrial DNA mutations affecting the respiratory chain complexes.
Mucopolysaccharidosis 1H
A severe form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. Patients with MPS1H usually present, within the first year of life, a combination of hepatosplenomegaly, skeletal deformities, corneal clouding and severe intellectual disability. Obstructive airways disease, respiratory infection and cardiac complications usually result in death before 10 years of age.
Hypophosphatasia
A metabolic bone disease characterized by defective skeletal mineralization and biochemically by deficient activity of the tissue non-specific isoenzyme of alkaline phosphatase. Four forms are distinguished, depending on the age of onset: perinatal, infantile, childhood and adult type. The perinatal form is the most severe and is almost always fatal. The adult form is mild and characterized by recurrent fractures, osteomalacia, rickets, and loss of teeth. Some cases are asymptomatic, while some patients manifest dental features without skeletal manifestations (odontohypophosphatasia).
Combined oxidative phosphorylation deficiency 40
An autosomal recessive mitochondrial disorder characterized by prenatal or infantile onset, fetal hydrops, severe hypertrophic cardiomyopathy, poor growth, sensorineural hearing loss, hepatic dysfunction, lactic acidosis, and decreased activities of mitochondrial respiratory complexes I, III, IV, and V. The disorder is lethal, with death occurring in infancy.
Combined oxidative phosphorylation deficiency 9
A mitochondrial disease characterized by failure to thrive, poor feeding, hypertrophic cardiomyopathy, hepatomegaly, and psychomotor retardation. Death in infancy has been observed in some cases.
Combined oxidative phosphorylation deficiency 8
A mitochondrial disease characterized by a lethal infantile hypertrophic cardiomyopathy, generalized muscle dysfunction and some neurologic involvement. The liver is not affected.
Leber hereditary optic neuropathy
A maternally inherited form of Leber hereditary optic neuropathy, a mitochondrial disease resulting in bilateral painless loss of central vision due to selective degeneration of the retinal ganglion cells and their axons. The disorder shows incomplete penetrance and male predominance. Cardiac conduction defects and neurological defects have also been described in some LHON patients. LHON results from primary mitochondrial DNA mutations affecting the respiratory chain complexes.
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 4
A disorder characterized by progressive weakness of ocular muscles and levator muscle of the upper eyelid. In a minority of cases, it is associated with skeletal myopathy, which predominantly involves axial or proximal muscles and which causes abnormal fatigability and even permanent muscle weakness. Ragged-red fibers and atrophy are found on muscle biopsy. A large proportion of chronic ophthalmoplegias are associated with other symptoms, leading to a multisystemic pattern of this disease. Additional symptoms are variable, and may include cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism.
Mucopolysaccharidosis 2
An X-linked lysosomal storage disease characterized by intracellular accumulation of heparan sulfate and dermatan sulfate and their excretion in urine. Most children with MPS2 have a severe form with early somatic abnormalities including skeletal deformities, hepatosplenomegaly, and progressive cardiopulmonary deterioration. A prominent feature is neurological damage that presents as developmental delay and hyperactivity but progresses to intellectual disability and dementia. They die before 15 years of age, usually as a result of obstructive airway disease or cardiac failure. In contrast, those with a mild form of MPS2 may survive into adulthood, with attenuated somatic complications and often without intellectual disability.
Combined oxidative phosphorylation deficiency 15
An autosomal recessive, mitochondrial, neurologic disorder characterized by features of Leigh syndrome and combined oxidative phosphorylation deficiency. Clinical features include mild global developmental delay, white matter abnormalities, ataxia, incoordination, speech and reading difficulties, T2-weighted hyperintensities in the basal ganglia, corpus callosum, and brainstem.
Mitochondrial complex I deficiency, nuclear type 12
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease.
Deafness, aminoglycoside-induced
A form of sensorineural deafness characterized by moderate-to-profound hearing loss and mitochondrial inheritance. It is induced by exposure to aminoglycosides.
Breast cancer
A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case.
Fanconi anemia complementation group C
A disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair.
Fanconi anemia complementation group B
A disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair. Some severe FANCB cases manifest features of VACTERL syndrome with hydrocephalus.
Temtamy preaxial brachydactyly syndrome
A syndrome characterized by multiple congenital anomalies, intellectual disability, sensorineural deafness, talon cusps of upper central incisors, growth retardation, and bilateral symmetric digital anomalies mainly in the form of preaxial brachydactyly and hyperphalangism.
Perrault syndrome 4
An autosomal recessive, sex-influenced disorder characterized by sensorineural deafness in both males and females, and ovarian dysgenesis in females. Affected females have primary amenorrhea, streak gonads, and infertility, whereas affected males show normal pubertal development and are fertile.
Peroxisome biogenesis disorder 2A
A fatal peroxisome biogenesis disorder belonging to the Zellweger disease spectrum and characterized clinically by severe neurologic dysfunction with profound psychomotor retardation, severe hypotonia and neonatal seizures, craniofacial abnormalities, liver dysfunction, and biochemically by the absence of peroxisomes. Additional features include cardiovascular and skeletal defects, renal cysts, ocular abnormalities, and hearing impairment. Most severely affected individuals with the classic form of the disease (classic Zellweger syndrome) die within the first year of life.
Auditory neuropathy and optic atrophy
An autosomal recessive disease characterized by hearing loss, visual impairment and optic atrophy, with onset in the first or second decades of life. Optic atrophy is caused by degeneration of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm and optic tracts.
Mucopolysaccharidosis 6
A form of mucopolysaccharidosis, a group of lysosomal storage diseases characterized by defective degradation of glycosaminoglycans, resulting in their excessive accumulation and secretion. The diseases are progressive and often display a wide spectrum of clinical severity. MPS6 is an autosomal recessive form characterized by intracellular accumulation of dermatan sulfate. Clinical features can include abnormal growth, short stature, stiff joints, skeletal malformations, corneal clouding, hepatosplenomegaly, and cardiac abnormalities.
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 1
A disorder characterized by progressive weakness of ocular muscles and levator muscle of the upper eyelid. In a minority of cases, it is associated with skeletal myopathy, which predominantly involves axial or proximal muscles and which causes abnormal fatigability and even permanent muscle weakness. Ragged-red fibers and atrophy are found on muscle biopsy. A large proportion of chronic ophthalmoplegias are associated with other symptoms, leading to a multisystemic pattern of this disease. Additional symptoms are variable, and may include cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism.
Mitochondrial complex V deficiency, nuclear type 5
A mitochondrial disorder characterized by childhood onset of episodic metabolic decompensation featuring lactic acidosis and hyperammonemia accompanied by ketoacidosis or hypoglycemia. Chronic manifestations include developmental delay, easy fatiguability, and 3-methylglutaconic aciduria. The transmission pattern of MC5DN5 is consistent with autosomal recessive inheritance.
Mitochondrial complex IV deficiency, nuclear type 2
An autosomal recessive, severe mitochondrial disorder characterized by hypotonia, global developmental delay, hypertrophic cardiomyopathy, lactic acidosis, gliosis, and neuronal loss in basal ganglia, brainstem and spinal cord. Serum lactate is increased, and laboratory studies show decreased mitochondrial complex IV protein and activity levels in various tissues, including heart and skeletal muscle. Most patients die in infancy of cardiorespiratory failure.
Mitochondrial complex IV deficiency, nuclear type 13
An autosomal recessive, infantile disorder with a fatal course in the first weeks of life, characterized by hypertrophic cardiomyopathy, left ventricular non-compaction, lactic acidosis, metabolic hypotonia, and mitochondrial complex IV deficiency.
Mitochondrial complex III deficiency, nuclear type 4
A disorder of the mitochondrial respiratory chain resulting in a highly variable phenotype depending on which tissues are affected. Clinical features include mitochondrial encephalopathy, psychomotor retardation, ataxia, severe failure to thrive, liver dysfunction, renal tubulopathy, muscle weakness and exercise intolerance.
Mitochondrial complex III deficiency, nuclear type 10
A form of mitochondrial complex III deficiency, a disorder of the mitochondrial respiratory chain resulting in a highly variable phenotype depending on which tissues are affected. MC3DN10 is an autosomal recessive form characterized by fetal bradycardia, poor feeding, hypotonia, hypertrophic cardiomyopathy, alopecia totalis, low mitochondrial complex III activity and lactic acidosis.
Mitochondrial complex I deficiency, nuclear type 3
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN3 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 22
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN22 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 21
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN21 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 2
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN2 inheritance is autosomal recessive.
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 3
A disorder characterized by progressive weakness of ocular muscles and levator muscle of the upper eyelid. In a minority of cases, it is associated with skeletal myopathy, which predominantly involves axial or proximal muscles and which causes abnormal fatigability and even permanent muscle weakness. Ragged-red fibers and atrophy are found on muscle biopsy. A large proportion of chronic ophthalmoplegias are associated with other symptoms, leading to a multisystemic pattern of this disease. Additional symptoms are variable, and may include cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism.
Mitochondrial DNA depletion syndrome 5
A disorder due to mitochondrial dysfunction. It is characterized by infantile onset of hypotonia, neurologic deterioration, a hyperkinetic-dystonic movement disorder, external ophthalmoplegia, deafness, variable renal tubular dysfunction, and mild methylmalonic aciduria in some patients.
Sulfite oxidase deficiency, isolated
A life-threatening, autosomal recessive neurometabolic disorder characterized by severe neurological impairment. Classic ISOD manifests in the first few hours to days of life and is characterized by intractable seizures, feeding difficulties, rapidly progressive encephalopathy, microcephaly, and profound intellectual disability. Children usually die during the first few months of life. Mild ISOD manifests in infancy or early childhood and is characterized by ectopia lentis that is variably present, developmental delay and regression, movement disorder characterized by dystonia and choreoathetosis, ataxia, and rarely acute hemiplegia due to metabolic stroke.
Pontocerebellar hypoplasia 6
A disorder characterized by an abnormally small cerebellum and brainstem, infantile encephalopathy, generalized hypotonia, lethargy and poor feeding. Recurrent apnea, intractable seizures occur early in the course of this condition.
Perrault syndrome 6
A form of Perrault syndrome, a sex-influenced disorder characterized by sensorineural deafness in both males and females, and ovarian dysgenesis in females. Affected females have primary amenorrhea, streak gonads, and infertility, whereas affected males show normal pubertal development and are fertile. PRLTS6 inheritance is autosomal recessive.
Peroxisome biogenesis disorder complementation group 9
A peroxisomal disorder arising from a failure of protein import into the peroxisomal membrane or matrix. The peroxisome biogenesis disorders (PBD group) are genetically heterogeneous with at least 14 distinct genetic groups as concluded from complementation studies. Include disorders are: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). ZWS, NALD and IRD are distinct from RCDP and constitute a clinical continuum of overlapping phenotypes known as the Zellweger spectrum (PBD-ZSS).
Peroxisome biogenesis disorder complementation group 4
A peroxisomal disorder arising from a failure of protein import into the peroxisomal membrane or matrix. The peroxisome biogenesis disorders (PBD group) are genetically heterogeneous with at least 14 distinct genetic groups as concluded from complementation studies. Include disorders are: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). ZWS, NALD and IRD are distinct from RCDP and constitute a clinical continuum of overlapping phenotypes known as the Zellweger spectrum (PBD-ZSS).
Peroxisome biogenesis disorder complementation group 3
A peroxisomal disorder arising from a failure of protein import into the peroxisomal membrane or matrix. The peroxisome biogenesis disorders (PBD group) are genetically heterogeneous with at least 14 distinct genetic groups as concluded from complementation studies. Include disorders are: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). ZWS, NALD and IRD are distinct from RCDP and constitute a clinical continuum of overlapping phenotypes known as the Zellweger spectrum (PBD-ZSS).
Peroxisome biogenesis disorder complementation group 1
A peroxisomal disorder arising from a failure of protein import into the peroxisomal membrane or matrix. The peroxisome biogenesis disorders (PBD group) are genetically heterogeneous with at least 14 distinct genetic groups as concluded from complementation studies. Include disorders are: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). ZWS, NALD and IRD are distinct from RCDP and constitute a clinical continuum of overlapping phenotypes known as the Zellweger spectrum (PBD-ZSS).
Spinocerebellar ataxia 28
Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA28 is an autosomal dominant cerebellar ataxia (ADCA) with a slow progressive course and no evidence of sensory involvement or cognitive impairment.
Phosphoglycerate dehydrogenase deficiency
An autosomal recessive inborn error of L-serine biosynthesis, clinically characterized by congenital microcephaly, psychomotor retardation, and seizures.
Multiple sulfatase deficiency
A clinically and biochemically heterogeneous disorder caused by the simultaneous impairment of all sulfatases, due to defective post-translational modification and activation. It combines features of individual sulfatase deficiencies such as metachromatic leukodystrophy, mucopolysaccharidosis, chondrodysplasia punctata, hydrocephalus, ichthyosis, neurologic deterioration and developmental delay.
Multiple congenital anomalies-hypotonia-seizures syndrome 3
An autosomal recessive syndrome characterized by distinct facial features, intellectual disability, hypotonia and seizures, in combination with abnormal skeletal, endocrine, and ophthalmologic findings including impaired vision, as well as abnormal motility of the eyes.
Mucopolysaccharidosis 3C
A form of mucopolysaccharidosis type 3, an autosomal recessive lysosomal storage disease due to impaired degradation of heparan sulfate. MPS3 is characterized by severe central nervous system degeneration, but only mild somatic disease. Onset of clinical features usually occurs between 2 and 6 years; severe neurologic degeneration occurs in most patients between 6 and 10 years of age, and death occurs typically during the second or third decade of life.
Mucopolysaccharidosis 7
A form of mucopolysaccharidosis, a group of lysosomal storage diseases characterized by defective degradation of glycosaminoglycans, resulting in their excessive accumulation and secretion. The diseases are progressive and often display a wide spectrum of clinical severity. MPS7 is an autosomal recessive form with a highly variable phenotype, ranging from severe lethal hydrops fetalis to mild forms with survival into adulthood. Most patients with the intermediate phenotype show hepatomegaly, skeletal anomalies, coarse facies, and variable degrees of mental impairment.
Mitochondrial complex IV deficiency, nuclear type 7
An autosomal recessive mitochondrial disorder characterized by encephalomyopathy resulting in variable clinical manifestations. Features include muscle weakness, gait disturbances, neurodegeneration, cognitive decline, metabolic acidosis, feeding difficulties, poor overall growth, cortical visual impairment, and hypertrophic cardiomyopathy. Serum lactate levels are increased. Patient tissues show decreased levels and activity of mitochondrial respiratory complex IV.
Mitochondrial complex IV deficiency, nuclear type 3
An autosomal recessive mitochondrial disorder characterized by cytochrome c oxidase deficiency. Clinical features include muscle weakness, hypotonia, ataxia, ptosis, metabolic acidosis, poor feeding, delayed motor development, anemia, sensorineural hearing loss, and cardiomyopathy.
Mitochondrial complex IV deficiency, nuclear type 1
An autosomal recessive disorder of the mitochondrial respiratory chain characterized by early-onset, rapidly progressive encephalopathy, neurodegeneration, and loss of motor and cognitive skills. Affected individuals show hypotonia, failure to thrive, loss of the ability to sit or walk, poor communication, poor eye contact, oculomotor abnormalities, as well as deafness, ataxia, tremor, and brisk tendon reflexes. Brain imaging shows bilateral symmetric lesions in the basal ganglia. Lactate levels in serum and cerebrospinal fluid are increased. Patient tissues show decreased levels and activity of mitochondrial respiratory complex IV. Death in childhood may occur, often due to central respiratory failure.
Mitochondrial complex II deficiency, nuclear type 1
A disorder of the mitochondrial respiratory chain with heterogeneous clinical manifestations. Clinical features include psychomotor regression in infants, poor growth with lack of speech development, severe spastic quadriplegia, dystonia, progressive leukoencephalopathy, muscle weakness, exercise intolerance, cardiomyopathy. Some patients manifest Leigh syndrome or Kearns-Sayre syndrome. MC2DN1 inheritance is autosomal recessive.
Mitochondrial complex I deficiency, nuclear type 6
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN6 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 37
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN37 features include developmental delay, cerebral atrophy, epilepsy, growth retardation, congenital myopathy with disproportion of fibers, and severely decreased activity of complex I. MC1DN37 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 17
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN17 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial DNA depletion syndrome 17
An autosomal recessive mitochondrial disorder characterized by childhood onset of rapidly progressive encephalopathy, stroke-like episodes, lactic acidosis, hypocitrullinemia, multiple defects of oxidative phosphorylation, mitochondrial complex I and IV deficiency, and reduced mtDNA copy number.
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 2
A disorder characterized by progressive weakness of ocular muscles and levator muscle of the upper eyelid. In a minority of cases, it is associated with skeletal myopathy, which predominantly involves axial or proximal muscles and which causes abnormal fatigability and even permanent muscle weakness. Ragged-red fibers and atrophy are found on muscle biopsy. A large proportion of chronic ophthalmoplegias are associated with other symptoms, leading to a multisystemic pattern of this disease. Additional symptoms are variable, and may include cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism.
Mevalonic aciduria
Accumulation of mevalonic acid which causes a variety of symptoms such as psychomotor retardation, dysmorphic features, cataracts, hepatosplenomegaly, lymphadenopathy, anemia, hypotonia, myopathy, and ataxia.
Pelger-Huet anomaly
An autosomal dominant inherited abnormality of granulocytes, characterized by abnormal ovoid shape, reduced nuclear segmentation and an apparently looser chromatin structure.
Medicamentos e terapias
Mecanismo: Alpha-galactosidase A stabiliser
Mecanismo: Interleukin-1 beta inhibitor
Mecanismo: Histamine H1 receptor antagonist
Mecanismo: Alpha-galactosidase A stabiliser
Mecanismo: Transferrin receptor binding agent
Mecanismo: Pyruvate dehydrogenase kinase inhibitor
Mecanismo: Ceramide glucosyltransferase inhibitor
Mecanismo: Ceramide glucosyltransferase inhibitor
Mecanismo: Phosphodiesterase 4 inhibitor
Variantes genéticas (ClinVar)
1.380 variantes patogênicas registradas no ClinVar.
Vias biológicas (Reactome)
161 vias biológicas associadas aos genes desta condição.
Diagnóstico
Os sinais que médicos procuram e os exames que confirmam
Tratamento e manejo
Remédios, cuidados de apoio e o que precisa acompanhar
Onde tratar no SUS
Hospitais de referência no Brasil e o protocolo oficial do SUS (PCDT)
🇧🇷 Atendimento SUS — Síndrome dismórfico de origem metabólica
Centros de Referência SUS
21 centros habilitados pelo SUS para Síndrome dismórfico de origem metabólica
Centros para Síndrome dismórfico de origem metabólica
Detalhes dos centros
Hospital Universitário Prof. Edgard Santos (HUPES)
R. Dr. Augusto Viana, s/n - Canela, Salvador - BA, 40110-060 · CNES 0003808
Serviço de Referência
Hospital de Apoio de Brasília (HAB)
AENW 3 Lote A Setor Noroeste - Plano Piloto, Brasília - DF, 70684-831 · CNES 0010456
Serviço de Referência
Hospital Estadual Infantil e Maternidade Alzir Bernardino Alves (HIABA)
Av. Min. Salgado Filho, 918 - Soteco, Vila Velha - ES, 29106-010 · CNES 6631207
Serviço de Referência
Hospital das Clínicas da UFG
Rua 235 QD. 68 Lote Área, Nº 285, s/nº - Setor Leste Universitário, Goiânia - GO, 74605-050 · CNES 2338424
Serviço de Referência
Hospital das Clínicas da UFMG
Av. Prof. Alfredo Balena, 110 - Santa Efigênia, Belo Horizonte - MG, 30130-100 · CNES 2280167
Serviço de Referência
NUPAD / Faculdade de Medicina UFMG
Av. Prof. Alfredo Balena, 189 - 5 andar - Centro, Belo Horizonte - MG, 30130-100 · CNES 2183226
Serviço de Referência
Hospital Universitário João de Barros Barreto
R. dos Mundurucus, 4487 - Guamá, Belém - PA, 66073-000 · CNES 2337878
Serviço de Referência
Hospital de Clínicas da Universidade Federal de Pernambuco
Av. Prof. Moraes Rego, 1235 - Cidade Universitária, Recife - PE, 50670-901 · CNES 2561492
Atenção Especializada
Instituto de Medicina Integral Prof. Fernando Figueira (IMIP)
R. dos Coelhos, 300 - Boa Vista, Recife - PE, 50070-902 · CNES 0000647
Serviço de Referência
Hospital de Clínicas da UFPR
R. Gen. Carneiro, 181 - Alto da Glória, Curitiba - PR, 80060-900 · CNES 2364980
Serviço de Referência
Hospital Universitário Pedro Ernesto (HUPE-UERJ)
Blvd. 28 de Setembro, 77 - Vila Isabel, Rio de Janeiro - RJ, 20551-030 · CNES 2280221
Serviço de Referência
Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira (IFF/Fiocruz)
Av. Rui Barbosa, 716 - Flamengo, Rio de Janeiro - RJ, 22250-020 · CNES 2269988
Serviço de Referência
Hospital Universitário Onofre Lopes (HUOL)
Av. Nilo Peçanha, 620 - Petrópolis, Natal - RN, 59012-300 · CNES 2408570
Atenção Especializada
Hospital São Lucas da PUCRS
Av. Ipiranga, 6690 - Jardim Botânico, Porto Alegre - RS, 90610-000 · CNES 2232928
Serviço de Referência
Hospital de Clínicas de Porto Alegre (HCPA)
Rua Ramiro Barcelos, 2350 Bloco A - Av. Protásio Alves, 211 - Bloco B e C - Santa Cecília, Porto Alegre - RS, 90035-903 · CNES 2237601
Serviço de Referência
Hospital Universitário da UFSC (HU-UFSC)
R. Profa. Maria Flora Pausewang - Trindade, Florianópolis - SC, 88036-800 · CNES 2560356
Serviço de Referência
Hospital das Clínicas da FMUSP
R. Dr. Ovídio Pires de Campos, 225 - Cerqueira César, São Paulo - SP, 05403-010 · CNES 2077485
Serviço de Referência
Hospital de Clínicas da UNICAMP
R. Vital Brasil, 251 - Cidade Universitária, Campinas - SP, 13083-888 · CNES 2748223
Serviço de Referência
Hospital de Clínicas de Ribeirão Preto (HCRP-USP)
R. Ten. Catão Roxo, 3900 - Vila Monte Alegre, Ribeirão Preto - SP, 14015-010 · CNES 2082187
Serviço de Referência
Instituto da Criança e do Adolescente (ICr-HCFMUSP)
Av. Dr. Enéas Carvalho de Aguiar, 647 - Cerqueira César, São Paulo - SP, 05403-000 · CNES 2081695
Serviço de Referência
UNIFESP / Hospital São Paulo
R. Napoleão de Barros, 715 - Vila Clementino, São Paulo - SP, 04024-002 · CNES 2688689
Serviço de Referência
Dados de DATASUS/CNES, SBGM, ABNeuro e Ministério da Saúde. Sempre confirme a disponibilidade diretamente com o estabelecimento.
Pesquisa ativa
Ensaios clínicos abertos e novidades científicas recentes
Pesquisa e ensaios clínicos
Nenhum ensaio clínico registrado para esta condição.
Publicações mais relevantes
Multi-omics investigation of thyroid development and dysfunction in down syndrome.
Down syndrome (DS), caused by trisomy of chromosome 21, is associated with a high prevalence of congenital non-autoimmune thyroid dysfunction, typically characterized by an elevated serum thyroid stimulating hormone (TSH) concentration. Early-life observational studies and fetal cordocentesis data, consistently reporting elevated TSH levels, suggest a developmental origin. However, the underlying pathophysiological mechanism remains unclear. This study aimed to investigate the molecular and developmental features underlying thyroid dysfunction in DS. Thyroid tissue of fetuses with DS (n = 4) and fetuses without a genetic/developmental abnormality (n = 5) were analyzed using histology, bulk RNA sequencing (RNA-seq), and DNA methylation (DNAm) profiling. Histological analysis revealed underdevelopment of DS fetal thyroid tissue, with smaller follicles and greater heterogeneity. RNA-seq identified 1035 differentially expressed genes (DEGs) distributed across the genome. Notably, three thyroid-relevant genes, FOXE1, IYD, and DIO2, were significantly downregulated in DS tissue. Gene set enrichment analysis (GSEA) showed widespread disruption of cellular processes. DNAm analysis identified 266 differentially methylated regions (DMRs), several of which overlapped with loci previously implicated in DS. Integration of expression and DNAm data revealed 20 significant integrative methylation-expression analysis associations, indicating cis-regulatory DNAm effects on gene expression. These findings suggest that congenital thyroid dysfunction in DS represents a DS-specific form of thyroid dysfunction, characterized by impaired thyroid development and altered expression and regulation of genes involved in thyroid function and general cellular processes. The genome-wide molecular changes observed likely result from gene dosage effects and systemic (epi)genomic disturbances caused by trisomy 21.
A Meier-Gorlin syndrome mutation impairs the loading of the MCM2-7 complex during DNA replication initiation.
Chromatin loading of the hexameric replicative helicase MCM2-7 complex requires coordinated interactions with the origin recognition complex (ORC), CDC6, and CDT1. MCM2-7 not bound to DNA forms a single hexamer (SH) with an open DNA entry gate between MCM2 and MCM5. Two MCM2-7 SHs can be loaded sequentially to form the double hexamer (DH) that encircles the DNA duplex. Activated MCM2-7 then unwinds DNA and initiates DNA replication. Our cryoelectron microscopy analyses show that a fraction of human MCM2-7 without DNA exists as DH. Unexpectedly, we find that the MCM3 winged helix domain (WHD) docks on MCM2 in both DNA-free DH and SH, creating a safety latch across the DNA entry gate to block DNA entry into the central channel. The safety latch can be opened by ORC-CDC6 binding. Perturbing this latch by structure-based or disease-related mutations of MCM3 causes replication defects and DNA damage checkpoint activation. Shortening the MCM3 linker between the helicase domain and WHD alleviates the cell cycle defects of the latch-strengthening mutation. Our findings uncover a regulated step in MCM2-7 loading with implications for human diseases.
Vesicular Glutamate Release Is Necessary for Neural Tube Formation.
The brain and spinal cord originate from a neural tube that is preceded by a flat structure known as the neural plate during early embryogenesis. In humans, failure of the neural plate to convert into a tube by the fourth week of pregnancy leads to neural tube defects (NTDs), birth defects with serious neurological consequences. The signaling mechanisms governing the process of neural tube morphogenesis are unclear. Here we show that in Xenopus laevis embryos, glutamate is released during neural plate folding in a Ca2+ and vesicular glutamate transporter-1 (VGluT1)-dependent manner. Vesicular release of glutamate elicits Ca2+ transients in neural plate cells that correlate with activation of Erk1/2. Knocking down or out VGluT1, globally or neural tissue-specifically, leads to NTDs and increased expression of Sox2, neural stem cell transcription factor, and neural plate cell proliferation. Exposure during early pregnancy to neuroactive drugs that disrupt these signaling mechanisms might increase the risk of NTDs in offspring.
Exploring extracellular vesicle MicroRNAs in Usher syndrome type 1B: Tear-Derived EVs as potential indicators of retinal health.
Usher syndrome type 1B (USH1B) is a rare inherited disorder characterized by congenital deafness and progressive retinitis pigmentosa, caused by biallelic pathogenic variants in the MYO7A gene. We explored extracellular vesicles (EVs) from two sources: human tears and iPSC-derived RPE cells from USH1B patients and controls. Tear EVs were assessed as a non-invasive biomarker source, while RPE-derived EVs provided insights into disease mechanisms in a controlled, cell-type-specific context. Although RPE differentiation was successful and MYO7A expression levels were similar between patients and controls, Myosin VIIA was not detected by western blot in the patient-derived cells. We examined the EV cargo by small non-coding RNAs (sncRNAs) sequencing from iPSC-RPE apical site and tears to identify molecular signatures of retinal degeneration. Tear EVs showed higher load and diversity of miRNAs than RPE-derived EVs, reflecting a broader ocular origin. Comparative analysis revealed shared retinal sncRNAs (hsa-miR-204, hsa-miR-211, hsa-miR-181a-5p) and group-specific differences. Notably, when comparing to controls, hsa-miR-200a-3p and hsa-miR-194-5p were upregulated in patient tear EVs, while let-7i/c-5p and hsa-miR-320a/b, were downregulated in-patient RPE-derived EVs. Pathway analysis linked these sncRNAs to retinal structure and function, including cytoskeletal remodeling and junctional integrity. Our findings highlight the potential of tear EVs as a non-invasive source of biomarkers that capture retinal molecular alterations in USH1B, with applications for diagnosis, monitoring, and therapeutic development. Although this is a pilot study focused on uncovering promising biomarkers rather than establishing definitive cause-effect mechanisms, it provides a foundation for future research with larger cohorts to validate and expand these findings.
A disrupted compartment boundary underlies abnormal cardiac patterning and congenital heart defects.
Failure of septation of the interventricular septum (IVS) is the most common congenital heart defect, but mechanisms for patterning the IVS are largely unknown. Here we show that a Tbx5+/Mef2cAHF+ progenitor lineage forms a compartment boundary bisecting the IVS. This coordinated population originates at a first and second heart field interface. Ablation of Tbx5+/Mef2cAHF+ progenitors causes IVS disorganization, right ventricular hypoplasia and mixing of IVS lineages. Reduced dosage of the congenital heart defect transcription factor TBX5 disrupts boundary position and integrity, resulting in ventricular septation defects and patterning defects, including misexpression of Slit2 and Ntn1, which encode guidance cues. Reducing NTN1 dosage partly rescues cardiac defects in Tbx5 mutant embryos. Loss of Slit2 or Ntn1 causes ventricular septation defects and perturbed septal lineage distributions. Thus, we identify Tbx5 as a candidate selector gene, directing progenitors and regulating essential cues, to pattern a compartment boundary for proper cardiac septation, revealing mechanisms for cardiac birth defects.
📚 EuropePMCmostrando 200
Etiological Analysis and Classification of 108 Patients with Infantile Epileptic Spasms Syndrome Based on the 2017 International League Against Epilepsy Classification.
Noro psikiyatri arsiviImaging of Congenital Anomalies and Developmental Abnormalities Involving the Arteries of the Head and Neck.
AJNR. American journal of neuroradiologyMulti-omics investigation of thyroid development and dysfunction in down syndrome.
Human molecular geneticsA Meier-Gorlin syndrome mutation impairs the loading of the MCM2-7 complex during DNA replication initiation.
Proceedings of the National Academy of Sciences of the United States of AmericaVesicular Glutamate Release Is Necessary for Neural Tube Formation.
The Journal of neuroscience : the official journal of the Society for NeuroscienceCirculating lncRNAs Remark Expression Profile of Cerebrovascular Malformation Endothelial Cells.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology[Van Wyk-Grombach syndrome as a result of late diagnosis of autoimmune thyroiditis (ait) in a patient with chromosome 22 deletion syndrome. Description of the clinical case and a brief review of the literature].
Problemy endokrinologiiNovel PKP2 compound heterozygous mutations causing neonatal early-onset arrhythmogenic cardiomyopathy: insights into the synergistic pathogenicity of biallelic inactivation.
Functional & integrative genomicsExploring extracellular vesicle MicroRNAs in Usher syndrome type 1B: Tear-Derived EVs as potential indicators of retinal health.
Cellular and molecular life sciences : CMLSRecent advances in understanding the pathogenesis, diagnosis, and treatment of tuberous sclerosis complex (TSC)-associated Lymphangioleiomyomatosis.
Biochemical pharmacologyDistinct genomic, microenvironmental, and nephron signatures in VHL kidney cysts and tumors.
Scientific reportsA disrupted compartment boundary underlies abnormal cardiac patterning and congenital heart defects.
Nature cardiovascular researchColloid cysts of the third ventricle show consistent expression of PAX8 but lack other features of thyroid, müllerian or intestinal differentiation.
Human pathologyMolecular impacts of Meier-Gorlin syndrome mutations on human origin licensing.
The Journal of biological chemistryIdentification of a De Novo MAGEL2 Pathogenic Variant in Schaaf-Yang Syndrome and the Importance of Paternal Allele Confirmation.
Journal of clinical laboratory analysisUltra-deep targeted next-generation sequencing with peripheral blood in patients with vascular malformations: a cohort of 40 patients.
Molecular biology reportsResting Energy Expenditure in Adults With Williams Syndrome: Comparative Accuracy of Predictive Equations.
Journal of intellectual disability research : JIDRBiological patterns of mouse embryonic palatal mesenchymal cells at different palatogenic stages.
Acta histochemicaAssessment of hormone measurement methods in girls with premature adrenarche, polycystic ovary syndrome, and non-classical congenital adrenal hyperplasia.
The Turkish journal of pediatricsNovel Compound Heterozygous Variants in the TCTN2 Gene Causing Meckel-Gruber Syndrome 8 in a Non-Consanguineous Chinese Family.
Molecular genetics & genomic medicinePreventing Differentiation Towards Primitive Macrophages in Stem Cells With Down Syndrome.
ImmunologyEpigenetic Drugs Splitomicin, Suberohydroxamic Acid, CPTH6, BVT-948, and PBIT Moderate Fibro-Fatty Development in Arrhythmogenic Cardiomyopathy.
BiomoleculesDentomaxillofacial abnormalities associated with rare bone disease in two pediatric populations from southern Europe and East Africa.
Orphanet journal of rare diseasesVenous Malformations: Unraveling Latest Mechanisms and Bridging Gaps in Targeted Therapy Development.
International journal of biological sciencesTracing the enteric neural crest cell pathway from origin to colonization: insights into Hirschsprung's disease.
Molecular biology reportsMultifaceted role of Iroquois signaling in development and diseases.
Molecules and cellsPOLYCYSTIC OVARY SYNDROME: ORIGINS AND IMPLICATIONS: PCOS in adolescents: ontogeny of neuroendocrine and metabolic disturbances.
Reproduction (Cambridge, England)The Endocrinological Basis for Polycystic Ovary Syndrome: An Evolutionary Perspective.
EndocrinologyImprinting Disorders and Epigenetic Alterations in Children Conceived by Assisted Reproductive Technologies: Mechanisms, Clinical Outcomes, and Prenatal Diagnosis.
GenesAtypical presentation of Acrodermatitis enteropathica in a child: later onset with life-threatening severe extensive dermatitis and septic shock.
BMC pediatrics[Aicardi-Goutières syndrome with atypical presentation: RNASEH2B gene mutation in an infant without microcephaly or intracranial calcifications (a case report)].
The Pan African medical journalGenetic requirement for Esrp1 and Esrp2 in vertebrate pituitary morphogenesis.
Development (Cambridge, England)Development and evaluation of image preprocessing pipelines for the Centiloid method on Down Syndrome data.
Alzheimer's & dementia : the journal of the Alzheimer's AssociationThe spectrum of neuromuscular diseases with tubular aggregates.
Neuromuscular disorders : NMDEvolution of angiogenic and inflammatory biomarkers in patients with hereditary hemorrhagic telangiectasia during treatment with bevacizumab: study protocol.
Revista clinica espanolaHighly variable genomic methylation in the Beckwith-Wiedemann syndrome associated with multi-locus imprinting disturbances.
Clinical epigeneticsPlasma proteome correlations with liver stiffness in pediatric cholestasis implicate epithelial to mesenchymal transition.
Hepatology communicationsIntramuscular enteric glia persist in Hirschsprung disease and undergo neurogenesis in response to GDNF-NCAM1 signaling.
Scientific reportsEffectiveness of therapy with recombinant human growth hormone (rhGH) in patients with hypoplastic left heart syndrome (HLHS) and short stature.
Endokrynologia PolskaUnexpected molecular mechanism of Orc6-based Meier-Gorlin syndrome: insights from a humanized Drosophila model.
GeneticsNovel variants in ZNF462 and phenotype update in patients with Weiss-Kruszka syndrome: a case series.
Translational pediatricsMCM5 UFMylation regulates replication origin firing and fork progression.
The EMBO journalAtypical mesenchyme in congenital pulmonary airways malformation: a promising new focus.
Respiratory researchFetal growth and congenital heart disease at high altitude.
Philosophical transactions of the Royal Society of London. Series B, Biological sciencesPTBP3 Associated With 9q32 Locus Is a Candidate Gene for Nager Syndrome.
Birth defects researchHigh-throughput assessment of FMR1 and SNRPN methylation-based newborn screening using IsoPure and QIAcube HT systems.
EpigenomicsContribution of rare coding variants to microcephaly in individuals with neurodevelopmental disorders.
Genome medicineMaternal PM2.5 Exposure and Cardiac Developmental Abnormalities in Fetuses and Neonates: Progressive Activation of the Complement and Coagulation Cascade.
Environmental science & technologyExcessive glycosylation drives thoracic aortic aneurysm formation through integrated stress response.
European heart journalIdentification of genetic and non-genetic modifiers of genomic imprinting through screening of imprinted DMR methylation in humans.
Epigenetics & chromatinPOLYCYSTIC OVARY SYNDROME: ORIGINS AND IMPLICATIONS: Epidemiological aspects of polycystic ovary syndrome.
Reproduction (Cambridge, England)Gene-environment interactions modulate the phenotype severity in mouse models of congenital craniofacial syndromes.
The Journal of clinical investigationConcentration-Response Analysis of the Combination of Pyronaridine and Piperaquine on Corrected QT Interval From a Randomized, Double-Blind, Placebo-Controlled Study in Healthy Adults of African Sub-Saharan Origin.
Clinical and translational scienceRNA Lariat-Debranching Enzyme (DBR1) Variations in Sabinas Brittle Hair Syndrome Form of Trichothiodystrophy: A Trichothiodystrophy-Causing Gene.
The Journal of investigative dermatologyOverlapping upstream ORFs ending at c.125 lead to reduced Endoglin, contributing to Hereditary Hemorrhagic Telangiectasia.
Communications biologyA novel variation in RSPO4 causing nonsyndromic congenital nail disorder-4 in a Chinese patient.
Frontiers in pediatricsCord blood levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 correlate with perinatal brain development in fetal congenital heart disease.
Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and GynecologyGeneration and Characterization of Human Induced Pluripotent Stem Cell-derived Astrocytes Lacking Fragile X Messenger Ribonucleoprotein.
Journal of visualized experiments : JoVEPOLYCYSTIC OVARY SYNDROME: ORIGINS AND IMPLICATIONS: Polycystic ovary syndrome: the impact of androgen excess on metabolic health.
Reproduction (Cambridge, England)Identification of De Novo Chromosomal Translocations Disrupting NIPBL in a Patient With Cornelia de Lange Syndrome by Full Genome Analysis.
Molecular genetics & genomic medicineCargo of small extracellular vesicles from neuronal origin shows progression of dementia in individuals with Down syndrome.
Alzheimer's & dementia : the journal of the Alzheimer's AssociationInvestigating the Origins of Biochemical Dysregulation in Trisomy 21 Pregnancy.
The Journal of clinical endocrinology and metabolismBrain lateralization for perceiving direction of motion is reversed in Williams syndrome and related to BUD23.
Scientific reportsSARS-CoV-2 infection of human cortical cells is influenced by the interaction between aneuploidy and biological sex: insights from a Down syndrome in vitro model.
Acta neuropathologicaGenetic background influences susceptibility to exencephaly in Scavenger receptor Class B type 1-deficient mouse embryos.
PlacentaLymphatic Malformation: Classification, Pathogenesis, and Therapeutic Strategies.
Annals of vascular surgerySequence diversity lost in early pregnancy.
NatureCombining dynamin 2 myopathy and neuropathy mutations rescues both phenotypes.
Nature communicationsScar-associated macrophages and biliary epithelial cells interaction exacerbates hepatic fibrosis in biliary atresia.
Pediatric researchPOLYCYSTIC OVARY SYNDROME: ORIGINS AND IMPLICATIONS: The significance of functional adrenal hyperandrogenism in polycystic ovary syndrome across the lifespan.
Reproduction (Cambridge, England)Management of VACTERL association with uterine anomaly: complex acute on chronic 10-year pelvic pain with haematometra.
BMJ case reportsInterface between reproductive and metabolic dysfunction in polycystic ovary syndrome.
Current opinion in obstetrics & gynecologyMitochondrial Dysfunction: A New Hallmark in Hereditable Thoracic Aortic Aneurysm Development.
CellsUsing chanarin-dorfman syndrome patient fibroblasts to explore disease mechanisms and new treatment avenues.
Orphanet journal of rare diseasesNkx2.7 is a conserved regulator of craniofacial development.
Nature communicationsGenetic requirement for Esrp1/2 in vertebrate pituitary morphogenesis.
medRxiv : the preprint server for health sciencesAlterations in dopaminergic innervation and receptors in focal cortical dysplasia.
Brain : a journal of neurologyEmbryological cellular origins and hypoxia-mediated mechanisms in PIK3CA-driven refractory vascular malformations.
EMBO molecular medicineHomozygous HOXC13 Variant Causes Pure Hair and Nail Ectodermal Dysplasia via Reduction in Protein Stability.
Human mutationCollagen IV of basement membranes: I. Origin and diversification of COL4 genes enabling metazoan multicellularity, evolution, and adaptation.
The Journal of biological chemistryCOG6-related prenatal phenotype (CDG2L): Clinico-pathological report and review of the literature.
Molecular genetics & genomic medicineInhibin B and AMH for Diagnosis of Hypogonadotropic Hypogonadism in Boys Under 1 Year of Age: A Case-control Study.
The Journal of clinical endocrinology and metabolismA differential requirement for ciliary transition zone proteins in human and mouse neural progenitor fate specification.
Nature communicationsClinical yield of esophagogastroduodenoscopy and pH-impedance testing in esophageal atresia patients performed according to international guidelines.
Diseases of the esophagus : official journal of the International Society for Diseases of the EsophagusDynamic single-cell transcriptomic reveals the cellular heterogeneity and a novel fibroblast subpopulation in laryngotracheal stenosis.
Biology directSmith-Lemli-Opitz Syndrome: Oral Characteristics and Risk Factors for Caries Development.
BiomedicinesSox9 in the second heart field and the development of the outflow tract; implications for cardiac septation and valve formation.
Developmental dynamics : an official publication of the American Association of AnatomistsRescue of loss-of-function long QT syndrome-associated mutations in KV7.1/KCNE1 by the endocannabinoid N-arachidonoyl-L-serine (ARA-S).
British journal of pharmacologyPOLYCYSTIC OVARY SYNDROME: ORIGINS AND IMPLICATIONS: Polycystic ovary syndrome: an evolutionary metabolic adaptation.
Reproduction (Cambridge, England)Synaptic-dependent developmental dysconnectivity in 22q11.2 deletion syndrome.
Science advancesImpaired yolk sac NAD metabolism disrupts murine embryogenesis with relevance to human birth defects.
eLife[Integrative transcriptomics-metabolomics approach to identify metabolic pathways regulated by glutamine synthetase activity].
Se pu = Chinese journal of chromatographyA Novel Variant in Dentin Sialophosphoprotein (DSPP) Gene Causes Dentinogenesis Imperfecta Type III: Case Report.
Molecular genetics & genomic medicineIlluminating Cardiac Remodeling: Insights From [18F]-Fluorodeoxyglucose Positron Emission Tomography Imaging in Plakoglobin-Associated Arrhythmogenic Cardiomyopathy.
Journal of the American Heart AssociationFundamental origins of neural tube defects with a basis in genetics and nutrition.
Experimental brain researchA case report of reversible dilated cardiomyopathy due to left main coronary artery ostial stenosis: optimal imaging is key.
European heart journal. Case reportsSynaptic Dysregulation Drives Hyperexcitability in Pyramidal Neurons Surrounding Freeze-Induced Neocortical Malformations in Rats.
International journal of molecular sciencesBone disease and oromaxillofacial disorders: a cross- sectional study in a Tanzanian pediatric population.
Orphanet journal of rare diseasesIdentification of key autophagy-related genes in arrhythmogenic right ventricular cardiomyopathy through gene expression profiling.
MedicineHeart Disease in Children: Cardiac Dysrhythmias.
FP essentialsCell-Free DNA Results Indicating Mosaic Monosomy X of Likely Maternal Origin: Impact on Genetic Counseling Practices and Patient Experiences.
Prenatal diagnosisAssociation of trace element levels in primary teeth and occurrence of Cleft lip and/or palate.
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)Patterns of Increased Cardiomyocyte Ploidy in Myocardial Hypertrophy of Various Origins.
Bulletin of experimental biology and medicinePhenotype and genotype of 23 patients with hypopituitarism and pathogenic GLI2 variants.
European journal of endocrinology[CA 19-9 Secreting Extralobar Sequestration Presenting as a Bifocal Posterior Mediastinal Tumour].
Zentralblatt fur ChirurgiePhenotypical Characterization of Gastroenterological and Metabolic Manifestations in Patients With Williams-Beuren Syndrome.
American journal of medical genetics. Part ASingle-cell transcriptomic profiling of rat iridocorneal angle at perinatal stages: Revisiting the development of periocular mesenchyme.
Experimental eye researchInhibition of aortic CX3CR1+ macrophages mitigates thoracic aortic aneurysm progression in Marfan syndrome in mice.
The Journal of clinical investigationAging Skin: A Dermatitis To Which All Flesh Is Heir?
Journal of cutaneous pathologyThirty years of StAR gazing. Expanding the universe of the steroidogenic acute regulatory protein.
The Journal of endocrinologyRNA-binding proteins in disease etiology: fragile X syndrome and spinal muscular atrophy.
RNA (New York, N.Y.)An extragenital cell population contributes to urethra closure during mouse penis development.
Science advancesAdrenal adenoma secreting 17-hydroxyprogesterone mimicking non-classical 21-hydroxylase deficiency.
Frontiers in endocrinologyAutopsy case of a stillbirth with transient abnormal myelopoiesis associated with Down syndrome: Immunohistochemical demonstration of GATA1 mutation in placental tissues.
Pathology internationalDiagnostic pitfalls in ovarian androgen-secreting tumors in postmenopausal women with rapidly progressed severe hyperandrogenism.
Post reproductive healthCharacterising the lipid profile of paediatric patients with anomalous aortic origins of a coronary artery.
Cardiology in the youngMelanin-like nanoparticles slow cyst growth in ADPKD by dual inhibition of oxidative stress and CREB.
EMBO molecular medicineBrain and behavioural anomalies caused by Tbx1 haploinsufficiency are corrected by vitamin B12.
Life science allianceNon-invasive prenatal detection of dominant single-gene disorders in fetal structural abnormalities: a clinical feasibility study.
Archives of gynecology and obstetricsHyperandrogenism after menopause: diagnostic evaluation.
Climacteric : the journal of the International Menopause SocietyThe role of the co-chaperone DNAJB11 in polycystic kidney disease: Molecular mechanisms and cellular origin of cyst formation.
FASEB journal : official publication of the Federation of American Societies for Experimental BiologyA WFS1 variant disrupting acceptor splice site uncovers the impact of alternative splicing on beta cell apoptosis in a patient with Wolfram syndrome.
DiabetologiaWhole Blood Transcriptome Analysis in Congenital Anemia Patients.
International journal of molecular sciencesProtective role of 2-aminothiazole derivative against ethanol-induced teratogenic effects in-vivo zebrafish.
Biochemical pharmacologyZebrafish arterial valve development occurs through direct differentiation of second heart field progenitors.
Cardiovascular researchSTING Promotes the Progression of ADPKD by Regulating Mitochondrial Function, Inflammation, Fibrosis, and Apoptosis.
BiomoleculesNew functions of B9D2 in tight junctions and epithelial polarity.
Scientific reportsArterial-Lymphatic-Like Endothelial Cells Appear in Hereditary Hemorrhagic Telangiectasia 2 and Contribute to Vascular Leakage and Arteriovenous Malformations.
CirculationThe intricacies of tooth enamel: Embryonic origin, development and human genetics.
Journal of structural biologyRhesus rotavirus NSP1 mediates extra-intestinal infection and is a contributing factor for biliary obstruction.
PLoS pathogensAmyloid precursor protein as a fibrosis marker in infants with biliary atresia.
Pediatric researchKMT2D deficiency leads to cellular developmental disorders and enhancer dysregulation in neural-crest-containing brain organoids.
Science bulletinIncreased susceptibility of human limbal aniridia fibroblasts to oxidative stress.
Experimental eye researchCongenital microcoria deletion in mouse links Sox21 dysregulation to disease and suggests a role for TGFB2 in glaucoma and myopia.
American journal of human geneticsPostoperative Organ Dysfunction Risk Stratification Using Extracellular Vesicle-Derived circRNAs in Pediatric Congenital Heart Surgery.
CellsPerinatal lethal form Gaucher disease with compound heterozygosity of single nucleotide variants and copy number variations presenting as nonimmune hydrops fetalis and cerebellar hypoplasia: A case report.
Taiwanese journal of obstetrics & gynecologyImaging the development of the human craniofacial arterial system - an experimental study.
Pediatric radiologyGain-of-function variants in SMAD4 compromise respiratory epithelial function.
The Journal of allergy and clinical immunologyParent-of-origin-specific DNA replication timing is confined to large imprinted regions.
Cell reports[Clinical phenotype and molecular genetic analysis of seven children with CHARGE syndrome].
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical geneticsPumping the Breaks on Acantholytic Skin Disorders: Targeting Calcium Pumps, Desmosomes, and Downstream Signaling in Darier, Hailey-Hailey, and Grover Disease.
The Journal of investigative dermatologyUpdate on Pediatric Cancer Surveillance Recommendations for Patients with Neurofibromatosis Type 1, Noonan Syndrome, CBL Syndrome, Costello Syndrome, and Related RASopathies.
Clinical cancer research : an official journal of the American Association for Cancer ResearchMolecular basis of urostyle development in frogs: genes and gene regulation underlying an evolutionary novelty.
Open biologyIntegrated prenatal and postnatal management for neonates with transposition of the great arteries: thirteen-year experience at a single center.
Italian journal of pediatricsAssociation of maternal ABO blood type with lesion level and birthweight of children with spina bifida: a descriptive study.
Journal of medicine and lifePlasma 21-deoxycortisone: a sensitive additive tool in 21-hydroxylase deficiency in newborns.
European journal of endocrinologySMAD4 mutations causing Myhre syndrome are under positive selection in the male germline.
American journal of human geneticsMonocentric Study on the Performance of Noninvasive Prenatal Testing on Cell-Free DNA for the Detection of Monosomy X.
Prenatal diagnosisPathophysiological and Pedigree Analysis of Left Ventricular Noncompaction in Japanese Macaques (Macaca fuscata).
Comparative medicineLoss of Elp1 in cerebellar granule cell progenitors models ataxia phenotype of Familial Dysautonomia.
Neurobiology of diseaseHuman cytomegalovirus infection impairs neural differentiation via repressing sterol regulatory element binding protein 2-mediated cholesterol biosynthesis.
Cellular and molecular life sciences : CMLSElectrical Synapses Mediate Embryonic Hyperactivity in a Zebrafish Model of Fragile X Syndrome.
The Journal of neuroscience : the official journal of the Society for NeuroscienceTherapeutic Efficacy of Mexiletine for Long QT Syndrome Type 2: Evidence From Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes, Transgenic Rabbits, and Patients.
CirculationImproved prenatal assessment of kidney disease using multiple ultrasound features.
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal AssociationAnti-Müllerian Hormone: A Molecular Key to Unlocking Polycystic Ovary Syndrome?
Seminars in reproductive medicineJoint effects of CD8A and ICOS in Long QT Syndrome (LQTS) and Beckwith-Wiedemann Syndrome (BWS).
Journal of cardiothoracic surgeryGeneration of three iPSC lines with inducible systems to be used in Angelman syndrome research.
Stem cell researchNovel Compound Heterogeneous Mutations in CYB5R3 Gene Leading to Methemoglobinemia (Type I) in a Chinese Boy: Case Report and Relevant Comprehensive Analysis.
Acta haematologicaTotal osteocalcin levels are independently associated with worse testicular function and a higher degree of hypothalamic-pituitary-gonadal axis activation in Klinefelter syndrome.
Journal of endocrinological investigationHuman iPSC and CRISPR targeted gene knock-in strategy for studying the somatic TIE2L914F mutation in endothelial cells.
AngiogenesisImplication of the endocannabidiome and metabolic pathways in fragile X syndrome pathophysiology.
Psychiatry researchThe hematopoietic microenvironment of the fetal liver and transient abnormal myelopoiesis associated with Down syndrome: A review.
Critical reviews in oncology/hematologyCAVIN1-Mediated hERG Dynamics: A Novel Mechanism Underlying the Interindividual Variability in Drug-Induced Long QT.
CirculationIdentification of a de novo PUF60 variant associated with craniofacial microsomia.
American journal of medical genetics. Part ABLM helicase unwinds lagging strand substrates to assemble the ALT telomere damage response.
Molecular cellTargeting the EGFR pathway: An alternative strategy for the treatment of tuberous sclerosis complex?
Neuropathology and applied neurobiologyFrequent protein kinase A regulatory subunit A1 mutations but no GNAS mutations as potential driver in sporadic cardiac myxomas.
Cardiovascular pathology : the official journal of the Society for Cardiovascular PathologyEnteric Nervous System Striped Patterning and Disease: Unexplored Pathophysiology.
Cellular and molecular gastroenterology and hepatology[Improved Care and Treatment Options for Patients with Hyperphagia-Associated Obesity in Bardet-Biedl Syndrome].
Klinische PadiatrieSingle-cell guided prenatal derivation of primary fetal epithelial organoids from human amniotic and tracheal fluids.
Nature medicineBrain function in classic galactosemia, a galactosemia network (GalNet) members review.
Frontiers in geneticsIntraoperative ECoG in bottom-of-the-sulcus syndrome using a novel flexible strip electrode.
Epileptic disorders : international epilepsy journal with videotapeLoss of GTF2I promotes neuronal apoptosis and synaptic reduction in human cellular models of neurodevelopment.
Cell reportsFurther Delineation of Clinical Phenotype of ZMYND11 Variants in Patients with Neurodevelopmental Dysmorphic Syndrome.
GenesPsychotic illness in people with Prader-Willi syndrome: a systematic review of clinical presentation, course and phenomenology.
Orphanet journal of rare diseasesThe Cyst Epithelium in Polycystic Kidney Disease Patients Displays Normal Apical-Basolateral Cell Polarity.
International journal of molecular sciencesAromatase deficiency in transplanted bone marrow cells improves vertebral trabecular bone quantity, connectivity, and mineralization and decreases cortical porosity in murine bone marrow transplant recipients.
PloS oneAlteration of actin cytoskeletal organisation in fetal akinesia deformation sequence.
Scientific reportsUnderstanding the cell fate and behavior of progenitors at the origin of the mouse cardiac mitral valve.
Developmental cellDiscovery of novel diagnostic biomarkers for Sjögren-Larsson syndrome by untargeted lipidomics.
Biochimica et biophysica acta. Molecular and cell biology of lipidsQuantitative Characterization of Ectopic Adrenal Gene Expression in Fetal Testes in 21-Hydroxylase Deficient Mice.
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolismeModulating inflammation with interleukin 37 treatment ameliorates murine Autosomal Dominant Polycystic Kidney Disease.
Kidney internationalAndrogen excess: a hallmark of polycystic ovary syndrome.
Frontiers in endocrinologyA lissencephaly-associated BAIAP2 variant causes defects in neuronal migration during brain development.
Development (Cambridge, England)Hyperactive mTORC1 in lung mesenchyme induces endothelial cell dysfunction and pulmonary vascular remodeling.
The Journal of clinical investigationThe rare malformation holoprosencephaly: pathogenesis, association with pregestational diabetes and the possible link with food pollutants.
Annali dell'Istituto superiore di sanitaSex-Specific Perturbation of Systemic Lipidomic Profile in Newborn Lambs Impacted by Prenatal Testosterone Excess.
EndocrinologyNovel Ameloblastin Variants, Contrasting Amelogenesis Imperfecta Phenotypes.
Journal of dental researchThioredoxin Reductase 2 Variant as a Cause of Micropenis, Undescended Testis, and Selective Glucocorticoid Deficiency.
Hormone research in paediatricsMaternal Pre-Existing Diabetes: A Non-Inherited Risk Factor for Congenital Cardiopathies.
International journal of molecular sciencesEmbryonic exposure to decitabine induces multiple neural tube defects in developing zebrafish.
Fish physiology and biochemistrySkeletal defects and bone metabolism in Noonan, Costello and cardio-facio-cutaneous syndromes.
Frontiers in endocrinologyInfluence of genetics on the occurrence of enamel hypomineralization affecting permanent and primary teeth: A scoping review.
International journal of paediatric dentistryDMRT1 is a testis-determining gene in rabbits and is also essential for female fertility.
eLifeCLDN1 Arg81His founder variant causes ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis (ILVASC) syndrome in Moroccan Jews.
Clinical geneticsEpigenomic signature of major congenital heart defects in newborns with Down syndrome.
Human genomicsMimicking Hypoxic-Ischemic Encephalopathy in a Newborn with 21q Deletion Originating from Ring Chromosome 21.
Children (Basel, Switzerland)[Genetic analysis of a child with Meier-Gorlin syndrome due to a variant of ORC6 gene].
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical geneticsDisruption of TUFT1, a Desmosome-Associated Protein, Causes Skin Fragility, Woolly Hair, and Palmoplantar Keratoderma.
The Journal of investigative dermatologyBiallelic truncating variants in VGLL2 cause syngnathia in humans.
Journal of medical geneticsAssociações
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Doença com base genética
Um médico geneticista pode ajudar no diagnóstico de Síndrome dismórfico de origem metabólica e no aconselhamento genético da família.
Doenças relacionadas
Doenças com sintomas parecidos — ajudam quem ainda está buscando diagnóstico
Perguntas frequentes
O que as famílias mais perguntam sobre esta doença — cada resposta com a fonte de onde saiu
A condição decorre de alterações em vias metabólicas causadas por variantes em genes como FH, NDUFV2, PIGL, MECR, entre outros. Esses genes codificam enzimas essenciais para o funcionamento celular e para o desenvolvimento durante a formação do organismo.
Referências
Fontes citadas no texto, publicações do grafo e bases de dados usadas neste verbete
4 fontes citadas no texto · 5 publicações do grafo RarasNet (PubMed) · 4 bases de dados. Títulos, periódicos e PMIDs vêm direto da fonte, sem intermediação de IA.
Dados compilados pelo RarasNet a partir de fontes abertas (Orphanet, OMIM, MONDO, PubMed/EuropePMC, ClinicalTrials.gov, DATASUS, PCDT/MS). Este conteúdo é informativo e não substitui avaliação médica.
Citar este verbete
Raras. (2026). Síndrome dismórfico de origem metabólica. Em Raras — Enciclopédia de Doenças Raras do Brasil. https://raras.org/doenca/sindrome-dismorfico-de-origem-metabolica
Formato APA. Conteúdo sob CC BY 4.0 — reuso livre com atribuição.
Conteúdo mantido por Agente Raras · Médicos e pesquisadores podem colaborar
Síndrome dismórfico de origem metabólica
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Esta página agrega dados de fontes públicas e oficiais. Dados sobre cobertura no SUS (PCDT, CEAF) são verificados ativamente por agente proativo (ver badge no infobox). Demais dados têm atribuição de fonte + data da última sincronização — clique para abrir o original.
- Doença rara (ontologia)
- fonte: Orphanet
- Identificador unificado
- fonte: MONDO
- NIH/GARD
- fonte: GARD (NIH)
- Dado público estruturado
- fonte: Wikidata
- Moléculas estudadas na doença
- fonte: OpenTargets
