A célula é a unidade estrutural e funcional básica de todas as formas de vida ou organismos. O termo vem da palavra latina cellula, que significa "pequeno compartimento". Uma célula biológica consiste basicamente em uma membrana celular semipermeável que envolve o citoplasma, o qual contém material genético. A maioria das células só é visível sob um microscópio. Com exceção de tipos celulares altamente diferenciados, a maioria das células é capaz de replicação e síntese proteica. Alguns tipos de células são móveis.
Introdução
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Visão geral
As ciliopatias com envolvimento esquelético extenso são um grupo de doenças genéticas raras que afetam o funcionamento dos cílios, estruturas microscópicas presentes em diversas células do corpo. Essas condições são caracterizadas por alterações ósseas significativas, que podem incluir tórax estreito (hipoplasia torácica), dedos curtos e unhas dos pés com formato anormal. Por ser um grupo de doenças, a apresentação e a gravidade podem variar bastante de pessoa para pessoa.[1][2]
Sinais e sintomas
Os sinais e sintomas das ciliopatias com envolvimento esquelético extenso são variados e podem afetar múltiplos sistemas do corpo. Entre os achados esqueléticos mais comuns estão a hipoplasia torácica (tórax estreito), dedos curtos, polidactilia pré-axial (dedo extra na parte de dentro da mão ou do pé), camptodactilia (dedo permanentemente fletido), dedo do pé sobreposto e alterações na pelve, como o acetábulo em tridente e o serrilhado da crista ilíaca. Além disso, podem ocorrer retrusão médio-facial (face com aparência de “afundada” no meio) e crista metópica proeminente (saliência na testa).[1][2]
Outros sintomas podem incluir dificuldades alimentares, atraso no desenvolvimento motor (como habilidade atrasada para sentar), problemas de visão (acuidade visual reduzida e atenuação dos vasos sanguíneos da retina), anomalias renais (hiperecogenicidade cortical renal), alterações hepáticas (malformação da placa ductal hepática e ausência de vesícula biliar), sinusite crônica, estenose da artéria pulmonar periférica, anomalia de Duane (um tipo de estrabismo), orelhas de formato simples, atrofia cerebral subcortical, hipocelularidade da medula óssea, tamanho testicular diminuído e motilidade espermática reduzida.[1][2]
Causas genéticas
As ciliopatias com envolvimento esquelético extenso são causadas por alterações (mutações) em genes que codificam proteínas essenciais para a estrutura e função dos cílios. Os genes já identificados incluem: WDR35, TTC21B, IFT80, IFT140, IFT43, WDR19, DYNC2I1, TRAF3IP1, EVC, TCTN3, IFT81 e CSPP1. Cada um desses genes fornece instruções para a produção de proteínas que participam do transporte intraflagelar, um processo fundamental para a montagem e manutenção dos cílios.[1][3]
Diagnóstico
O diagnóstico das ciliopatias com envolvimento esquelético extenso é baseado na avaliação clínica dos sinais e sintomas, exames de imagem (como radiografias para identificar as alterações ósseas características) e, principalmente, por meio de testes genéticos. Atualmente, existem 336 testes genéticos disponíveis para investigar mutações nos genes associados a essas condições. O banco de dados ClinVar já registrou 560 variantes genéticas diferentes relacionadas a essas doenças, o que auxilia na confirmação diagnóstica.[1][3]
Tratamento e manejo
Não existe um tratamento específico que cure as ciliopatias com envolvimento esquelético extenso. O manejo é multidisciplinar e focado no alívio dos sintomas e na melhora da qualidade de vida. Pode incluir acompanhamento com ortopedista para as alterações ósseas, fisioterapia para atrasos motores, suporte nutricional para dificuldades alimentares, tratamento para sinusite crônica e acompanhamento oftalmológico para problemas de visão. Cada caso deve ser avaliado individualmente por uma equipe médica especializada.[1]
Prognóstico e qualidade de vida
O prognóstico das ciliopatias com envolvimento esquelético extenso varia amplamente, dependendo da gravidade das manifestações em cada pessoa. O acompanhamento regular com uma equipe multidisciplinar é fundamental para identificar e tratar precocemente as complicações, visando melhorar a qualidade de vida e o bem-estar do paciente e de sua família.[1]
Conteúdo informativo gerado e mantido automaticamente a partir de fontes oficiais (Orphanet, HPO, OMIM, SUS). Não substitui avaliação médica.
As ciliopatias com envolvimento esquelético extenso formam um grupo de condições raras que alteram o desenvolvimento dos ossos e do tórax. A família pode notar alterações nas mãos, pés e formato do tórax, além de possíveis dificuldades alimentares ou atraso para sentar. A doença pode também comprometer outros órgãos vitais, como os rins, o fígado e a visão. Não há remédio curativo específico e a condição não consta na lista oficial de PCDTs de doenças raras do Ministério da Saúde. O cuidado é focado em aliviar os sintomas e acompanhar o desenvolvimento da criança pela rede de saúde.
A célula é a unidade estrutural e funcional básica de todas as formas de vida ou organismos. O termo vem da palavra latina cellula, que significa "pequeno compartimento". Uma célula biológica consiste basicamente em uma membrana celular semipermeável que envolve o citoplasma, o qual contém material genético. A maioria das células só é visível sob um microscópio. Com exceção de tipos celulares altamente diferenciados, a maioria das células é capaz de replicação e síntese proteica. Alguns tipos de células são móveis.
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Sinais e sintomas
O que aparece no corpo e com que frequência cada sintoma acontece
Partes do corpo afetadas
+ 254 sintomas em outras categorias
Características mais comuns
Os sintomas variam de pessoa para pessoa. Abaixo estão as 646 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
30 genes identificados com associação a esta condição.
Cranioectodermal dysplasia 2
A disorder characterized by craniofacial, skeletal and ectodermal abnormalities. Clinical features include short stature, dolichocephaly, craniosynostosis, narrow thorax with pectus excavatum, short limbs, brachydactyly, joint laxity, narrow palpebral fissures, telecanthus with hypertelorism, low-set simple ears, everted lower lip, and short neck. Teeth abnormalities include widely spaced, hypoplastic and fused teeth.
Short-rib thoracic dysplasia 2 with or without polydactyly
A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome.
Short-rib thoracic dysplasia 9 with or without polydactyly
A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome. SRTD9 is characterized by phalangeal cone-shaped epiphyses, chronic renal disease, nearly constant retinal dystrophy, and mild radiographic abnormality of the proximal femur. Occasional features include short stature, cerebellar ataxia, and hepatic fibrosis.
Cranioectodermal dysplasia 3
A disorder primarily characterized by craniofacial, skeletal and ectodermal abnormalities. Clinical features include craniosynostosis, narrow rib cage, short limbs, brachydactyly, hypoplastic and widely spaced teeth, sparse hair, skin laxity and abnormal nails. Nephronophthisis leading to progressive renal failure, hepatic fibrosis, heart defects, and retinitis pigmentosa have also been described.
Cranioectodermal dysplasia 4
A disorder primarily characterized by craniofacial, skeletal and ectodermal abnormalities. Clinical features include craniosynostosis, narrow rib cage, short limbs, brachydactyly, hypoplastic and widely spaced teeth, sparse hair, skin laxity and abnormal nails. Nephronophthisis leading to progressive renal failure, hepatic fibrosis, heart defects, and retinitis pigmentosa have also been described.
Short-rib thoracic dysplasia 8 with or without polydactyly
A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome.
Senior-Loken syndrome 9
A renal-retinal disorder characterized by progressive wasting of the filtering unit of the kidney (nephronophthisis), with or without medullary cystic renal disease, and progressive eye disease. Typically this disorder becomes apparent during the first year of life.
Ellis-van Creveld syndrome
An autosomal recessive condition characterized by the clinical tetrad of chondrodystrophy, polydactyly, ectodermal dysplasia and cardiac anomalies. Patients manifest short-limb dwarfism, short ribs, postaxial polydactyly, and dysplastic nails and teeth. Congenital heart defects, most commonly an atrioventricular septal defect, are observed in 60% of affected individuals.
Orofaciodigital syndrome 4
A form of orofaciodigital syndrome, a group of heterogeneous disorders characterized by malformations of the oral cavity, face and digits, and associated phenotypic abnormalities that lead to the delineation of various subtypes. OFD4 patients have tongue nodules, multiple frenulae, broad flat nose, hypertelorism, and short rib polydactyly with tibial dysplasia (Majewski syndrome). The presence of severe tibial aplasia differentiates OFD4 from OFD1. Additional features of cystic dysplastic kidneys and brain malformation, including occipital encephalocele, are observed in severely affected patients.
Short-rib thoracic dysplasia 19 with or without polydactyly
A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome.
Joubert syndrome 21
A disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly.
Short-rib thoracic dysplasia 16 with or without polydactyly
A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome.
Primary pigmented nodular adrenocortical disease 4
A rare bilateral adrenal defect causing ACTH-independent Cushing syndrome. Macroscopic appearance of the adrenals is characteristic with small pigmented micronodules observed in the cortex. Adrenal glands show overall normal size and weight, and multiple small yellow-to-dark brown nodules surrounded by a cortex with a uniform appearance. Microscopically, there are moderate diffuse cortical hyperplasia with mostly nonpigmented nodules, multiple capsular deficits and massive circumscribed and infiltrating extra-adrenal cortical excrescences with micronodules. Clinical manifestations of Cushing syndrome include facial and truncal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes.
Short-rib thoracic dysplasia 13 with or without polydactyly
A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome.
Polydactyly, postaxial, A8
A form of postaxial polydactyly, a condition characterized by the occurrence of supernumerary digits in the upper and/or lower extremities. In postaxial polydactyly type A, the extra digit is well-formed and articulates with the fifth or a sixth metacarpal/metatarsal. PAPA8 is an autosomal recessive condition characterized by the presence of postaxial extra digits (hexadactyly) on the hands and/or the feet.
Joubert syndrome 23
A mild form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly.
Short-rib thoracic dysplasia 15 with polydactyly
A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome.
Short-rib thoracic dysplasia 17 with or without polydactyly
A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome.
Short-rib thoracic dysplasia 11 with or without polydactyly
A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome.
Short-rib thoracic dysplasia 6 with or without polydactyly
A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome.
Short-rib thoracic dysplasia 3 with or without polydactyly
A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome.
Ellis-van Creveld syndrome
An autosomal recessive condition characterized by the clinical tetrad of chondrodystrophy, polydactyly, ectodermal dysplasia and cardiac anomalies. Patients manifest short-limb dwarfism, short ribs, postaxial polydactyly, and dysplastic nails and teeth. Congenital heart defects, most commonly an atrioventricular septal defect, are observed in 60% of affected individuals.
Lethal congenital contracture syndrome 10
A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy and congenital non-progressive joint contractures. The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth.
Short-rib thoracic dysplasia 10 with or without polydactyly
A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome.
Retinal dystrophy with or without macular staphyloma
An ocular disorder characterized by decreased vision which worsen over time, and dystrophic changes in the retina, such as retinal pigment epithelium mottling and vessel narrowing. Macular staphyloma, without high myopia, is present in some patients.
Orofaciodigital syndrome 15
A form of orofaciodigital syndrome, a group of heterogeneous disorders characterized by malformations of the oral cavity, face and digits, and associated phenotypic abnormalities that lead to the delineation of various subtypes. OFD15 features include facial dysmorphism, lobulated tongue, clefting of the alveolar ridges, left hand postaxial polydactyly, broad right hallux and left hallux duplication, and intermittent respiratory difficulty. Brain anomalies include vermis hypoplasia with molar tooth sign, agenesis of corpus callosum, and ventricular dilation. OFD15 inheritance is autosomal recessive.
Short-rib thoracic dysplasia 20 with polydactyly
A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome.
Cardioacrofacial dysplasia 2
An autosomal dominant disease characterized by dysmorphic facial features, congenital cardiac defects, primarily common atrium or atrioventricular septal defect, and limb anomalies, including short limbs, brachydactyly and postaxial polydactyly. CAFD2 patients may show developmental delay of variable severity, intellectual disability, autistic features and focal seizures.
Cranioectodermal dysplasia 1
A disorder characterized by craniofacial, skeletal and ectodermal abnormalities. Clinical features include dolichocephaly (with or without sagittal suture synostosis), scaphocephaly, short stature, limb shortening, short ribs, narrow chest, brachydactyly, renal failure and hepatic fibrosis, small and abnormally shaped teeth, sparse hair, skin laxity and abnormal nails.
Variantes genéticas (ClinVar)
560 variantes patogênicas registradas no ClinVar.
Vias biológicas (Reactome)
44 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 — Ciliopatias com envolvimento esquelético extenso
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Pesquisa ativa
Ensaios clínicos abertos e novidades científicas recentes
Pesquisa e ensaios clínicos
Nenhum ensaio clínico registrado para esta condição.
Publicações mais relevantes
Retinal astrocytoma and Jeune syndrome relationship from ciliopathy perspective: a case report.
Jeune syndrome is an autosomal recessive chondrodysplasia characterized by skeletal deformities and extra-skeletal organ involvement. Retinal astrocytic hamartomas (astrocytomas) are benign glial cell 10 15 Q1 tumors that are generally asymptomatic and diagnosed incidentally. The IFT74 gene is responsible for the formation of IFT proteins, which play a major role in ciliogenesis. In this retrospective clinical laboratory observational study, an 18-year-old male with Jeune syndrome and night vision loss is presented. Fundus examination revealed bilateral optic discs with minimally blurred margins and bilateral retinal pigment epithelium changes in salt-pepper pattern in the peripheral retina. Additionally, a yellowish retinal astrocytoma was observed inferior to the optic disc in the left eye. Genetic analysis of the patient revealed a homozygous deletion in exon 2 of the IFT74 gene. Our observations on this patient and some relationships between hamartoma and ciliopathies other than eye may potentially suggest a possible association between Jeune syndrome and retinal astrocytoma in the context of IFT74-related ciliopathies.
Reanalysis of Whole-Exome Sequencing Data of an Infant with Suspected Diagnosis of Jeune Syndrome Revealed a Likely Pathogenic Variant in GRK2: A Newly Associated Gene for Jeune Syndrome Phenotype.
Ciliopathies with major skeletal involvement embrace a group of heterogeneous disorders caused by pathogenic variants in a group of diverse genes. A narrow thorax with shortening of long bones inspires a clinical entity underlined by dysfunction of primary cilia. Currently, more than 23 genes are listed in the OMIM database corresponding to this clinical entity: WDR19/34/35/60, IFT43/52/80/81/140/172, DYNC2LI1, TTC21B, DYNLT2B, EVC2, EVC, INTU, NEK1, CEP120, DYNC2H1, KIAA0586, SRTD1, KIAA0753, and SRTD12. Recently, individuals with biallelic loss-of-function variants in GRK2 are shown to demonstrate a phenotype compatible with Jeune syndrome. Experimental evidence has shown that impaired function of GRK2 compromises cilia-based signaling of Hedgehog pathway as well as Wnt signaling, while cilia morphology remains intact. Hence, GRK2 is now considered an essential protein in regulation of the skeletogenesis. We presented a female infant born to a consanguineous marriage who was found to have a biallelic p.R474* alteration in GRK2 in reanalysis of the whole-exome sequencing (WES) data. The patient was exhibiting major clinical features of Jeune syndrome, such as shortened long bones, ribs, and narrow thorax. Our reanalysis of WES data revealed a likely pathogenic biallelic variant in the GRK2 which is probably responsible for the Jeune syndrome phenotype in the patient. Hence, our report supports the recently discovered association of GRK2 loss-of-function variants with Jeune syndrome phenotype and emphasizes the significance of reanalysis of WES data, notably in patients with phenotypes suggestive of a such discernible Mendelian disorder.
The genetic landscape and clinical spectrum of nephronophthisis and related ciliopathies.
Nephronophthisis (NPH) is an autosomal-recessive ciliopathy representing one of the most frequent causes of kidney failure in childhood characterized by a broad clinical and genetic heterogeneity. Applied to one of the worldwide largest cohorts of patients with NPH, genetic analysis encompassing targeted and whole exome sequencing identified disease-causing variants in 600 patients from 496 families with a detection rate of 71%. Of 788 pathogenic variants, 40 known ciliopathy genes were identified. However, the majority of patients (53%) bore biallelic pathogenic variants in NPHP1. NPH-causing gene alterations affected all ciliary modules defined by structural and/or functional subdomains. Seventy six percent of these patients had progressed to kidney failure, of which 18% had an infantile form (under five years) and harbored variants affecting the Inversin compartment or intraflagellar transport complex A. Forty eight percent of patients showed a juvenile (5-15 years) and 34% a late-onset disease (over 15 years), the latter mostly carrying variants belonging to the Transition Zone module. Furthermore, while more than 85% of patients with an infantile form presented with extra-kidney manifestations, it only concerned half of juvenile and late onset cases. Eye involvement represented a predominant feature, followed by cerebellar hypoplasia and other brain abnormalities, liver and skeletal defects. The phenotypic variability was in a large part associated with mutation types, genes and corresponding ciliary modules with hypomorphic variants in ciliary genes playing a role in early steps of ciliogenesis associated with juvenile-to-late onset NPH forms. Thus, our data confirm a considerable proportion of late-onset NPH suggesting an underdiagnosis in adult chronic kidney disease. Cranioectodermal dysplasia (CED) is a ciliopathy with skeletal involvement (narrow thorax, shortened proximal limbs, syndactyly, polydactyly, brachydactyly), ectodermal features (widely spaced hypoplastic teeth, hypodontia, sparse hair, skin laxity, abnormal nails), joint laxity, growth deficiency, and characteristic facial features (frontal bossing, low-set simple ears, high forehead, telecanthus, epicanthal folds, full cheeks, everted lower lip). Most affected children develop nephronophthisis that often leads to end-stage kidney disease in infancy or childhood, a major cause of morbidity and mortality. Hepatic fibrosis and retinal dystrophy are also observed. Dolichocephaly, often secondary to sagittal craniosynostosis, is a primary manifestation that distinguishes CED from most other ciliopathies. Brain malformations and developmental delay may also occur. The diagnosis of CED is established in a proband with characteristic clinical and radiographic features (including two frequent features and two other abnormalities, with at least one ectodermal defect – i.e., involvement of the teeth, hair, or nails) and/or by identification of biallelic pathogenic variants in one of the six genes currently known to be associated with CED: IFT43, IFT52, IFT122, IFT140, WDR19, or WDR35. Treatment of manifestations: As needed, surgery to correct sagittal craniosynostosis usually before age one year. Surgical correction may be needed for polydactyly of the hands and feet. Orthopedic care for hip dysplasia. Human growth hormone therapy could be considered in those who meet standard treatment criteria. Standard treatment for dental anomalies, nephronophthisis, liver disease, cardiac anomalies, and/or inguinal and umbilical hernias. For those with progressive visual impairment: low-vision aids and appropriate educational programs. Mechanical ventilation may be required in newborns with pulmonary hypoplasia. For those with developmental delay, speech and physical therapy and appropriate educational programs. Surveillance: In infancy and childhood: monitor tooth development; morning urine osmolarity testing, urine collection assay for polyuria, blood pressure, serum creatinine and blood urea assessment, and renal ultrasound as recommended by nephrologist; hepatic transaminases and measurement of synthetic liver function as recommended by hepatologist. Annual ophthalmologic examinations starting at age four years to detect early signs of retinal degeneration. Cardiac examinations, EKG, and echocardiography per cardiologist. Review of developmental progress at each primary care visit, and formal evaluation with neuropsychological testing if delays noted. CED is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a CED-causing pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing are possible once the CED-causing pathogenic variants have been identified in an affected family member. Second-trimester ultrasound examination may detect renal cysts, shortening of the limbs, and/or polydactyly.
Ellis-Van Creveld Syndrome: Clinical and Molecular Analysis of 50 Individuals.
Ellis-Van Creveld (EVC) syndrome is one of the entities belonging to the skeletal ciliopathies short rib-polydactyly subgroup. Major signs are ectodermal dysplasia, chondrodysplasia, polydactyly and congenital cardiopathy, with a high degree of variability in phenotypes ranging from lethal to mild clinical presentations. The EVC and EVC2 genes are the major genes causative of EVC syndrome. However, an increased number of genes involved in the ciliopathy complex have been identified in EVC syndrome, leading to a better understanding of its physiopathology, namely, WDR35, GLI1, DYNC2LI1, PRKACA, PRKACB and SMO. They all code for proteins located in the primary cilia, playing a key role in signal transduction of the Hedgehog pathways. The aim of this study was the analysis of 50 clinically identified EVC cases from 45 families to further define the phenotype and molecular bases of EVC. Our detection rate in the cohort of 45 families was of 91.11%, with variants identified in EVC/EVC2 (77.8%), DYNC2H1 (6.7%), DYNC2LI1 (2.2%), SMO (2.2%) or PRKACB (2.2%). No distinctive feature was remarkable of a specific genotype-phenotype correlation. Interestingly, we identified a high proportion of heterozygous deletions in EVC/EVC2 of variable sizes (26.92%), mostly inherited from the mother, and probably resulting from recombinations involving Alu sequences. We confirmed that EVC and EVC2 are the major genes involved in the EVC phenotype and highlighted the high prevalence of previously unreported CNVs (Copy Number Variation).
Prenatal Diagnosis of Jeune Syndrome Caused by Compound Heterozygous Variants in DYNC2H1 Gene-Case Report with Rapid WES Procedure and Differential Diagnosis of Lethal Skeletal Dysplasias.
Skeletal dysplasias (SDs) are a large, heterogeneous group of mostly genetic disorders that affect the bones and cartilage, resulting in abnormal growth and development of skeletal structures. The high clinical and genetic diversity in SDs cause difficulties in prenatal diagnosis. To establish a correct prognosis and better management, it is very important to distinguish SDs with poor life-limiting prognosis or lethal SDs from other ones. Bad prognosis in foetuses is assessed on the basis of the size of the thorax, lung volumes, long bones’ length, bones’ echogenicity, bones’ angulation or presented fractures, and the concomitant presence of non-immune hydrops or visceral abnormalities. To confirm SD diagnosis and perform family genetic consultation, rapid molecular diagnostics are needed; therefore, the NGS method using a panel of genes corresponding to SD or whole-exome sequencing (WES) is commonly used. We report a case of a foetus showing long bones’ shortening and a narrow chest with short ribs, diagnosed prenatally with asphyxiating thoracic dystrophy, also known as Jeune syndrome (ATD; OMIM 208500), caused by compound heterozygous variants in the DYNC2H1 gene, identified by prenatally performed rapid-WES analysis. The missense variants in the DYNC2H1 gene were inherited from the mother (c.7289T>C; p.Ile2430Thr) and from the father (c.12716T>G; p.Leu4239Arg). The DYNC2H1 gene is one of at least 17 ATD-associated genes. This disorder belongs to the ninth group of SD, ciliopathies with major skeletal involvement. An extremely narrow, bell-shaped chest, and abnormalities of the kidneys, liver, and retinas were observed in most cases of ATD. Next to lethal and severe forms, clinically mild forms have also been reported. A diagnosis of ATD is important to establish the prognosis and management for the patient, as well as the recurrence risk for the family.
📚 EuropePMCmostrando 12
Retinal astrocytoma and Jeune syndrome relationship from ciliopathy perspective: a case report.
Ophthalmic geneticsReanalysis of Whole-Exome Sequencing Data of an Infant with Suspected Diagnosis of Jeune Syndrome Revealed a Likely Pathogenic Variant in GRK2: A Newly Associated Gene for Jeune Syndrome Phenotype.
Molecular syndromologyThe genetic landscape and clinical spectrum of nephronophthisis and related ciliopathies.
Kidney internationalEllis-Van Creveld Syndrome: Clinical and Molecular Analysis of 50 Individuals.
Journal of medical geneticsPrenatal Diagnosis of Jeune Syndrome Caused by Compound Heterozygous Variants in DYNC2H1 Gene-Case Report with Rapid WES Procedure and Differential Diagnosis of Lethal Skeletal Dysplasias.
GenesPrenatal features and neonatal management of severe hyperparathyroidism caused by the heterozygous inactivating calcium-sensing receptor variant, Arg185Gln: A case report and review of the literature.
Bone reportsPhenotype and genotype spectra of a Chinese cohort with nephronophthisis-related ciliopathy.
Journal of medical geneticsA new case of KIAA0753-related variant of Jeune asphyxiating thoracic dystrophy.
European journal of medical geneticsFunctional characterization of tektin-1 in motile cilia and evidence for TEKT1 as a new candidate gene for motile ciliopathies.
Human molecular geneticsPartial uniparental isodisomy of chromosome 16 unmasks a deleterious biallelic mutation in IFT140 that causes Mainzer-Saldino syndrome.
Human genomicsBeemer-Langer syndrome is a ciliopathy due to biallelic mutations in IFT122.
American journal of medical genetics. Part AMotile and non-motile cilia in human pathology: from function to phenotypes.
The Journal of pathologyAssociações
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Doença com base genética
Um médico geneticista pode ajudar no diagnóstico de Ciliopatias com envolvimento esquelético extenso 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 está associada a mutações em múltiplos genes ligados à função dos cílios celulares, incluindo WDR35, TTC21B, IFT80, IFT140 e WDR19. Essas alterações genéticas afetam a formação esquelética e o desenvolvimento de órgãos.
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). Ciliopatias com envolvimento esquelético extenso. Em Raras — Enciclopédia de Doenças Raras do Brasil. https://raras.org/doenca/ciliopatias-com-envolvimento-esqueletico-extenso
Formato APA. Conteúdo sob CC BY 4.0 — reuso livre com atribuição.
Conteúdo mantido por Agente Raras · Médicos e pesquisadores podem colaborar
Ciliopatias com envolvimento esquelético extenso
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