Majeed syndrome

An autosomal recessive syndrome characterized by chronic recurrent multifocal osteomyelitis that is of early onset with a lifelong course, congenital dyserythropoietic anemia that presents as hypochromic, microcytic anemia during the first year of life and ranges from mild to transfusion-dependent, and transient inflammatory dermatosis, often manifesting as Sweet syndrome (neutrophilic skin infiltration).

Factor XII deficiency

An asymptomatic anomaly of in vitro blood coagulation. Its diagnosis is based on finding a low plasma activity of the factor in coagulating assays. It is usually only accidentally discovered through pre-operative blood tests. Factor XII deficiency is divided into two categories, a cross-reacting material (CRM)-negative group (negative F12 antigen detection) and a CRM-positive group (positive F12 antigen detection).

Juvenile arthritis

A rare, familial form of juvenile arthritis characterized by autosomal recessive inheritance and onset in early childhood of symmetric, chronic joint inflammation. It causes joint swelling, pain, stiffness and restricted joint movement. JUVAR has high clinical variability. Some patients exhibit systemic symptoms, including quotidian fever, erythematous rash, generalized lymphadenopathy, hepatomegaly, and/or splenomegaly. Others display polyarthritis without systemic inflammation.

Autoinflammatory disease, multisystem, with immune dysregulation, X-linked

An X-linked recessive disorder apparent in infancy or early childhood, and characterized by immune dysregulation, variable cytopenias, and systemic or organ-specific autoinflammatory manifestations. Clinical features include systemic lupus erythematosus, panniculitis, inflammatory bowel disease, pulmonary disease, or arthritis associated with recurrent fever, leukocytosis, lymphoproliferation, and hepatosplenomegaly in the absence of an infectious agent. Death in childhood has been reported.

Takenouchi-Kosaki syndrome

An autosomal dominant syndrome characterized by macrothrombocytopenia, lymphedema, intellectual disability, developmental delay, and distinctive facial features.

Ataxia-pancytopenia syndrome

An autosomal dominant disorder characterized by cerebellar ataxia, variable hematologic cytopenias, and predisposition to bone marrow failure and myeloid leukemia.

Polyglucosan body myopathy 1 with or without immunodeficiency

A disease characterized by polyglucosan storage myopathy associated with early-onset progressive muscle weakness and progressive dilated cardiomyopathy, which may necessitate cardiac transplant in severe cases. Some patients present with severe immunodeficiency, invasive bacterial infections and chronic autoinflammation.

Acne inversa, familial, 1

A chronic relapsing inflammatory disease of the hair follicles characterized by recurrent draining sinuses, painful skin abscesses, and disfiguring scars. Manifestations typically appear after puberty.

Aicardi-Goutieres syndrome 2

A form of Aicardi-Goutieres syndrome, a genetically heterogeneous disease characterized by cerebral atrophy, leukoencephalopathy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infection. Clinical features as thrombocytopenia, hepatosplenomegaly and elevated hepatic transaminases along with intermittent fever may erroneously suggest an infective process. Severe neurological dysfunctions manifest in infancy as progressive microcephaly, spasticity, dystonic posturing and profound psychomotor retardation. Death often occurs in early childhood.

Sarcoidosis 2

An idiopathic, systemic, inflammatory disease characterized by the formation of immune granulomas in involved organs. Granulomas predominantly invade the lungs and the lymphatic system, but also skin, liver, spleen, eyes and other organs may be involved.

Psoriasis 15, pustular

A form of pustular psoriasis, a life-threatening disease defined by repeated flares of sudden onset consisting of diffuse erythematous skin eruption characterized by rapid coverage with pustules, high-grade fever, asthenia, marked leukocytosis, and elevated serum levels of C-reactive protein.

Persistent Muellerian duct syndrome 1

A form of male pseudohermaphroditism characterized by a failure of Muellerian duct regression in otherwise normal males.

Immunodeficiency 115 with autoinflammation

An autosomal recessive immunologic disorder manifesting in early infancy and characterized by combined immunodeficiency, recurrent bacterial, viral, and fungal infections, as well as autoinflammatory features, including arthritis and dermatitis.

Aicardi-Goutieres syndrome 3

A form of Aicardi-Goutieres syndrome, a genetically heterogeneous disease characterized by cerebral atrophy, leukoencephalopathy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infection. Clinical features as thrombocytopenia, hepatosplenomegaly and elevated hepatic transaminases along with intermittent fever may erroneously suggest an infective process. Severe neurological dysfunctions manifest in infancy as progressive microcephaly, spasticity, dystonic posturing and profound psychomotor retardation. Death often occurs in early childhood.

Specific granule deficiency 1

An immunologic disorder characterized by recurrent pyogenic infections, defective neutrophil chemotaxis and bactericidal activity, and lack of neutrophil secondary granule proteins. Neutrophils of affected individuals lack lactoferrin and show abnormal nuclear segmentation, bilobed nuclei, low alkaline phosphatase, and increased number of neutrophil mitochondria and ribosomes. SGD1 inheritance can be autosomal dominant or recessive.

Aicardi-Goutieres syndrome 5

A form of Aicardi-Goutieres syndrome, a genetically heterogeneous disease characterized by cerebral atrophy, leukoencephalopathy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infection. Clinical features as thrombocytopenia, hepatosplenomegaly and elevated hepatic transaminases along with intermittent fever may erroneously suggest an infective process. Severe neurological dysfunctions manifest in infancy as progressive microcephaly, spasticity, dystonic posturing and profound psychomotor retardation. Death often occurs in early childhood.

Autoinflammation with infantile enterocolitis

An autosomal dominant disorder characterized by neonatal-onset enterocolitis, periodic fever, and fatal or near-fatal episodes of autoinflammation. Affected individuals tend to have poor overall growth and gastrointestinal symptoms in infancy, recurrent febrile episodes with splenomegaly, and sometimes hematologic disturbances, arthralgias, or myalgias.

Autoinflammation, panniculitis, and dermatosis syndrome, autosomal recessive

An autosomal recessive autoinflammatory disorder characterized by neonatal-onset of fever, neutrophilic dermatitis, panniculitis, painful joints, failure to thrive. Patients do not exhibit overt primary immunodeficiency.

Proteasome-associated autoinflammatory syndrome 4

An autosomal recessive, autoinflammatory disorder characterized by panniculitis and erythematous skin lesions apparent in early infancy. Additional features include hepatosplenomegaly, lymphadenopathy, autoimmune hemolytic anemia, fever, generalized lipodystrophy, myositis, joint contractures, and mild motor and speech delay.

Blau syndrome

An autosomal dominant inflammatory disorder characterized by the formation of immune granulomas invading the skin, joints and eye. Other organs may be involved. Clinical manifestations are variable and include early-onset granulomatous arthritis, uveitis and skin rash. Blindness, joint destruction and visceral involvement have been reported in severe cases.

Autoinflammatory syndrome, familial, Behcet-like 1

An autosomal dominant, autoinflammatory disorder with early onset, characterized by ulceration of mucosal surfaces, particularly in the oral and genital areas. Additional variable features include skin rash, uveitis, and polyarthritis.

Autoinflammatory disease, systemic, with vasculitis

An autosomal dominant disorder characterized by systemic autoinflammation manifesting in the first hours of life with diffuse purpuric skin lesions, fever, hepatosplenomegaly, and increased C-reactive protein. Additional clinical features include periorbital edema, conjunctivitis, urticaria, atopic dermatitis, abdominal pain, and arthralgia. Laboratory studies may show leukocytosis, thrombocytopenia, and autoantibodies.

Familial cold autoinflammatory syndrome 2

A rare autosomal dominant systemic inflammatory disease characterized by recurrent episodes of maculopapular rash associated with arthralgias, myalgias, fever and chills, swelling of the extremities, and conjunctivitis after generalized exposure to cold.

Cherubism

An autosomal dominant syndrome characterized by excessive bone degradation of the upper and lower jaws, which often begins around three years of age. It is followed by development of fibrous tissue masses, which causes a characteristic facial swelling.

Aicardi-Goutieres syndrome 4

A form of Aicardi-Goutieres syndrome, a genetically heterogeneous disease characterized by cerebral atrophy, leukoencephalopathy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infection. Clinical features as thrombocytopenia, hepatosplenomegaly and elevated hepatic transaminases along with intermittent fever may erroneously suggest an infective process. Severe neurological dysfunctions manifest in infancy as progressive microcephaly, spasticity, dystonic posturing and profound psychomotor retardation. Death often occurs in early childhood.

Proteasome-associated autoinflammatory syndrome 3

An autoinflammatory disorder characterized by onset in early infancy and recurrent fever, nodular dermatitis, myositis, panniculitis-induced lipodystrophy, lymphadenopathy, and immune dysregulation. Variable accompanying features may include joint contractures, hepatosplenomegaly, anemia, thrombocytopenia, recurrent infections, autoantibodies, and hypergammaglobulinemia. Some patients may have intracranial calcifications. PRAAS3 inheritance is autosomal recessive or digenic.

Aicardi-Goutieres syndrome 8

A form of Aicardi-Goutieres syndrome, a genetically heterogeneous disease characterized by cerebral atrophy, leukoencephalopathy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infection. Clinical features as thrombocytopenia, hepatosplenomegaly and elevated hepatic transaminases along with intermittent fever may erroneously suggest an infective process. Severe neurological dysfunctions manifest in infancy as progressive microcephaly, spasticity, dystonic posturing and profound psychomotor retardation. Death often occurs in early childhood. AGS8 inheritance is autosomal recessive.

Aicardi-Goutieres syndrome 1

A form of Aicardi-Goutieres syndrome, a genetically heterogeneous disease characterized by cerebral atrophy, leukoencephalopathy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infection. Clinical features as thrombocytopenia, hepatosplenomegaly and elevated hepatic transaminases along with intermittent fever may erroneously suggest an infective process. Severe neurological dysfunctions manifest in infancy as progressive microcephaly, spasticity, dystonic posturing and profound psychomotor retardation. Death often occurs in early childhood.

Pigmentary disorder, reticulate, with systemic manifestations, X-linked

An X-linked recessive disorder characterized by recurrent infections and sterile inflammation in various organs. Diffuse skin hyperpigmentation with a distinctive reticulate pattern is universally evident by early childhood. This is later followed in many patients by hypohidrosis, corneal inflammation and scarring, enterocolitis that resembles inflammatory bowel disease, and recurrent urethral strictures. Melanin and amyloid deposition is present in the dermis. Affected males also have a characteristic facies with frontally upswept hair and flared eyebrows. Female carriers have only restricted pigmentary changes along Blaschko's lines.

Trichohepatoenteric syndrome 1

A syndrome characterized by intrauterine growth retardation, severe diarrhea in infancy requiring total parenteral nutrition, facial dysmorphism, immunodeficiency, and hair abnormalities, mostly trichorrhexis nodosa. Hepatic involvement contributes to the poor prognosis of affected patients.

Spondyloenchondrodysplasia with immune dysregulation

A disease characterized by vertebral and metaphyseal dysplasia, spasticity with cerebral calcifications, and strong predisposition to autoimmune diseases. The skeletal dysplasia is characterized by radiolucent and irregular spondylar and metaphyseal lesions that represent islands of chondroid tissue within bone.

Trichohepatoenteric syndrome 2

A syndrome characterized by intrauterine growth retardation, severe diarrhea in infancy requiring total parenteral nutrition, facial dysmorphism, immunodeficiency, and hair abnormalities, mostly trichorrhexis nodosa. Hepatic involvement contributes to the poor prognosis of affected patients.

Pseudo-TORCH syndrome 2

An autosomal recessive multisystem disorder characterized by antenatal onset of intracranial hemorrhage, calcification, brain malformations, liver dysfunction, and often thrombocytopenia. Affected individuals tend to have respiratory insufficiency and seizures, and die in infancy. The phenotype resembles the sequelae of intrauterine infection, but there is no evidence of an infectious agent.

Proteasome-associated autoinflammatory syndrome 5

An autosomal recessive, autoinflammatory disorder characterized by recurrent, polymorphic disseminated cutaneous rash with annular lesions, non-specific lymphocytic infiltration in the skin, fever, failure to thrive, and persistent hepatosplenomegaly. Disease onset is in early infancy.

Spinal muscular atrophy X-linked 2

A lethal infantile form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. Clinical features include hypotonia, areflexia, and multiple congenital contractures.

Type 1 diabetes mellitus 19

A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.

STING-associated vasculopathy, infantile-onset

An autoinflammatory disease characterized by early-onset systemic inflammation and cutaneous vasculopathy, resulting in severe skin lesions. Violaceous, scaling lesions of fingers, toes, nose, cheeks and ears progress to acral necrosis in most of the patients. Some patients have severe interstitial lung disease.

Dyschromatosis symmetrica hereditaria

An autosomal dominant pigmentary genodermatosis characterized by a mixture of hyperpigmented and hypopigmented macules distributed on the face and the dorsal parts of the hands and feet, that appear in infancy or early childhood.

Microvascular complications of diabetes 4

Pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis.

Familial Mediterranean fever, autosomal recessive

A hereditary periodic fever syndrome characterized by recurrent episodic fever, serosal inflammation and pain in the abdomen, chest or joints. It is frequently complicated by reactive amyloidosis, which leads to renal failure and can be prophylactically treated with colchicine.

Pyogenic sterile arthritis, pyoderma gangrenosum, and acne

A rare autosomal dominant autoinflammatory disease that typically presents with recurrent sterile, erosive arthritis in childhood, occurring spontaneously or after minor trauma, occasionally resulting in significant joint destruction. By puberty, joint symptoms tend to subside and cutaneous symptoms increase. Cutaneous manifestations include pathergy, frequently with abscesses at the sites of injections, severe cystic acne, and recurrent nonhealing sterile ulcers, often diagnosed as pyoderma gangrenosum.

Proteasome-associated autoinflammatory syndrome 3

An autoinflammatory disorder characterized by onset in early infancy and recurrent fever, nodular dermatitis, myositis, panniculitis-induced lipodystrophy, lymphadenopathy, and immune dysregulation. Variable accompanying features may include joint contractures, hepatosplenomegaly, anemia, thrombocytopenia, recurrent infections, autoantibodies, and hypergammaglobulinemia. Some patients may have intracranial calcifications. PRAAS3 inheritance is autosomal recessive or digenic.

Familial cold autoinflammatory syndrome 1

A rare autosomal dominant systemic inflammatory disease characterized by recurrent episodes of maculopapular rash associated with arthralgias, myalgias, fever and chills, swelling of the extremities, and conjunctivitis after generalized exposure to cold. Rarely, some patients may also develop late-onset renal amyloidosis.

Periodic fever, familial, autosomal dominant

A hereditary periodic fever syndrome characterized by recurrent fever, abdominal pain, localized tender skin lesions and myalgia. Reactive amyloidosis is the main complication and occurs in 25% of cases.

Familial cold autoinflammatory syndrome 3

An autosomal dominant immune disorder characterized by the development of cutaneous urticaria, erythema, and pruritis in response to cold exposure. Affected individuals have variable additional immunologic defects, including antibody deficiency, decreased numbers of B-cells, defective B-cells, increased susceptibility to infection, and increased risk of autoimmune disorders.

Vasculitis, autoinflammation, immunodeficiency, and hematologic defects syndrome

An autosomal recessive, systemic necrotizing vasculitis that affects medium and small arteries. The ensuing tissue ischemia can affect any organ, including the skin, musculoskeletal system, kidneys, gastrointestinal tract, and the cardiovascular and nervous systems. Organ involvement and disease severity are highly variable. Clinical features include recurrent ischemic stroke affecting the small vessels of the brain and resulting in neurologic dysfunction, recurrent fever, myalgias, livedoid rash, gastrointestinal pain and hepatosplenomegaly.

Singleton-Merten syndrome 2

A form of Singleton-Merten syndrome, an autosomal dominant disorder characterized by marked aortic calcification, dental anomalies, osteopenia, acro-osteolysis, and to a lesser extent glaucoma, psoriasis, muscle weakness, and joint laxity. Additional clinical manifestations include particular facial characteristics and abnormal joint and muscle ligaments. SGMRT2 is an atypical form characterized by variable expression of glaucoma, aortic calcification, and skeletal abnormalities, without dental anomalies.

Psoriasis 14, pustular

A life-threatening disease defined by repeated flares of sudden onset consisting of diffuse erythematous skin eruption characterized by rapid coverage with pustules, high-grade fever, asthenia, marked leukocytosis, and elevated serum levels of C-reactive protein.

Keratosis linearis with ichthyosis congenita and sclerosing keratoderma

A keratinizing disorder characterized by ichthyosis, palmoplantar keratoderma with constricting bands around fingers, flexural deformities of fingers and keratotic papules in a linear distribution on the flexural side of large joints. Histological examination of the skin of affected individuals shows hypertrophy and hyperplasia of the spinous, granular and horny epidermal layer.

Proteasome-associated autoinflammatory syndrome 1

An autosomal recessive autoinflammatory disorder characterized by early childhood onset of recurrent fever, joint stiffness and severe contractures of the hands and feet, and erythematous skin lesions with subsequent development of lipodystrophy and laboratory evidence of immune dysregulation. Accompanying features may include muscle weakness and atrophy, hepatosplenomegaly, and microcytic anemia.

Lung cancer

A common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis.

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.