MedGen

Neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures (NEDLBAS), is characterized by global developmental delay with variably impaired intellectual development apparent from infancy or early childhood. Affected individuals have significant speech delay, and most demonstrate behavioral abnormalities, including autistic features. About half of patients develop seizures, which may be controlled or refractory. More variable features include hypotonia, feeding difficulties, and subtle facial dysmorphism (Schalk et al., 2022). [from OMIM]

Birk-Aharoni syndrome (BKAH) is a severe neurodevelopmental disorder characterized developmental delay, impaired intellectual development, absent speech, spastic tetraplegia with central hypotonia, chorea, inability to walk, hearing loss, micropenis, undescended testes, and mildly elevated liver enzymes (Aharoni et al., 2022). [from OMIM]

Neurodevelopmental disorder with microcephaly, hypotonia, and absent language (NEDMHAL) is a severe autosomal recessive disorder characterized by the constellation of these features. Behavioral problems and hearing loss are also present (Ansar et al., 2020). [from OMIM]

Neurocardiofaciodigital syndrome (NCFD) is characterized by severe developmental delay, variable brain anomalies, congenital heart defects, dysmorphic facial features, and a distinctive type of synpolydactyly with a supernumerary hypoplastic digit between the fourth and fifth digits of the hands and/or feet. Other features include eye abnormalities, hearing impairment, and electroencephalogram anomalies (summary by Horn et al., 2021). [from OMIM]

Global developmental delay with speech and behavioral abnormalities (GDSBA) is characterized by developmental delay apparent from infancy or early childhood. Affected individuals have mildly delayed fine and motor skills with walking by 3 years of age, mildly impaired intellectual development, speech and language delay, and variable behavioral abnormalities, mostly autism and ADHD. Some patients may have additional nonspecific features, such as facial dysmorphism, myopia or strabismus, and skeletal defects, including joint hypermobility, pes planus, or slender fingers (summary by Granadillo et al., 2020). [from OMIM]

Deafness, cataract, impaired intellectual development, and polyneuropathy (DCIDP) is characterized by early-onset of deafness, cataract, severe developmental delay, and severely impaired intellectual development. Patients later develop polyneuropathy of the lower extremities, associated with depigmentation of the hair in that area (Kroll-Hermi et al., 2020). [from OMIM]

Cardioacrofacial dysplasia-1 (CAFD1) is characterized by congenital cardiac defects, primarily common atrium or atrioventricular septal defect; limb anomalies, including short limbs, brachydactyly, and postaxial polydactyly; and dysmorphic facial features (Palencia-Campos et al., 2020). Genetic Heterogeneity of Cardioacrofacial Dysplasia CAFD2 (619143) is caused by mutation in the PRKACB gene (176892) on chromosome 1p31. [from OMIM]

Lessel-Kreienkamp syndrome (LESKRES) is a neurodevelopmental disorder characterized by global developmental delay with intellectual disability and speech and language delay apparent from infancy or early childhood. The severity of the disorder is highly variable: some patients have mildly delayed walking and mild cognitive deficits, whereas others are nonambulatory and nonverbal. Most have behavioral disorders. Additional features, including seizures, hypotonia, gait abnormalities, visual defects, cardiac defects, and nonspecific dysmorphic facial features, may also be present (summary by Lessel et al., 2020). [from OMIM]

Cardioacrofacial dysplasia-2 (CAFD2) is characterized by congenital cardiac defects, primarily common atrium or atrioventricular septal defect; limb anomalies, including short limbs, brachydactyly, and postaxial polydactyly; and dysmorphic facial features. Developmental delay of variable severity has also been observed (Palencia-Campos et al., 2020). For a discussion of genetic heterogeneity of CAFD, see CAFD1 (619142). [from OMIM]

Proteasome-associated autoinflammatory syndrome-3 is an autosomal recessive syndrome with onset in early infancy. Affected individuals present with nodular dermatitis, recurrent fever, myositis, panniculitis-induced lipodystrophy, lymphadenopathy, and dysregulation of the immune response, particularly associated with abnormal type I interferon-induced gene expression patterns. Additional features are highly variable, but may include joint contractures, hepatosplenomegaly, anemia, thrombocytopenia, recurrent infections, autoantibodies, and hypergammaglobulinemia. Some patients may have intracranial calcifications (summary by Brehm et al., 2015). For a discussion of genetic heterogeneity of PRAAS, see PRAAS1 (256040). [from OMIM]

IDDMSSD is a neurodevelopmental disorder characterized by impaired intellectual development, poor speech, postnatal macrocephaly, and seizures (Harms et al., 2018). [from OMIM]

This autosomal recessive systemic autoinflammatory disorder is characterized by early childhood onset of annular erythematous plaques on the face and extremities with subsequent development of partial lipodystrophy and laboratory evidence of immune dysregulation. More variable features include recurrent fever, severe joint contractures, muscle weakness and atrophy, hepatosplenomegaly, basal ganglia calcifications, and microcytic anemia (summary by Agarwal et al., 2010; Kitamura et al., 2011; Arima et al., 2011). This disorder encompasses Nakajo-Nishimura syndrome (NKJO); joint contractures, muscular atrophy, microcytic anemia, and panniculitis-induced lipodystrophy (JMP syndrome); and chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome (CANDLE). Among Japanese patients, this disorder is best described as Nakajo-Nishimura syndrome, since both Nakajo (1939) and Nishimura et al. (1950) contributed to the original phenotypic descriptions. Genetic Heterogeneity of Proteasome-Associated Autoinflammatory Syndrome See also PRAAS2 (618048), caused by mutation in the POMP gene (613386) on chromosome 13q12; PRAAS3 (617591), caused by mutation in the PSMB4 gene (602177) on chromosome 1q21; PRAAS4 (619183), caused by mutation in the PSMG2 gene (609702) on chromosome 18p11; and PRAAS5 (619175), caused by mutation in the PSMB10 gene (176847) on chromosome 16q22. [from OMIM]

A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by global developmental delay and moderate to severe intellectual disability, as well as variable other manifestations, such as macro- or microcephaly, epilepsy, hypotonia, behavioral problems, stereotypic movements, and facial dysmorphism (including arched eyebrows, long palpebral fissures, prominent nasal bridge, upturned nose, dysplastic ears, and broad mouth), among others. Brain imaging may show cerebellar anomalies, hypoplastic corpus callosum, enlarged ventricles, polymicrogyria, or white matter abnormalities. [from ORDO]

Stankiewicz-Isidor syndrome (STISS) is a neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, behavioral disorders, mild craniofacial anomalies, and variable congenital defects of the cardiac and/or urogenital systems (summary by Kury et al., 2017). [from OMIM]

Takenouchi-Kosaki syndrome is a highly heterogeneous autosomal dominant complex congenital developmental disorder affecting multiple organ systems. The core phenotype includes delayed psychomotor development with variable intellectual disability, dysmorphic facial features, and cardiac, genitourinary, and hematologic or lymphatic defects, including thrombocytopenia and lymphedema. Additional features may include abnormalities on brain imaging, skeletal anomalies, and recurrent infections. Some patients have a milder disease course reminiscent of Noonan syndrome (see, e.g., NS1, 163950) (summary by Martinelli et al., 2018). [from OMIM]

A rare isolated hereditary giant platelet disorder characterized by severe thrombocytopenia and thrombopathy due to defects in proplatelet formation and platelet activation in homozygous patients. Clinical manifestation are recurrent bleeding episodes including epistaxis, spontaneous hematomas, and menorrhagia. [from ORDO]

Cushing syndrome is a clinical designation for the systemic signs and symptoms arising from excess cortisol production. Affected individuals typically show hypertension, impaired glucose tolerance, central obesity, osteoporosis, and sometimes depression. Corticotropin-independent Cushing syndrome results from autonomous cortisol production by the adrenal glands, often associated with adrenocortical tumors. Adrenocortical tumors are most common in adult females (summary by Cao et al., 2014; Sato et al., 2014). [from OMIM]

A rare, genetic, non-severe combined immunodeficiency disease characterized by immunodeficiency (manifested by recurrent and/or severe bacterial and viral infections), destructive noninfectious granulomas involving skin, mucosa and internal organs, and various autoimmune manifestations (including cytopenias, vitiligo, psoriasis, myasthenia gravis, enteropathy). Immunophenotypically, T-cell and B-cell lymphopenia, hypogammaglobulinemia, abnormal specific antibody production and impaired T-cell function are observed. [from ORDO]