MedGen

Chediak-Higashi syndrome (CHS) is characterized by partial oculocutaneous albinism, immunodeficiency, and a mild bleeding tendency. Approximately 85% of affected individuals develop the accelerated phase, or hemophagocytic lymphohistiocytosis, a life-threatening, hyperinflammatory condition. All affected individuals including adolescents and adults with atypical CHS and children with classic CHS who have successfully undergone allogenic hematopoietic stem cell transplantation (HSCT) develop neurologic findings during early adulthood. [from GeneReviews]

Hermansky-Pudlak syndrome (HPS) is characterized by oculocutaneous albinism, a bleeding diathesis, and, in some individuals, pulmonary fibrosis, granulomatous colitis, or immunodeficiency. Ocular findings include reduced iris pigment with iris transillumination, reduced retinal pigment, foveal hypoplasia with significant reduction in visual acuity (usually in the range of 20/50 to 20/400), nystagmus, and increased crossing of the optic nerve fibers. Hair color ranges from white to brown; skin color ranges from white to olive and is usually a shade lighter than that of other family members. The bleeding diathesis can result in variable bruising, epistaxis, gingival bleeding, postpartum hemorrhage, colonic bleeding, and prolonged bleeding with menses or after tooth extraction, circumcision, and other surgeries. Pulmonary fibrosis, a restrictive lung disease, typically causes symptoms in the early thirties and can progress to death within a decade. Granulomatous colitis is severe in about 15% of affected individuals. Neutropenia and/or immune defects occur primarily in individuals with pathogenic variants in AP3B1 and AP3D1. [from GeneReviews]

Oculocutaneous albinism type 4 (OCA4) is characterized by hypopigmentation of the hair and skin plus the characteristic ocular changes found in all other types of albinism, including: nystagmus; reduced iris pigment with iris translucency; reduced retinal pigment with visualization of the choroidal blood vessels on ophthalmoscopic examination; foveal hypoplasia associated with reduction in visual acuity; and misrouting of the optic nerves at the chiasm associated with alternating strabismus, reduced stereoscopic vision, and an altered visual evoked potential (VEP). Individuals with OCA4 are usually recognized within the first year of life because of hypopigmentation of the hair and skin and the ocular features of nystagmus and strabismus. Vision is likely to be stable after early childhood. The amount of cutaneous pigmentation in OCA4 ranges from minimal to near normal. Newborns with OCA4 usually have some pigment in their hair, with color ranging from silvery white to light yellow. Hair color may darken with time, but does not vary significantly from childhood to adulthood. [from GeneReviews]

With the current widespread use of multigene panels and comprehensive genomic testing, it has become apparent that the phenotypic spectrum of EPG5-related disorder represents a continuum. At the most severe end of the spectrum is classic Vici syndrome (defined as a neurodevelopmental disorder with multisystem involvement characterized by the combination of agenesis of the corpus callosum, cataracts, hypopigmentation, cardiomyopathy, combined immunodeficiency, microcephaly, and failure to thrive); at the milder end of the spectrum are attenuated neurodevelopmental phenotypes with variable multisystem involvement. Median survival in classic Vici syndrome appears to be 24 months, with only 10% of children surviving longer than age five years; the most common causes of death are respiratory infections as a result of primary immunodeficiency and/or cardiac insufficiency resulting from progressive cardiac failure. No data are available on life span in individuals at the milder end of the spectrum. [from GeneReviews]

Pierson syndrome (PIERS) is an autosomal recessive disorder comprising congenital nephrotic syndrome with diffuse mesangial sclerosis and distinct ocular abnormalities, including microcoria and hypoplasia of the ciliary and pupillary muscles, as well as other anomalies. Many patients die early, and those who survive tend to show neurodevelopmental delay and visual loss (summary by Zenker et al., 2004). Mutations in the LAMB2 gene also cause nephrotic syndrome type 5 with or without mild ocular anomalies (NPHS5; 614199). [from OMIM]

Jacobsen syndrome (JBS) is a contiguous gene deletion syndrome with major clinical features of growth retardation, psychomotor retardation, trigonocephaly, divergent intermittent strabismus, epicanthus, telecanthus, broad nasal bridge, short nose with anteverted nostrils, carp-shaped upper lip, retrognathia, low-set dysmorphic ears, bilateral camptodactyly, hammertoes, and isoimmune thrombocytopenia (Fryns et al., 1986, Epstein, 1986). [from OMIM]

Characteristic features of the distal 3p- syndrome include low birth weight, microcephaly, trigonocephaly, hypotonia, psychomotor and growth retardation, ptosis, telecanthus, downslanting palpebral fissures, and micrognathia. Postaxial polydactyly, renal anomalies, cleft palate, congenital heart defects (especially atrioventricular septal defects), preauricular pits, sacral dimple, and gastrointestinal anomalies are variable features. Although intellectual deficits are almost invariably associated with cytogenetically visible 3p deletions, rare patients with a 3p26-p25 deletion and normal intelligence or only mild abnormalities have been described (summary by Shuib et al., 2009). [from OMIM]

Knobloch syndrome-1 (KNO1) is an autosomal recessive developmental disorder primarily characterized by typical eye abnormalities, including high myopia, cataracts, dislocated lens, vitreoretinal degeneration, and retinal detachment, with occipital skull defects, which can range from occipital encephalocele to occult cutis aplasia (summary by Aldahmesh et al., 2011). Genetic Heterogeneity of Knobloch Syndrome KNO2 (618458) is caused by mutation in the PAK2 gene (605022) on chromosome 3q29. [from OMIM]

Congenital hydrocephalus-2 (HYC2) is a congenital disorder with onset in utero. Affected individuals have hydrocephalus with variably dilated ventricles and variable neurologic sequelae. Some individuals have other brain abnormalities, including lissencephaly, thinning of the corpus callosum, and neuronal heterotopia. Most patients have delayed motor development and some have delayed intellectual development and/or seizures. Additional congenital features, including cardiac septal defects, iris coloboma, and nonspecific dysmorphic features, may be observed. Some patients die in utero, in infancy, or in early childhood, whereas others have long-term survival (summary by Shaheen et al., 2017). For a discussion of genetic heterogeneity of congenital hydrocephalus, see 233600. [from OMIM]

Male EBP disorder with neurologic defects (MEND) is an X-linked recessive disorder representing a continuous phenotypic spectrum with variable manifestations associated with a defect in sterol biosynthesis. Features include intellectual disability, short stature, scoliosis, digital abnormalities, cataracts, and dermatologic abnormalities. Not all patients show all features, and the severity is highly variable. Molecular studies indicate that affected males are hemizygous for a nonmosaic hypomorphic EBP allele. Carrier females are generally clinically asymptomatic, but may show biochemical abnormalities (summary by Arnold et al., 2012 and Barboza-Cerda et al., 2014). [from OMIM]

Mutations in the MAF gene have been found to cause multiple types of cataract, which have been described as cortical pulverulent, lamellar, nuclear, nuclear pulverulent, nuclear stellate, anterior polar, anterior subcapsular, posterior subcapsular, and cerulean. In some cases, the cataracts are of juvenile onset. The preferred title of this entry was formerly 'Cataract, Pulverulent, Juvenile-Onset,' with an 'Included' title/symbol of 'Cataract, Congenital, Cerulean Type, 4; CCA4.' [from OMIM]

Oculoauricular syndrome (OCACS) is characterized by complex ocular anomalies, including congenital cataract, anterior segment dysgenesis, iris coloboma, and early-onset retinal dystrophy, and dysplastic ears with abnormal external ear cartilage (summary by Gillespie et al., 2015). [from OMIM]

Underdevelopment of the macula lutea. [from HPO]