MedGen

Fanconi anemia (FA) is characterized by physical abnormalities, bone marrow failure, and increased risk for malignancy. Physical abnormalities, present in approximately 75% of affected individuals, include one or more of the following: short stature, abnormal skin pigmentation, skeletal malformations of the upper and/or lower limbs, microcephaly, and ophthalmic and genitourinary tract anomalies. Progressive bone marrow failure with pancytopenia typically presents in the first decade, often initially with thrombocytopenia or leukopenia. The incidence of acute myeloid leukemia is 13% by age 50 years. Solid tumors – particularly of the head and neck, skin, and genitourinary tract – are more common in individuals with FA. [from GeneReviews]

Xeroderma pigmentosum (XP) is characterized by: Acute sun sensitivity (severe sunburn with blistering, persistent erythema on minimal sun exposure) with marked freckle-like pigmentation of the face before age two years; Sunlight-induced ocular involvement (photophobia, severe keratitis, atrophy of the skin of the lids, ocular surface neoplasms); Greatly increased risk of sunlight-induced cutaneous neoplasms (basal cell carcinoma, squamous cell carcinoma, melanoma) within the first decade of life. Approximately 25% of affected individuals have neurologic manifestations (acquired microcephaly, diminished or absent deep tendon stretch reflexes, progressive sensorineural hearing loss, progressive cognitive impairment, and ataxia). The most common causes of death are skin cancer, neurologic degeneration, and internal cancer. The median age at death in persons with XP with neurodegeneration (29 years) was found to be younger than that in persons with XP without neurodegeneration (37 years). [from GeneReviews]

Vascular Ehlers-Danlos syndrome (vEDS) is characterized by arterial, intestinal, and/or uterine fragility; thin, translucent skin; easy bruising; characteristic facial appearance (thin vermilion of the lips, micrognathia, narrow nose, prominent eyes); and an aged appearance to the extremities, particularly the hands. Vascular dissection or rupture, gastrointestinal perforation, or organ rupture are the presenting signs in most adults with vEDS. Arterial rupture may be preceded by aneurysm, arteriovenous fistulae, or dissection but also may occur spontaneously. The majority (60%) of individuals with vEDS who are diagnosed before age 18 years are identified because of a positive family history. Neonates may present with clubfoot, hip dislocation, limb deficiency, and/or amniotic bands. Approximately half of children tested for vEDS in the absence of a positive family history present with a major complication at an average age of 11 years. Four minor diagnostic features – distal joint hypermobility, easy bruising, thin skin, and clubfeet – are most often present in those children ascertained without a major complication. [from GeneReviews]

Quigley (1993) reviewed adult-onset primary open angle glaucoma, which combines a particular abnormal appearance of the optic disc (optic nerve head) with a slowly progressive loss of visual sensitivity. Many patients with glaucoma have intraocular pressures above the normal range, although this cannot be considered part of the definition of the disease, since some patients have normal intraocular pressures. Changes in the optic disc, either inherited or acquired, contribute to the development of the disorder, which leads to visual loss from increasing nerve fiber layer atrophy. Quigley et al. (1994) stated that POAG should be reviewed as a multifactorial disorder. Genetic Heterogeneity of Primary Open Angle Glaucoma Other forms of primary open angle glaucoma include GLC1A (137750), caused by mutation in the MYOC gene (601652) on chromosome 1q24; GLC1B (606689) on chromosome 2cen-q13; GLC1C (601682) on chromosome 3q21-q24; GLC1D (602429) on chromosome 8q23; GLC1F (603383), caused by mutation in the ASB10 gene (615054) on chromosome 7q36; GLC1G (609887), caused by mutation in the WDR36 gene (609669) on chromosome 5q22; GLC1H (611276), caused by mutation in the EFEMP1 gene (601548) on chromosome 2p16; GLC1I (609745) on chromosome 15q11-q13; GLC1J (608695) on chromosome 9q22; GLC1K (608696) on chromosome 20p12; GLC1L (see 137750) on chromosome 3p22-p21; GLC1M (610535) on chromosome 5q22; GLC1N (611274) on chromosome 15q22-q24; GLC1O (613100), caused by mutation in the NTF4 gene (162662) on chromosome 19q13; GLC1P (177700), caused by an approximately 300-kb duplication on chromosome 12q24, most likely involving the TBK1 gene (604834). Nail-patella syndrome (NPS; 161200), which is caused by mutation in the LMX1B gene (602575) on chromosome 9q34, has open angle glaucoma as a pleiotropic feature. Other Forms of Glaucoma For a general description and a discussion of genetic heterogeneity of congenital forms of glaucoma, see GLC3A (231300). See 606657 for a discussion of normal tension glaucoma (NTG) or normal pressure glaucoma (NPG), a subtype of POAG. See 618880 for a discussion of primary closed-angle glaucoma. [from OMIM]