Phenotypic observations in "hypotrichosis with juvenile macular dystrophy" (recessive CDH3 mutations)

Recessive mutations in CDH3 cause "hypotrichosis with juvenile macular dystrophy," typically recognized by the presence of prominent dermatological features. We report novel phenotypic observations and associated mutations in four patients from three families, including one who did not have frank hypotrichosis.

Retrospective case series (2010-2014).

Four affected individuals from three consanguineous Arabian families were identified. All four subjects (two sisters and two unrelated males; 5, 13, 17, and 26 years old) had homozygous recessive CDH3 mutations not previously associated with the condition (c.307C>T; p.R103 in two sisters, c.1859_1862delCTCT in both unrelated males). Symptomatic visual loss was since birth or early childhood. One male subject did not have frank hypotrichosis, but review of symptoms revealed relatively slow hair growth and an inability to conceive children. None had dental or digital findings, although one female noted slow nail growth. All had a circumscribed central maculopathy with borders that did not respect posterior pole horizontal arterioles (typically extending beyond the major arcades) and associated with polygonal pigment clumping. Recognition of this pattern led us to suspect the diagnosis in the male without frank hypotrichosis. Retinal dysfunction was cone-rod (rather than macular only) by ERG in one patient, who developed severe central macular atrophy and a macular hole.

Ophthalmologists should consider the diagnosis of CDH3-related retinopathy in individuals with such clinical features whether or not there is frank hypotrichosis.