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Prevalence is unknown but approximately 50 patients have been described since the first characterization of the syndrome in 1935.

HJMD patients present with short and sparse scalp hair since birth or first months of life, with no subsequent growth during life. A decade later, during the first to third decades of life, visual acuity decreases because of progressive macular degeneration, leading in many cases to blindness between the second and fourth decades of life. HJMD is sometimes associated with limb anomalies, in which case it is termed Ectodermal dysplasia, Ectrodactyly, and Macular dystrophy (EEM; see this term). Many patients display fair hair complexion as compared with their healthy siblings. The hair phenotype does not improve significantly with age, even though diffuse alopecia in infancy can evolve towards short and sparse hair in puberty.

HJMD is caused by mutations in the CDH3 gene (16q22.1), encoding P-cadherin. P-cadherin is part of adherens junctions in various epithelia including the hair follicular epithelium. Moreover, P-cadherin is expressed in the retinal pigment epithelium.

Diagnosis is based on the combined occurrence of hypotrichosis with characteristic degenerative changes and pigmentary abnormalities of the macula on fundoscopy. Where available, electrophysiologic studies can confirm abnormal function of the posterior pole. Additional tests of lesser diagnostic value include (1) histopathologic examination of scalp biopsies, revealing mostly vellus and catagen hair follicles with significantly reduced number of terminal hair follicles; (2) light microscopy and scanning electron microscopy of hair which can demonstrate various structural abnormalities including pseudomonilethrix, pili torti, longitudinal ridging, scaling and folding of the hair shaft.

Differential diagnosis includes EEM syndrome, also caused by CDH3 mutations.

DNA-based prenatal diagnosis and genetic counseling are available provided the underlying mutation is known.

As HJMD is an autosomal recessive disease, risk of recurrence is 25%.

No curative or palliative options exist for HJMD. However, educational measures can be implemented and psychological support should be provided once HJMD is diagnosed.

The most severe complication of HJMD is progressive macular degeneration leading to blindness between the second and fourth decades of life. Life expectancy is normal but quality of life can be reduced because of blindness and psychological impact due to the hair phenotype.