Hypotrichosis congenita with juvenile macular degenerationH35.9; L65.9

Wagner, 1935

Rare disease characterized by hypotrichosis with growth inhibition of the main hair (note: patients never have to go to the hairdresser) and progressive macular degeneration until complete blindness.

Autosomal recessive syndrome with missen mutations in the cadherin 3 gene (CDH3 gene), which codes for the P-cadherin protein (see cadherins below).

Clinically noticeable already in early infancy.

Hypotrichosis with smooth or curly, short, often blonde (disturbance of pigmentation?) hair and lentiginosis centrofacialis (occurs frequently). Due to the lack of hair growth, a visit to the hairdresser is not necessary. Occurrence of hair abnormalities ( Pili torti, Pseudomonilethrix, longitudinal cracks).

Irregular epithelium of the hair root sheath with apoptotic cells in the outer layer, thickened cuticle and fibrosing strands of the dermis. Increased ratio of vellus/terminal hairs possible.

The clinical picture in the described constellation of symptoms is diagnostically conclusive.

Increasing loss of visual acuity up to blindness.

The mechanism of the disease is still unclear: P-cadherin is expressed simultaneously with E-cadherin in the retina and in skin and follicular epithelia. E-cadherin is able to compensate a lack of P-cadherin during keratinocyte differentiation in vivo, a resulting lack of E-cadherin in the major part of the hair matrix might possibly explain the limitation of the changes to the hair follicle. P-cadherin appears to interact with many other cytoplasmic proteins and to play an important role during hair morphogenesis.