Congenital Hypotrichosis with Juvenile Macular Dystrophy


Disease group Ectodermal Dysplasia
Synonymous HJMD, Hypotrichosis with cone-rod dystrophy
Estimated prevalence -
OMIM 601553
Inheritance Autosomal Recessive
Gene (s) CDH3 (114021)


Congenital hypotrichosis with juvenile macular dystrophy (HJMD) is a rare autosomal recessive syndrome first reported by Wagner in 1935. Characteristic features comprise hair loss and progressive macular degeneration leading to reduced visual acuity and early blindness.1

Clinical Description

Few cases of HJMD have been described in the literature. Patients present in childhood or adolescence with central visual disturbance, sparse scalp hair and a predominantly macular dystrophy. Reduced visual acuity is common, frequently deteriorating over time.2 Sprecher at al. described several affected Israeli families who were born with normal hair, developed scalp alopecia at an age of 3 months and subsequently had spontaneous regrowth of short, sparse hair during puberty. Pili torti and fusiform beading along the hair shaft was seen on examination by light and scanning electron microscopy. Affected individuals developed progressive macular degeneration and fundus examination revealed pigmentary abnormalities with atrophic changes at the posterior pole extending beyond the macular region.3 Leibu at al. performed a fundus examination on 16 affected individuals which also revealed retinal abnormalities extending beyond the macula to more peripheral areas.4


The defective gene in HJMD is CDH3, encoding P-cadherin, which is expressed in the retinal pigment epithelium and hair follicles. It forms a major component of adherens junctions important in cell-cell interactions and for formation of e.g. desmosomes.5,6


Diagnosis is made by assessment of the clinical features of hair loss and reduced visual acuity in childhood. Genomic DNA should be analysed for a CDH3 gene mutation in order to confirm the diagnosis and assist with genetic counselling. No genotype-phenotype correlation has been established so far.


EEMS (ectodermal dysplasia, ectrodactyly and macular dystrophy syndrome) [OMIM 225280] is a similar condition (EEM and HJMD are allelic disorders) and is associated with hypotrichosis and macular dystrophy with the additional features of ectodermal dysplasia (e.g. hypotrichosis, nail dysplasia, partial anodontia) and limb defects (e.g. ectrodactyly - missing phalanges, syndactyly - joined digits, campylodactyly - bent digits). EEMS is caused by biallelic CDH3 mutations.7


Here is no effective treatment for congenital hypotrichosis. Cosmetic camouflage with wigs may be an option for patients.

Affected individuals with HJMD require regular assessment by an ophthalmologist for evaluation and management of macular degeneration.




1. Wagner  H.  Maculaaffektion, vergesellschaftet mit Haarabnormität von Lanugotypus, beide vielleicht angeboren bei zwei Geschwistern.  Albrecht Von Graefes Arch Ophthalmol. 1935;134:74-81.

2. Hull S, Arno G, Robson AG, et al. Characterization of CDH3-Related Congenital Hypotrichosis With Juvenile Macular Dystrophy. JAMA Ophthalmol. 2016;134(9):992–1000.

3. Sprecher  E, Bergman  R, Richard  G,  et al.  Hypotrichosis with juvenile macular dystrophy is caused by a mutation in CDH3, encoding P-cadherin.  Nat Genet. 2001;29(2):134-136.

4. Leibu  R, Jermans  A, Hatim  G, Miller  B, Sprecher  E, Perlman  I.  Hypotrichosis with juvenile macular dystrophy: clinical and electrophysiological assessment of visual function.  Ophthalmology. 2006;113(5):841-847.e3.

5. Indelman  M, Bergman  R, Lurie  R,  et al.  A missense mutation in CDH3, encoding P-cadherin, causes hypotrichosis with juvenile macular dystrophy.  J Invest Dermatol. 2002;119(5):1210-1213.

6. Huen  AC, Park  JK, Godsel  LM,  et al.  Intermediate filament-membrane attachments function synergistically with actin-dependent contacts to regulate intercellular adhesive strength.  J Cell Biol. 2002;159(6):1005-1017.

7. Basel-Vanagaite  L, Pasmanik-Chor  M, Lurie  R, Yeheskel  A, Kjaer  KW.  CDH3-related syndromes: report on a new mutation and overview of the genotype-phenotype correlations.  Mol Syndromol. 2010;1(5):223-230.