Hypotrichosis with juvenile macular dystrophy (HJMD) is an autosomal recessive disease with progressive macular degeneration leading to blindness in the first three decades of life along with hypotrichosis. We herein report a case of a five year old boy with hypotrichosis with juvenile macular dystrophy diagnosed with multi-modal imaging which was later confirmed by genetic testing by whole genome sequencing. Fundus examination of both eyes revealed symmetrical hypopigmentation in peripapillary retinal pigment epithelium (RPE) involving posterior pole and surrounded by a mottled hyperpigmented border. Fundus autofluorescence showed central hypo autofluorescence with surrounding hyper autofluorescence corresponding to RPE atrophy and a faint hypo autofluorescence at the junction of normal retina. SD-OCT showed segmental outer retinal and choriocapillaris atrophy temporal to fovea with interdigitation zone and ellipsoid zone loss and RPE irregularities with hyperreflective subretinal deposits at the fovea. Electroretinogram showed normal waves but a slight reduction of b wave amplitude in both eyes. He had sparse scalp-hair. Children with reduced vision not falling into a typical macular degeneration should be examined systemically and may just have sparse scalp hair and still have a genetic disease. A regular follow-up should be emphasized in view of progressive nature of the disease.

Cadherins are a superfamily of calcium-dependent intercellular adhesion molecules that are widely expressed in living tissues. Within the retina and retinal pigment epithelium (RPE), cadherins contribute to tissue morphogenesis, neural circuit formation, adherens junctions of the outer blood-retinal barrier, photoreceptor disc morphogenesis, maintenance and survival. Four monogenic disorders involving genes which encode cadherins have been identified as causes of inherited retinal degeneration: the retinal cadherinopathies (CDHR1, CDH23, PCDH15, CDH3). Biallelic variants in CDHR1 result in cone-rod dystrophy, rod-cone dystrophy or late-onset macular dystrophy which may be misclassified as dry age-related macular degeneration. Biallelic variants in CDH23 and PCDH15 underlie Usher Syndrome type 1D and 1F. Hypotrichosis with juvenile macular dystrophy results from biallelic variants in CDH3, which contributes to adherens tight junctions between RPE cells. In this review, we summarise the classification of cadherins, and the role of cadherins in the physiology and morphogenesis of the inner and outer retina. Cadherins expressed in primate photoreceptors (CDHR1, CDH23 and PCDH15) have evolved complex roles in outer segment disc morphogenesis and maintenance involving intracellular heterophilic interactions which are as yet incompletely characterised. We highlight what is currently unknown about the molecular function of these cadherins, and review the pathogenesis, clinical phenotype and molecular genetics of each monogenic retinal cadherinopathy. Genes regulating the expression and post-translational modification of retinal cadherins, or those coding for as yet unidentified interacting partners, are candidates for unsolved cases of retinal degeneration. This group of disorders is potentially treatable; we summarise the likely molecular therapeutic approaches and future directions for each retinal cadherinopathy.

Pathogenic variants in the Cadherin 3 (CDH3) gene are responsible for the occurrence of Hypotrichosis with Juvenile Macular Dystrophy (HJMD) and Ectodermal Dysplasia, Ectrodactyly and Macular Dystrophy Syndrome (EEMS), both of which are rare autosomal recessive disorders characterized by hypotrichosis and progressive macular dystrophy. The CDH3 gene encodes for P-cadherin, a calcium-binding protein that is essential for cell-cell adhesion, which is expressed in the retinal pigment epithelial cells and hair follicles. Fundus examination of both eyes was done in addition to clinical investigation. Genomic DNA was extracted from a whole-blood sample and whole-exome sequencing (WES) was performed to identify the underlying etiology.All identified variants were evaluated for their pathogenicity and causality. We present the first case of HJMD in a 23-year-old female patient from Jordan. The patient presented to our ophthalmology clinic with poor vision in both eyes. Gross examination revealed sparse scalp hair along with macular dystrophy on fundus exam in both eyes. HJMD was suspected and whole-exome sequencing (WES) confirmed the diagnosis with the identification of a homozygous frameshift deletion (p.Gly277AlafsTer20) localised in exon 7 of the CDH3 gene. Blindness due to progressive macular degeneration is a common manifestation in numerous syndromic recessive disorders such as HJMD. Ophthalmologists should consider the importance of systemic manifestations and genetic testing for the confirmation of diagnosis.