EEM Syndrome Clinical CharacteristicsOcular Features: Granular pigmentation and a grayish coloration of the retina may be present. The peripheral retina usually appears normal but the posterior pole and macula have pigmentary changes consisting of clumping and geographic atrophy. Fluorescein angiography shows patchy areas of hyperfluorescence. Patients in their 30s have been reported to have normal ERGs in one study. Reduced acuity can be noted in the first decade but progression is slow. Acuity levels in the 20/200 range may be seen in the fourth decade of life. Systemic Features: Ectodermal dysplasia with ectrodactyly and syndactyly are prominent features of this syndrome. Hypotrichosis of the scalp, eyebrows and eyelashes is often seen. Partial anodontia and diastema are also features. Syndactyly of the toes is present more frequently than found among the fingers. GeneticsThis is an autosomal recessive disorder resulting from mutations in the CDH3 gene (16q22.1). EEM syndrome is allelic to the Hypotrichosis with Macular Dystrophy syndrome (601553). However, the latter lacks the dental, limb, and digital anomalies as well as the hypotrichosis of eyebrows and eyelashes. Pedigree: Autosomal recessiveTreatmentTreatment Options: No treatment is available for this disease. ReferencesArticle Title: Distinct CDH3 mutations cause ectodermal dysplasia, ectrodactyly, macular dystrophy (EEM syndrome) Kjaer KW, Hansen L, Schwabe GC, Marques-de-Faria AP, Eiberg H, Mundlos S, Tommerup N, Rosenberg T. Distinct CDH3 mutations cause ectodermal dysplasia, ectrodactyly, macular dystrophy (EEM syndrome). J Med Genet. 2005 Apr;42(4):292-8. PubMed ID: 15805154 EEM syndrome: report of a family and results of a ten-year follow-up Balarin Silva V, Sim?ues AM, Marques-de-Faria AP. EEM syndrome: report of a family and results of a ten-year follow-up. Ophthalmic Genet. 1999 Jun;20(2):95-9. PubMed ID: 10420194 Read more about EEM Syndrome
Distinct CDH3 mutations cause ectodermal dysplasia, ectrodactyly, macular dystrophy (EEM syndrome) Kjaer KW, Hansen L, Schwabe GC, Marques-de-Faria AP, Eiberg H, Mundlos S, Tommerup N, Rosenberg T. Distinct CDH3 mutations cause ectodermal dysplasia, ectrodactyly, macular dystrophy (EEM syndrome). J Med Genet. 2005 Apr;42(4):292-8. PubMed ID: 15805154
EEM syndrome: report of a family and results of a ten-year follow-up Balarin Silva V, Sim?ues AM, Marques-de-Faria AP. EEM syndrome: report of a family and results of a ten-year follow-up. Ophthalmic Genet. 1999 Jun;20(2):95-9. PubMed ID: 10420194
Hypotrichosis with Juvenile Macular Degeneration Clinical CharacteristicsOcular Features: Macular dystrophy usually becomes symptomatic before the second decade of life but retinal evidence of macular degeneration can be seen in the first decade. EOG is usually normal while the ERG responses are decreased early and with time decrease further in amplitude. Pattern reversal VEPs are significantly subnormal even while vision is relatively good. Visual acuity decreases slowly in spite of significant deterioration of cone- and rod-mediated retinal function. Retinal pigmentary changes consisting of irregular clumping and areas of hypopigmentation are evident in the macular and perimacular areas and sometimes beyond. Most patients eventually become blind. Systemic Features: Scalp hair loss occurs during the first months of life but the alopecia does not affect eyebrows or eyelashes unlike that seen in the EEM disorder (225280) which in addition has digital and dental anomalies. Partial regrowth may occur during puberty. Light and electron microscopy of hair shafts may reveal pili torti, longitudinal ridging with scaling, and fusiform beading but these are not present in all patients. GeneticsThis is an autosomal recessive disorder resulting from homozygous mutations in the CDH3 gene located at 16q22.1. EEM syndrome (225280) is an allelic disorder with similar hair and retinal features plus dental, digital and limb anomalies. The hypotrichosis also involves the eyebrows and eyelashes in this disorder, however. Pedigree: Autosomal recessiveTreatmentTreatment Options: There is no known treatment for this disorder. ReferencesArticle Title: Hypotrichosis and juvenile macular dystrophy caused by CDH3 mutation: A candidate disease for retinal gene therapy Singh MS, Broadgate S, Mathur R, Holt R, Halford S, MacLaren RE. Hypotrichosis and juvenile macular dystrophy caused by CDH3 mutation: A candidate disease for retinal gene therapy. Sci Rep. 2016 May 9;6:23674. PubMed ID: 27157923 Hypotrichosis with juvenile macular dystrophy: clinical and electrophysiological assessment of visual function 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 May;113(5):841-7.e3. PubMed ID: 16650681 A missense mutation in CDH3, encoding P-cadherin, causes hypotrichosis with juvenile macular dystrophy Indelman M, Bergman R, Lurie R, Richard G, Miller B, Petronius D, Ciubutaro D, Leibu R, Sprecher E. A missense mutation in CDH3, encoding P-cadherin, causes hypotrichosis with juvenile macular dystrophy. J Invest Dermatol. 2002 Nov;119(5):1210-3. PubMed ID: 12445216 Read more about Hypotrichosis with Juvenile Macular Degeneration
Hypotrichosis and juvenile macular dystrophy caused by CDH3 mutation: A candidate disease for retinal gene therapy Singh MS, Broadgate S, Mathur R, Holt R, Halford S, MacLaren RE. Hypotrichosis and juvenile macular dystrophy caused by CDH3 mutation: A candidate disease for retinal gene therapy. Sci Rep. 2016 May 9;6:23674. PubMed ID: 27157923
Hypotrichosis with juvenile macular dystrophy: clinical and electrophysiological assessment of visual function 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 May;113(5):841-7.e3. PubMed ID: 16650681
A missense mutation in CDH3, encoding P-cadherin, causes hypotrichosis with juvenile macular dystrophy Indelman M, Bergman R, Lurie R, Richard G, Miller B, Petronius D, Ciubutaro D, Leibu R, Sprecher E. A missense mutation in CDH3, encoding P-cadherin, causes hypotrichosis with juvenile macular dystrophy. J Invest Dermatol. 2002 Nov;119(5):1210-3. PubMed ID: 12445216