Ophthalmological findings in ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome: a case report

| We report on a case of two sisters, daughters of consanguineous parents, presenting with a similar condition of low visual acuity associated with retinal dystrophy in both eyes associated with alopecia and bone alterations or syndactyly.


INTRODUCTION
In 1956, Albrectsen and Svendsen described two siblings of consanguineous parents presenting with syndactyly, sparse hair, and retinal degeneration with normal psy chomotor development (1) .
Ectodermal dysplasia, ectrodactyly, and macular dys trophy (EEM) syndrome results from mutation of the CDH3 gene (MIM 114021), which decodes the classical Pcadherin molecule (2) . Cadherins are integral membrane glycoproteins responsible for calciumdependent inter cellular adhesion wherein the CDH3 protein manifests in a variety of tissues, including follicular capillaries, retinal pigment epithelium, and limb development (3,4) . EEM syndrome is characterized by scarce hair at birth with little growth during the patients' life, and some pa tients may have dental anomalies. Limb malformations may present significant phenotypic variability among previously reported cases (5,6) . Macular dystrophy de velops with significant progressive loss of visual acuity between the ages of 16 and 20 years (6) .
Fundoscopy may not show clinically visible changes early in the course of EEM syndrome, yet it progresses with deterioration of the retinal pigment epithelium and atrophic areas in the macular region. In addition, middle periphery hyperpigmentation, white deposits, and an orange peel appearance may be observed. Electroreti nographic scans may show reduced wave amplitude, revealing retinal dysfunction, and electrooculogram de monstrates normal values. In addition, the vessels, optic disc, and peripheral retina (7,8) .

CASE REPORTS Case 1 (#1 heredogram)
A 15yearold girl with consanguineous parents pre sented with low visual acuity. An ophthalmologic exa mination demonstrated acuity 20/100 (5.00 sph) and 20/150 (5.75 sph). Dry eye was diagnosed with positive Schirmer test (8 mm) along with decreased BUT in both eyes. Fundoscopy demonstrated pigmentary alteration in the macular region of both eyes. During anamnesis, the patient reported hair loss since childhood, for which she wore a wig, in addition to a procedure for corrective repair of syndactyly between 2° and 3° for right chiro dactyl (Figures 1 and 2).

Case 2 (#3 heredogram)
A female child aged 9 years, the sister of patient 1, presented with low visual acuity of 20/80 (LP) in the right and 20/100 (LP) in the left eye. We performed bio microscopy and tonometry with no observed changes, and no signs of dry eye were diagnosed. Fundoscopy revealed hypopigmented macular lesions in both eyes with capillary rarefaction and syndactyly between the second and third pododactyls (Figures 3 and 4).

DISCUSSION
EEM syndrome is an autosomal recessive disease requi ring a copy of the defect among the parents of the affec ted individual with a high incidence in blood relatives (9) .
The CDH3 gene encoding the Pcadherin protein con tains 16 exons on human chromosome 16q22.1 (2) , and it is known that the mutation contains the intragenic deletion of exons 12 and 13, resulting in continuous transcription of exon 11 to exon 14 and, while maintaining the structu re, loss of functionality occurs in the future protein (10) . In addition, CDH3 gene mutations are also responsible for hypotrichosis associated with juvenile macular dystrophy   and may represent phenotypic heterogeneity of the same syndrome (11,12) . Both conditions are similarly associated with thin and sparse hair accompanied with macular Arq Bras Oftalmol. 2018;81(5):440-2 dystrophy; however, individuals with EEM develop mal formations of the hands and feet (11,13) .
In the cases presented, the changes in patient 1, such as hypotrichosis and macular dystrophy, are more evi dent. Optical coherence tomography revealed macular alterations. The patient underwent corrective surgery for syndactyly. Patient 2, who was younger, presented a milder but evolving condition after 2year followup assessment where the syndactyly was not corrected. In addition, electroretinogram is not available in our city, but the retinal findings were characteristic of the dystro phy reported in the literature.
Only the older sister was diagnosed with signs of dry eye, perhaps because her alopecia and retinal symptoms were more severe or her younger sister had not yet pre sented.
The patients reported similar alterations in their de ceased sister (#2 heredogram), who died because of unknown causes; their brother did not have alterations. Both of our patients were referred for dermatological followup. This ophthalmologic pathology, for which no available treatment can control the evolution of low visual acuity, may lead to bilateral blindness.