J Med Genet: first published as 10.1136/jmg.20.1.52 on 1 February 1983. Downloaded from

Journal ofMedical Genetics, 1983, 20, 52-57 Association of ectodermal dysplasia, ectrodactyly, and macular dystrophy: the EEM syndrome

SHOZO OHDO, KIYOTAKE HIRAYAMA, AND TAMOTSU TERAWAKI From the Department ofPediatrics, Miyazaki Medical College; the Department ofPediatrics, Faculty ofMedicine, Ryukyu University; andthe Department ofPediatrics, Faculty ofMedicine, Kagoshima University, Japan.

SUMMARY We report five patients with ectodermal dysplasia, ectrodactyly associated with syndactyly or cleft hand or both, and, in addition, macular dystrophy which was presumed to be progressive, in an isolated population on a remote island in Japan. The heredity of this syndrome was thought to be autosomal recessive. Three cases have been reported so far with a combination of the same abnor- malities. The parents in these cases were consanguineous.' 2

Among the syndromes of ectodermal dysplasia we first examined her. Her parents were first cousins associated with malformations of the extremities, and had no signs of ectrodactyly or ectodermal there are Roberts's syndrome,' EEC syndrome,4 the dysplasia. Her two sibs were healthy. syndrome reported by Robinson et al,5 the syndrome On physical examination, her hair was very sparse, reported by Freire-Maia,6 and the syndrome reported thin, and short and the eyebrows and eyelashes werecopyright. by Bowen and Armstrong.7 However, these also sparse and thin (fig 2). Her teeth were small and syndromes clearly differ from the syndrome described widely spaced, numbering 25 in all. Cardiac murmur in this paper, because they lack the characteristic was not heard. Development of the breasts, axillary findings in the ocular fundus. hair, and pubic hair was normal. On her right hand, the second finger was missing, and the third finger Case reports consisted of only the proximal phalanx. Campto- dactyly was noted in the first, fourth, and fifth http://jmg.bmj.com/ CASE I fingers. On her left hand, the second finger was The proband (V * 1, fig I) was a 1 61-year-old girl when missing, the third finger had no distal phalanx, and Received for publication 12 June 1982. the fourth finger had neither the distal phalanx nor on September 24, 2021 by guest. Protected

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Association ofectodermal dysplasia, ectrodactyly, and macular dystrophy 53

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I .4. the distal portion of the middle phalanx. Further- attributable diagnostically to the combination of more, x-ray showed syndactyly between 'he third polydactyly and syndactyly (fig 3). The toes on her had fourth fingers (fig 3). On her right foot, the distal left foot were normal. phalanx of the second toe was divided into two, In her ocular fundi (fig 4), retinochoroidal atrophy

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FIG 3 (a) Dorsal aspect of the hands, (b) x-ray of the hands,(c) the right foot,and (d) x ray of the right foot of the proband. J Med Genet: first published as 10.1136/jmg.20.1.52 on 1 February 1983. Downloaded from

54 Shozo Ohclo, Kiyotake Hirayatia, anid Tamiiotslu Terawaki

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FIG 5 (a) Front view, (b) hands, (c) right foot, and (d) ocularfundus ofcase 2. was observed in the macular region. Four small areas examined her. She was illegitimate. Though her (1/4 disc size) of pigment mottling of yellowish-white father was not known, it was rumoured that he was colour were noted in the retinal deep layer around one of the villagers. She was a first cousin once the fovea. The peripheral retina and vessels were removed of the proband.

normal. Ths test for colour vision revealed Her clinical features were similar to those of thecopyright. deuteranomalopia. proband. The distal phalanx of the second finger of The sweat test was normal, IQ was 98 as deter- both hands was missing, but her toes were normal. mined by the WAIS method, and the lymphocyte In the fundi, extensive retinochoroidal atrophy karyotype was normal. centring on the macula was observed, within which pigment mottling was scattered (fig 6). She refused CASE 2 further examination and photographs. V*6 (fig 1) was a girl aged 10 years 8 months when we examined her. Her parents were distantly related and CASE 4 http://jmg.bmj.com/ had no malformations or visual disturbance. Her IV- 3 (fig 1) was a 45-year-old man when we examined two sisters were healthy. She is a second cousin of him. He is a second cousin of the proband and his the proband. were the parents were distantly related. Although they Her height and weight were within normal dead, we were told that they had no ectrodactyly or range. Her hair was very sparse, thin, and short visual disturbance. He had six sibs, of whom two (fig 5). She had 19 teeth in total which were widely brothers showed the same malformations as he. spaced. Breast development was normal for her age. However, one of them (IV- 7, fig 1) had died in on September 24, 2021 by guest. Protected No cardiac murmur was heard. On her right hand, the second finger was missing infancy. from the proximal interphalangeal joint, and the His physique was normal. His hair was hardly third finger was missing from the portion corre- visible and his eyebrows and eyelashes were very sponding to the body of the proximal phalanx. On scanty (fig 7). her left hand, the second finger was missing from He had only the first and fifth fingers on each the proximal interphalangeal joint. Syndactyly hand. On the first finger of the right hand, a process between the third and fourth toes on her right foot which looked like the second finger was noted was noted (fig 5). (fig 7). On his left foot, the second toe was missing In the fundi, retinochoroidal atrophy without and syndactyly between the third and fourth toes pigment mottling was observed centring on the was observed. The fifth toe was hypoplastic. On his macula (fig 5). Sweating was normal. right foot, syndactyly between the first and second toes was detected and the third toe was missing. The CASE 3 fourth and fifth toes were hypoplastic (fig 7). IV*8 (fig 1) was a 39-year-old womani wheni we In both fundi, extensive retinochoroidal atrophy J Med Genet: first published as 10.1136/jmg.20.1.52 on 1 February 1983. Downloaded from

Association ofectodermal dysplasia, ectrodactyly, and macular dystrophy 55

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FIG 7 (a) Front view, (b) hands, (c)feet, and (d) ocularfundus of case 4. J Med Genet: first published as 10.1136/jmg.20.1.52 on 1 February 1983. Downloaded from

56 Shozo Ohdo, Kiyotake Hirayama, and Tamotsu Terawaki

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On his right hand, the second and fifth fingers were from those of the cases described in this paper. The missing. On his left hand, the second and fifth fingers findings reported by Hayakawa et a12 in 1979 of a were missing and there was syndactyly between the 30-year-old woman were similar to those of the third and fourth fingers (fig 8). The toes were present cases. The parents of this patient were first normal. cousins. The findings in the fundus were similar to those in Ifwe add together the cases reported by Albrectsen case 4 (fig 8). and Svendsen,1 by Hayakawa et al,2 and those in thecopyright. present report, the number of male patients is three Discussion and the number of female patients is five. All their parents were consanguineous. Consequently, we The cases described in this paper show characteristic attribute the aetiology to an autosomal recessive combinations of the following congenital trait. abnormalities. The isolated population in which the authors found were very (1) The hair, eyebrows, and eyelashes the present cases started with 30 families some 300 http://jmg.bmj.com/ sparse. Partial anodontia was observed and the years ago. These 30 families originated from three teeth were small. families living in a very remote village. Thereafter, (2) Ectrodactyly associated with syndactyly or consanguineous marriages among the villagers have cleft hand or both was noted. been common. Although the authors have been (3) Macular dystrophy presumed to be progressive conducting surveys on this isolated population since was observed in the ocular fundus. Within the range 1964, no new patient with the same abnormalities of the macular dystrophy, pigment mottling was has appeared. We feel that the reason for this is that scattered. The retina in the periphery and the vessels the youth are now leaving the island to find on September 24, 2021 by guest. Protected in the fundus were normal. These findings are employment in the cities, thus avoiding con- similar to those found in central and pericentral sanguineous marriages. retinopathia pigmentosa. These findings were observed in all five cases References examined by us. There were no other members of this isolated community who had signs of ecto- Albrectsen B, Svendsen IB. Hypotrichosis, syndactyly, dermal dysplasia or of ectrodactyly. and retinal degeneration in two siblings. Acta Derm Venereol 1956;1:96-101. The first report of cases similar to ours was made 2 Hayakawa M, Kato K, Yamauchi Y. A case of central by Albrectsen and Svendsen' in 1956. The cases and pericentral retinopathia pigmentosa with abnor- reported by them were a 4-year-old boy and his malities of hair, hands and teeth. Ganka 1979;21 :433-8. 6-year-old sister, whose parents were first cousins. 3Roberts JB. A child with double cleft of lip and palate, protrusion of the intermaxillary portion of the upper jaw They had the normal number of teeth and these and imperfect development of the bones of the four researchers did not think that the findings in the extremities. Ann Surg 1919;70:252-3. fundus were progressive. Only these findings differ 4Rudiger RA, Haase W, Passarge E. Association of J Med Genet: first published as 10.1136/jmg.20.1.52 on 1 February 1983. Downloaded from

Association of ectodermal dysplasia, ectrodactyly, and macular dystrophy 57 ectrodactyly, ectodermal dysplasia, and cleft lip-palate. 7 Bowen P, Armstrong HB. Ectodermal dysplasia, mental The EEC syndrome. AmJ Dis Child 1970; 120:160-3. retardation, cleft lip/palate and other anomalies in three 5 Robinson GC, Miller JR, Bensimon JR. Familial sibs. Clin Genet 1976;9:35-42. ectodermal dysplasia with sensori-neural deafness and other anomalies. Pediatrics 1962 ;30:797-802. 6 Freire-Maia N. A newly recognized genetic syndrome of Requests for reprints to Dr S Ohdo, Department of tetramelic deficiencies, ectodermal dysplasia, deformed Pediatrics, Miyazaki Medical College, 5200 Kihara, ears, and other abnormalities. Am J Hum Genet 1970;22: 370-7. Kiyotake-cho, Miyazaki, Japan. copyright. http://jmg.bmj.com/ on September 24, 2021 by guest. Protected