Dermatology Online Journal

Ectrodactyly, Ectodermal dysplasia, and Cleft lip-palate (EEC) syndrome without clefting: A rare case report
Dipali Malvankar MBBS, S Sacchidanand MD, M Mallikarjun MD
Dermatology Online Journal 18 (2): 5

Department of Dermatology, Bangalore Medical College and Research Institute, Bangalore, India

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Abstract

Ectrodactyly, Ectodermal dysplasia, and Cleft lip-cleft palate (EEC) syndrome is a rare ectodermal dysplasia presenting with various combinations of its three components. It is an autosomal dominant disorder with variable expression and penetrance. Patients have features of ectodermal abnormalities and a split hand/foot deformity of the limbs. We report a case of this rare disorder in a 40-year-old male who had ectrodactyly, ectodermal dysplasia, but no clefting of lips or palate.

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Introduction

Ectrodactyly, Ectodermal dysplasia, and Cleft lip-palate (EEC) syndrome, as the name suggests consists of ectrodactyly, i.e., limb defects, features of ectodermal dysplasia, and clefting of lips or palate. It is an autosomal dominant disorder with variable penetrance. Hence, the above features present with variable combinations with reported cases having absent clefting or absent ectrodactyly. We report a sporadic case of this disorder in a 40-year-old male who had the classical split-hand/split-foot malformation of all 4 limbs and ectodermal abnormalities, but without clefting.

Case report

A forty-year-old male patient came to the dermatology outpatient department for skin deformities. The patient was born of a non-consanguineous marriage and had skin lesions since birth. He also complained of decreased vision in both eyes since the age of 10. There was no history of absent or decreased sweating. No similar complaints were noted in the family.

Figure 1	Figure 2

On examination, he was found to have split-hand/split-foot malformation of all 4 limbs. Both upper limbs showed fusion of first 2 digits with absent third digit (Figures 1 and 2).

Figure 3	Figure 4

Lower limbs showed absent second and third toes with fusion of fourth and fifth toes.

Figure 5	Figure 6

Further cutaneous examination revealed that the patient had dystrophic nails in all digits (Figure 5). The skin of the patient appeared wrinkled. He had supernumerary nipples on both sides (Figure 6) and multiple lentigines over the back.

Figure 7	Figure 8

The oral cavity showed an enlarged bluish tongue with bluish discoloration of the buccal mucosa (Figure 7). However, cleft lip and cleft palate were conspicuously absent. His teeth were normal. The hair on the scalp was hypopigmented. However, hair elsewhere was normal.

The patient’s main complaints were ophthalmological, decreased vision in both eyes. Ophthalmological examination revealed keratitis with corneal opacity, lacrimal duct stenosis, trichiasis, and photophobia (Figure 8).

Blood investigations including complete blood count, liver enzymes, and renal parameters were normal. Ultrasound of the abdomen and hearing and cardiac assessments were normal.

The patient was managed conservatively for his dermatological and ophthalmological problems.

Discussion

A. Definition

Ectrodactyly, Ectodermal dysplasia and Cleft lip-palate (EEC) syndrome (OMIM number 129900) is a rare complex multiple anomaly syndrome having abnormalities of both ectodermal and mesodermal structures. It was first described by Cockayne in 1936. The acronym EEC was coined by Rudiger et al in 1970 [1].

B. Etiology

EEC is an autosomal dominant disorder with variable expression and penetrance [2]. However, sporadic cases like ours have also been reported. Although the classical syndrome has all three components, the presence of all three is not obligatory for diagnosis. Thus, cases without ectrodactyly have been reported [3, 4, 5] as have cases without clefting [6, 7].

The disorder is caused by mutations in the p63 gene, which is a tumor suppressor transcription factor and a member of the p53 gene family [8, 9]. It is considered the prototype of several p63 conditions including ankyloblepharon-ectodermal dysplasia-clefting (AEC or Hay-Wells) syndrome, acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome, and Rapp-Hodgkin syndrome (RHS), amongst others. All these disorders include ectodermal dysplasia, orofacial clefting, and limb malformations in variable combinations and severity [10, 11].

C. Clinical features

The typical components of EEC syndrome are: Ectrodactyly (also termed as split-hand/split-foot malformation) – abnormalities of digits in the form of absence of one or more digits and/or syndactyly; Ectodermal dysplasia – abnormal teeth especially secondary dentition, decreased sweating, dystrophic nails, and dry, sparse, hypopigmented hair; and cleft lip and/or palate. The term “lobster claw deformity” was earlier used to refer to the limb changes in this disorder but its use is now discouraged owing to its offensive nature.

A literature study on EEC syndrome found that isolated cases are more severely affected than familial cases [12]. Lacrimal duct abnormalities were also considered as a major criterion in one study [13]. Ophthalmological abnormalities include entropion, hypertelorism, absence of lacrimal puncta, hypotrichiasis, blepharitis, photophobia, corneal opacification, and dacryocystitis [14]. Genitourinary abnormalities are also reported in some patients [15, 16]. Conductive hearing loss when present is usually associated with clefting [12].

D. Differential diagnosis

The differential diagnosis of this syndrome consists of conditions that present with split-hand/split-foot malformation, clefting of lips and/or palate, and ectodermal dysplasias.

Split-hand/split-foot malformation (SHFM), also known as ectrodactyly, is a congenital limb malformation, characterized by a deep median cleft of the hand and/or foot associated with the absence of the central rays [11]. The conditions that present with split-hand/split-foot malformation are given in Table 1.

Acro-cardio-facial syndrome (ACFS) is a rare genetic disorder characterized by split-hand/split-foot malformation (SHFM), facial anomalies, cleft lip/palate, congenital heart defect (CHD), genital anomalies, and mental retardation [17]. However, no evidence of heart disease or abnormal genitalia was found in our patient.

Hay-Wells syndrome is another entity in the differential diagnosis. In this syndrome, the main features are ankyloblepharon filiforme adnatum, ectodermal defects, and cleft lip/palate. Of these 3 features, only ectodermal dysplasia was found in our patient and ectrodactyly is not seen in Hay-Wells syndrome [18].

Rapp-Hodgkin syndrome is characterized by stiff, sparse, wooly hair, sparse eyebrows and lashes, cleft palate, absence of lacrimal punctae, epiphora, decreased sweat glands, and dystrophic nails. However, ectrodactyly is not a feature of this syndrome [19].

Acro-Dermato-Ungual-Lacrimal-Tooth (ADULT) syndrome is characterized by ectrodactyly, syndactyly, fingernail and toenail dysplasia, hypoplasia of the breast and nipple, excessive freckling, lacrimal duct atresia, frontal alopecia, primary hypodontia, and/or early loss of permanent teeth [20]. However, the teeth in our patient were normal.

E. Management

The management of EEC syndrome, like any other ectodermal dysplasia, requires a multidisciplinary approach involving a dermatologist, plastic surgeon, dental surgeon, ophthalmologist, and renal specialist. Reconstructive surgery for the dermatological, oral, and ophthalmological conditions will improve the quality of life. Genetic counseling should be offered to families of those affected [13]. Prenatal diagnosis using cleft lip and palate as a marker can be done in the case of families with affected children [21].

References

1. Rudiger RA, Haase W, Passarge E. Association of ectrodactyly, ectodermal dysplasia and cleft lip-palate-the EEC syndrome. Am J Dis Child. 1970 Aug;120(2):160-3. [PubMed]

2. Penchaszadeh VB, de Negrotti TC. Ectrodactyly- ectodermal dysplasia-clefting (EEC) syndrome: dominant inheritance and variable expression. J Med Genet. 1976 Aug;13(4):281-4. [PubMed]

3. Sankhyan N, Kaushal RK, Sarin S. Ectodermal dysplasia, ectrodactyly, cleft lip/palate syndrome without ectrodactyly. Dermatol Online J. 2006 May 30;12(4):5. [PubMed]

4. Kuster W, Majewski F, Meinecke P. EEC syndrome without ectrodactyly? Report of 8 cases. Clin Genet. 1985 Aug;28(2):130-5. [PubMed]

5. Fryns JP, Legius E, Dereymaeker AM, Van den Berghe H. EEC syndrome without ectrodactyly: report of two new families. J Med Genet. 1990 Mar;27(3):165-8. [PubMed]

6. Wallis CE. Ectrodactyly (split-hand/split-foot) and ectodermal dysplasia with normal lip and palate in a four-generation kindred. Clin Genet. 1988 Oct;34(4):252-7. [PubMed]

7. Thakkar S, Marfatia Y. EEC syndrome sans clefting: Variable clinical presentations in a family. Indian J Dermatol Venereol Leprol. 2007 Jan-Feb;73(1):46-8. [PubMed]

8. Barrow LL, van Bokhoven H, Daack-Hirsch S, Andersen T, van Beersum SE, Gorlin R, et al. Analysis of the p63 gene in classical EEC syndrome, related syndromes, and non-syndromic orofacial clefts. J Med Genet. 2002 Aug;39(8):559-66. [PubMed]

9. Ergin H, Semerci CN, Karakus YT, Scheffer H, Ergin S, Koltuksuz U, et al. The EEC syndrome and SHFM: report of two cases and mutation analysis of p63 gene. Turk J Pediatr. 2010 Sep-Oct;52(5):529-33. [PubMed]

10. Celik TH, Buyukcam A, Simsek-Kiper PO, Utine GE, Ersoy-Evans S, Korkmaz A, et al. A newborn with overlapping features of AEC and EEC syndromes. Am J Med Genet A. 2011;155A(12):3100-3 [PubMed]

11. Duijf PH, van Bokhoven H, Brunner HG. Pathogenesis of split-hand/split-foot malformation. Hum Mol Genet. 2003 Apr 1;12 Spec No 1:R51-60. [PubMed]

12. Roelfsema NM, Cobben JM. The EEC syndrome: a literature study. Clin Dysmorphol. 1996 Apr;5(2):115-27. [PubMed]

13. Buss PW, Hughes HE, Clarke A. Twenty-four cases of the EEC syndrome: clinical presentation and management. J Med Genet. 1995 Sep;32(9):716-23. [PubMed]

14. Kumar HN, Kugar TS, Rao RJ, Kodkany S. EEC syndrome. Indian J Ophthalmol. 2007 Mar-Apr;55(2):162-3. [PubMed]

15. Rollnick BR, Hoo JJ. Genitourinary anomalies are a component manifestation in the ectodermal dysplasia, ectrodactyly, cleft lip/palate (EEC) syndrome. Am J Med Genet. 1988 Jan;29(1):131-6. [PubMed]

16. London R, Heredia RM, Israel J. Urinary tract involvement in EEC syndrome. Am J Dis Child. 1985 Dec;139(12):1191-3. [PubMed]

17. Digilio MC, Dallapiccola B. Acro-cardio-facial syndrome. Orphanet J Rare Dis 2010;5:25. [PubMed]

18. Julapalli MR, Scher RK, Sybert VP, Siegfried EC, Bree AF. Dermatologic findings of ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome. Am J Med Genet A 2009 Sep;149A(9):1900-6. [PubMed]

19. Tosun G, Elbay U. Rapp-Hodgkin syndrome: clinical and dental findings. J Clin Pediatr Dent 2009;34(1):71-5. [PubMed]

20. Reisler TT, Patton MA, Meagher PP. Further phenotypic and genetic variation in ADULT syndrome. Am J Med Genet A 2006;140(22):2495-500. [PubMed]

21. Anneren G, Andersson T, Lindgren PG, Kjartansson S. Ectrodactyly-ectodermal dysplasia-clefting syndrome (EEC): the clinical variation and prenatal diagnosis. Clin Genet. 1991 Oct;40(4):257-62. [PubMed]

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