Cent. Eur. J. Med. • 7(4) • 2012 • 567-570 DOI: 10.2478/s11536-012-0013-0

Central European Journal of Medicine

A child with EEC syndrome – a 10 years follow-up

Case Report Agnieszka Machorowska-Pieniążek1, Małgorzata Muc-Wierzgoń*2, Stefan Baron1, Teresa Kokot2, Edyta Fatyga2 1 Congenital Disease Outpatient Clinic of the Chair and Department of Orthodontics, Silesian Medical University, 41-800 Zabrze, Poland

2 Faculty of Public Health, Silesian Medical University, 41-902 Bytom, Poland

Received 22 December 2011; Accepted 3 April 2012 Abstract: Ectrodactyly-ectodermal dysplasia-cleft (EEC) syndrome is a rare congenital disease, occurring in 7 per 10,000 live newborns. It runs in families as an inherited autosomal dominant; it can also occur spontaneously as a point missense mutation in the DNA- binding domain of the p63 transcription factor (TP63) gene. Clinical diagnosis of a complete EEC syndrome involves a patient who presents with ectrodactyly, ectodermal dysplasia, and cleft lip and/or palate. This paper presents outcome of 10 years of interdisciplinary therapy for an EEC child with special consideration of the facial presentation of the disease. The management of cases of EEC syndrome requires multidisciplinary action because of the great variability in clinical expression. In an individual patient, treatment should be based on clinical findings and symptoms. Early interdisciplinary therapy will allow a patient with EEC syndrome to reinstate oral functions, satisfactory appearance, and social integration. Keywords: EEC syndrome • Interdiscyplinary therapy • 10 years follow-up © Versita Sp. z o.o

1. Introduction EEC3 – are distinguished. A classic, phenotypically overt EEC3 syndrome is caused by a TP63 mutation in Ectrodactyly-ectodermal dysplasia-cleft (EEC) chromosome 3q27. A clinical diagnosis of a complete syndrome is a familial, autosomal dominant anomaly, EEC syndrome is made when a patient presents or it may occur spontaneously as a point missense ectrodactyly, ectodermal dysplasia, and cleft lip and/or mutation in DNA-binding domain of the p63 transcription palate [5]. Ectodermal dysplasia is characterized by thin, factor (TP63) gene. High expression of this protein is chapped, peeling, sometimes cracked, skin; thin, brittle, found in keratinocytes of the basal epidermal layer often fair hair, eyebrows and eyelashes; teeth abnormal [1,2]; it has a major role in epidermal stem cell division in number, size and/or shape (hypodontia, oligodontia and differentiation into transit-amplifying cells. It is or anodontia, conical or peg-like teeth); enamel also a signal protein in transcription of many factors hypoplasia, and is often accompanied by abnormalities important for epidermal development and homeostasis, of sudoriferous glands and nail dystrophy. Ectrodactyly is including P-cadherin, the chief hair development hand and foot malformation with total or partial atrophia regulator; bone morphogenesis protein; fibroblast of the central line of digits, clinically presenting as a cleft growth factor; transforming growth factor B; and others that sometimes reaches to the wrist. Fingers adjacent [1,3,4]. Depending on locus of the mutated TP63 gene to the cleft may show camptodactyly, syndactyly, or and combination of dysmorphological features, three clinodactyly; the limb resembles a lobster claw – the subtypes of the EEC syndrome – EEC1, EEC2, and source of the common name of the malformation [6].

* E-mail: [email protected] 567 A child with EEC syndrome: a 10-year follow-up

Cleft lip and/or palate are other traits characterizing this syndrome. In addition, EEC patients may have genitourinary defects, conductional hearing impairment, nasolacrimal canal abnormalities, or mental deficits of various degrees. Roelsfema et al. developed a scoring system of disease magnitude based on coexistent signs [5]; a patient with the maximum score of 18 points has the most severe form of EEC syndrome.

2. Aim of the paper

This paper presents the outcome of 10 years of interdisciplinary therapy for an EEC child, with special consideration of the facial presentation of the disease.

3. Case report

In October 1999, a male newborn was admitted to the Department of Orthodontics of the Silesian Medical School for consultation concerning a cleft. Clinical examination of the child revealed a bilateral cleft lip and palate, accompanied by significant protraction of the premaxilla and wide fissure of the cleft (Figure 1). In addition, the newborn had malformed hands and feet, a deep cleft of upper limb metacarpi, was missing II and III digits of the right hand and III digit of the left hand, had syndactyly of digits IV and V of the right hand and syndactyly I-II and III-IV of the left hand. In addition, the fused digits showed camptodactyly. His skin was chapped, peeling, and cracked. The child was born full Figure 1. Newborn with EEC, bilateral cleft of the lip and palate term by vaginal delivery with head-down presentation, and had an Apgar score of 10. 2 and 6, the boy underwent several plastic surgeries of Stage I: Because the extent of the cleft made feeding the nose and both hands. difficult, a maxilla impression was taken for the palatal Stage III: The next orthodontic visit was done when plate. In addition, macerated epidermis was removed the boy was 6 years of age (2005). At that time, there from the premaxilla, and the mother was instructed in was severe caries of all the deciduous teeth, with soft, lip massage technique. A week later, the child had the hypoplastic enamel, supraocclusion with elongation palatal plate introduced, and the mother was instructed of the anterior part of the maxillary alveolar process, to keep the oral cavity, premaxilla, and plate clean. and the mandible was locked in the posterior position On subsequent visits up to the third month, the palatal (Figure 2). There was also suppurative secretion in the plate was adjusted, and mouth hygiene, development of conjunctival sac, indicating lacrimal gland abnormality, occlusion, and oral functions were checked. Insufficient angular cheilitis, and a deeply fissured tongue. Condition oral hygiene was observed several times, and on two of the occlusion and teeth prevented treatment with occasions oral aphthae were found; at every visit, the orthodontic devices. Sanitation of the dental foci was mother was reminded of the need for proper care of the recommended. For the ensuing four years, the patient child’s oral cavity. did not shown in the Outpatient clinic. Stage II: At age 4 months, the boy underwent lip Stage IV: In 2009, the patient had diagnostic X-rays suturing, and at age 2 years, palatal suturing. After performed: an orthopantomogram and lateral palatal plasty, the parents did not appear for follow-up at cephalogram. Analysis of the orthopantomogram the Congenital Disease Outpatient Clinic. Between ages revealed significant defects of bone tissue in the maxillar

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Figure 2. Deciduous teeth of the patient with severe dental caries and supraocclusion alveolar process, and oligodontia of the permanent teeth he had a bilateral cleft lip and palate. Buss et al. in their 12, 15, 22, 25, 35, 34, 32, 31, 42, 44, and 45. Analysis of studies diagnosed this type of facial cleft in almost 21% the cephalogram showed that the maxilla was retracted of EEC patients [7]; Yin et al. observed both cleft lip and relative to base of the cranium (angular cheilitis, ML=19°); moreover, the maxillar base plane was curved. dental hypoplasia, and oligodontia require thorough oral A clinical occlusion examination revealed bilateral hygienic procedures performed on the patient, and this crossbite and negative overjet. The orthodontic therapy is possible only if the patient has certain degree of motor plan included preliminary arrangement of the teeth in and mental fitness [6,10]. Hand malformation is not a the maxilla and its expansion with fixed orthodontic significant limitation of manual skill. Both our studies and appliances. This first stage of therapy aims to prepare literature reviews show that patients with ectrodactyly the alveolar arch for bone implant to the maxilla alveolar may have very precise grip and well-developed muscles process. At present, the patient is 10 years of age and of the thumb and opposed fingers, which indicates very is undergoing the first stage of orthodontic treatment, good environmental adaptation. It is mental disability that which is to be followed by surgery and restorative limits self-reliance, social integration, and environmental denture preparation (Figure 3). The digits in syndactyly adaptation. According to Roelfsema et al., this is the of the both the patient’s hands were surgical separated, case in 6.5% of EEC patients, whereas Buss et al. did but foot surgery is incomplete. not find this trait in the examined patients who graduated from regular schools and worked various jobs [5,7]. The boy described herein presents a very slight intellectual 4. Discussion deficit, which isn’t a severe handicap and allows him to have a ‘normal’ life. The boy who presented with EEC had 17 of the possible EEC syndrome is known to be a familial disorder 18 points in the disease magnitude score according to [1,2,8,9]. The patient’s mother has ectrodactyly, nail Roelsfema et al. [5]. In addition to ectodermal dysplasia, plate hypoplasia, thin, brittle hair, and no buds of both

569 A child with EEC syndrome: a 10-year follow-up

upper incisors, therefore she does not present all traits of the syndrome:10/18 points according to the scale of Roelsfema et al. [5] The father is healthy. The aforementioned dysmorphological traits may indicate partial penetration of the syndrome in the patient’s mother or another nosological entity of the TP63 gene mutation family of congenital diseases. Literature review confirms that the same TP63 gene mutations may produce various clinical symptoms [11], and according to Clements et al. [1], the genotype-phenotype relationship in this indicates that additional genes-modulators or epigenetic factors influence phenotypic expression of the syndrome. Despite categorization problems, clinical diagnosis of the syndrome does not require genetic confirmation, and the role of the physician is to detect all associated abnormalities, and by implementing interdisciplinary and longitudinal medical care, address all the patient’s individual therapeutical needs.

5. Conclusions

Because of the great variability in clinical expression, the management of cases of EEC syndrome requires mul- tidisciplinary action. In an individual patient, treatment Figure 3. A - Before preliminary arrangement of the teeth in the maxilla and its expansion with fixed orthodontic should be based on clinical findings and symptoms. appliances; B - after first phase of orthodontics Early interdisciplinary therapy will allow the patient with treatment EEC syndrome to reinstate oral functions, satisfactory appearance, and social integration.

References

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