A family from Turkey with Hay Wells Syndrome resulting from heterozygous mutation of TP 63 gene

Esra Ataman, Sukru Candan, Margherita Silengo
1.525 412

Öz


Amaç: Ankyloblepharon–ectodermal dysplasia–clefting (AEC) sendromu olarak da bilinen Hay Wells nadir bir otozomal dominant genetik sendromudur. Başlıca özellikleri ankiloblefaron (Göz kapaklarının füzyonu), ektodermal displazi ve örofasiyal yarıklanmadır. P63 geninin heterozigot mutasyonlarının bu sendroma yol açtığı bilinmektedir. Bu sendromu hatırlatan ankiloblefaron, yarık damak ve dismorfik yüz görünümüyle bu sendromu hatırlatan 2 aylık bir erkek çocuğu kliniğimize danışılmıştır. Bulgular: Fizik muayenede ektodermal displazi bulgularını gözlemlediğimizde Hay Wells sendromu ön tanısını koyduk. Aile öyküsünde bebeğin babasının ayaklarında yarıklanma ve mental retardasyonu olduğunu öğrendik. Baba ve oğlunun DNA sekans analizi Turin’de yapıldı. Her ikisinde de heterozigot bir c.1553G>T mutasyonu bulundu. Sonuç: Aile öyküsü alındığında ebeveynden birinde de hastalığın hafif bulgularının olabileceği gözden kaçırılmamalı ve nadir genetik hastalıkların tanısında akla gelmelidir. Yazıda bu gendeki mutasyonların bazı benzer sendromlara da yol açabileceğini vurguladık. Ectodermal dysplasia may present as dry skin, scarce hair, dystrophic nails, hypoplastic teeth and lacrimal duct obstruction. There may be lip and/or palate clefting (6). Advanced studies have demonstrated that mutations in the p63 gene cause this pathology. The P63 gene, also known as p51 or KET, is homologous to the tumor supressor gene (TP53) (1). Heterozygous mutations of the p63 gene cause 6 different syndromes with various combinations of ectodermal dysplasia, orofacial clefting and skeletal malformations: Hay Wells syndrome, Rapp-Hodgkin syndrome, BowenArmstrong (EEC) syndrome ADULT (acro–dermato–ungual- lacrimal-tooth) syndrome, LADD (lacrimoauricular-dental-digital) syndrome and Isolated Split Hand/Foot Malformation (SHFM) type 4. The P63 protein transactivation domain (TA), the DNA-binding domain, the tetramerization domain, and the sterile alpha domain (SAM) (1). It was shown that mutaions in the DNA-binding domain cause EEC syndrome, and mutations in the SAM domain cause Hay Wells syndrome (1, 7, 8). The Hay Wells syndrome and the Rapp Hodgkin syndrome are similar and share different findings of the same clinical entity (8, 9). These ankyloblepharon filiforme adnatum (fusion of the eye lids), severe skin erosions, abnormal hair structure (pili torti/pili canaliculi, scarce hair) and cleft palate (may be combined with cleft lip). Severe skeletal

Anahtar kelimeler


AEC, ectodermal dysplasia, autosomal dominant, p63 gene

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Referanslar


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