Novel missense mutation of the TP63 gene in a newborn with Hay-Wells/Ankyloblepharon-Ectodermal defects-Cleft lip/palate (AEC) syndrome: clinical report and follow-up

• Published in: Italian journal of pediatrics Vol. 47; no. 1; p. 196
• Main Authors: Serra, Gregorio, Antona, Vincenzo, Giuffré, Mario, Li Pomi, Federica, Lo Scalzo, Lucia, Piro, Ettore, Schierz, Ingrid Anne Mandy, Corsello, Giovanni
• Format: Journal Article
• Language: English
• Published: England BioMed Central 28.09.2021; BMC
• Subjects: AEC syndrome; Alopecia; Amino acids; Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome; Antibiotics; Baldness; Birth defects; Case Report; Chromosome 3; Cleft Lip - genetics; Cleft lip/palate; Cleft Palate - genetics; Congenital diseases; Congenital skin disorders; Dermatitis; Dysplasia; Ears & hearing; Ectodermal dysplasia; Ectodermal Dysplasia - genetics; Exocrine glands; Eye Abnormalities - genetics; Eyelids - abnormalities; Female; Genetic screening; Genotype & phenotype; Hair; Hay-Wells syndrome; Humans; Infant, Newborn; Medical screening; Missense mutation; Mutation; Mutation, Missense; Neonates; Patients; Phenotypes; Proteins; Reconstructive surgery; Scalp; Sequence analysis; Skin; Skin care products; Teeth; Transcription factors; Transcription Factors - genetics; Tumor protein p63 gene; Tumor Suppressor Proteins - genetics; Tumors; AEC syndrome; Tumor protein p63 gene; Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome; Congenital skin disorders; Hay-Wells syndrome; Ectodermal dysplasia
• ISSN: 1824-7288; 1720-8424; 1824-7288
• DOI: 10.1186/s13052-021-01152-y

Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome, also known as Hay-Wells syndrome, is a rare genetic syndrome with ectodermal dysplasia. About 100 patients have been reported to date. It is associated to a heterozygous mutation of the tumor protein p63 (TP63) gene, located on chromosome 3q28. Typical clinical manifestations include: filiform ankyloblepharon adnatum (congenital adherence of the eyelids), ectodermal abnormalities (sparse and frizzy hair, skin defects, nail alterations, dental changes and hypohidrosis), and cleft lip/palate. Diagnostic suspicion is based on clinical signs and confirmed by genetic testing. We hereby report on a female newborn with erythroderma, thin lamellar desquamations, extensive skin erosions, sparse and wiry hair, filiform ankyloblepharon adnatum, agenesis of the lachrymal puncta, cleft palate and nail dysplasia. Her phenotype was compatible with AEC syndrome. Then, based on the clinical suspicion, sequencing analysis of the TP63 gene was performed, and revealed a de novo novel missense mutation. Eyelids adherence and cleft palate underwent surgical correction, while skin erosions were treated with topical antibiotics/antifungals and emollient/re-epithelizing creams. A surgical reconstruction is presently planned for the agenesis of the lachrymal puncta. The infant currently is 17 months of age and is included in a multidisciplinary follow-up. At present shows growth impairment and mild developmental delay, and typical signs of ectodermal dysplasia with small areas of dermatitis lesions on the scalp, without further abnormalities. Our report underlines the relevance of an early and careful clinical evaluation in neonates with ankyloblefaron, facial dysmorphism, and signs of ectodermal dysplasia. In these cases, the suspicion of AEC syndrome must be promptly raised, and sequencing analysis of TP63 early performed as well. An individualized, multidisciplinary and long-term follow-up should be guaranteed to affected subjects and their families, also to identify associated morbidities and prevent possible serious complications and adverse outcomes.