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

Abstract

Introduction 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. Patient’s presentation 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. Conclusions 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.

Novel mutations of the ABCA12, KRT1 and ST14 genes in three unrelated newborns showing congenital ichthyosis

“…It includes topical emollients, protective padding, and keratolytic agents. Differential diagnosis includes skin disorders (EB, ichthyosis bullosa of Siemens, ichthyosis hystrix , and peeling skin syndrome), genetic diseases causing neonatal blistering (i.e., incontinentia pigmenti , and Ankyloblepharon–Ectodermal defects–Clef lip/palate syndrome) [ 18 ], and other conditions acquired early in life (as SSSS, bullous impetigo , Stevens–Johnson syndrome, and toxic epidermal necrolysis). In our Patient 2, target NGS revealed a novel variant of the KRT1 gene, mapping on chromosome 12q13.13, not reported in literature.…”

Quality of life improving after propranolol treatment in patients with Infantile Hemangiomas

“…Our observations confirm that an early management of patients with IH has a positive impact on the therapeutic effectiveness, and is able as well to prevent the worsening of IH-related QoL [ 2 , 10 ]. The treatment of IH in reference centers seems to improve diagnostic and therapeutic results [ 11 , 12 ], and may help parents to a better understanding of the disease, including both diagnostic course and therapy. Moreover, it allows parents to share personal experiences with other families living similar conditions [ 13 ].…”

Novel de novo missense mutation in the interferon regulatory factor 6 gene in an Italian infant with IRF6-related disorder

“…Indeed, overlapping features, sometimes including neonatal hypoglycemia, warrant a more general investigation, since there are other genes of interest in the differential diagnosis of IRF6-related disorders. These should at least include: BMP4 (Orofacial cleft 11; OMIM #600,625), CDH7 (CHARGE syndrome; OMIM #214,800), FGF8 (hypogonadotropic hypogonadism 6; OMIM #612,702), FGFR1 (FGFR1-related hypogonadotropic hypogonadism; OMIM #147,950), GRHL3 (VWS2; OMIM #606,713), KDF1 (Ectodermal dysplasia 12; OMIM #617,337), KMT2D / KDM6A (Kabuki syndrome; OMIM #147,920/#300,867), MSX1 ( MSX1-Related Disorders like Ectodermal dysplasia 3; OMIM #189,500), OFD1 (OFD1; OMIM #311,200), RIPK4/CHUK (Bartsocas-Papas syndrome; OMIM #263,650/#619,339), TFAP2A (branchio-oculo-facial syndrome; OMIM #113,620), and TP63 (TP63-related disorders like Hay-Wells syndrome; OMIM #603,273) [ 16 , 18 , 19 ]. Interestingly, it has been reported an Italian girl with cooccurrence of clinical diagnosed Kabuki syndrome and VWS [ 20 ].…”