EEC-LM-ADULT syndrome caused by R319H mutation in TP63 with ectrodactyly, syndactyly, and teeth anomaly

Abstract

Rationale: Ectrodactyly ectodermal dysplasia-cleft lip/palate (EEC) syndrome, limb-mammary syndrome (LMS), and acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome are caused by a TP63 gene disorder and have similar features. In the present article, a R319H mutation in TP63 is reported, and the correlation between genotype and phenotype is discussed based on the current case and previous literature. Patient concerns: A 13-year-old Japanese boy had ectrodactyly in the right hand and left foot and syndactyly in the left and right foot, and tooth shape abnormalities. Diagnoses: Peripheral blood samples were obtained, and mutation analysis was performed. A heterozygous G>A transition at cDNA position 956 of the TP63 gene was found. The patient was diagnosed with ELA (EEC/LM/ADULT) syndrome based on his clinical features and mutation analysis results. Interventions: The patient underwent surgery to correct the left foot malformation at 1 year of age and the right foot syndactyly at 11 years of age. Outcomes: No complications were observed after the first and second operations. He can walk comfortably after them, and no additional interventions will be planned in him. We continued to follow up with him up to the present. Lessons: The concept of ELA syndrome, which is the original concept of combining 3 syndromes (EEC syndrome/LMS/ADULT syndrome) into a unique clinical entity, can help clinicians to better understand TP63-related syndromes and improve the differential diagnosis of these syndromes.

History and highlights of the teratological collection in theNarrenturm, Vienna (Austria)

“…Moreover, it was noticed that the eyebrows and eyelashes were absent. Although dystrophic nails, diffuse scaling and palmoplantar keratoderma could not be assessed properly, the most likely diagnosis is “autosomal dominant ectrodactyly, ectodermal dysplasia, and cleft lip/palate (EEC) syndrome” (OMIM %129,900, 604,292) (Oğur & Yüksel, 1988; Otsuki et al, 2020; Sabhlok et al, 2015).…”

“…Although dystrophic nails, diffuse scaling and palmoplantar kerato- Yüksel, 1988;Otsuki et al, 2020;Sabhlok et al, 2015).…”

A Family with EEC Syndrome in the Son and ADULT Syndrome in His Father Caused by the c.797G&gt;A (p.Arg266Gln) Pathogenic Variant in the <i>TP63</i> Gene

“…The diagnosis of ELA syndrome was considered unlikely because these patients have combined manifestations of the three entities forming the acronym [Prontera et al, 2011], contrary to our family, where the son and his father each had a different TP63 phenotype. In addition, ELA syndrome has never been observed in more than one individual in the same family [Prontera et al, 2011;Otsuki et al, 2016Otsuki et al, , 2020.…”

“…However, some patients may have a phenotypic combination of two or more TP63 conditions, such as EEC3 and ADULT syndromes [Slavotinek et al, 2005;Reisler et al, 2006;Rinne et al, 2007;Kier-Swiatecka et al, 2007;van Zelst-Stams and van Steensel, 2009;Avitan-Hersh et al, 2010;Chacon-Camacho OF et al, 2016], or EEC3 andLMS [van Bokhoven et al, 2001]. In addition, patients whose phenotype overlaps with EEC3, LMS, and ADULT syndromes have been grouped under the acronym of ELA syndrome [Prontera et al, 2011;Otsuki et al, 2016Otsuki et al, , 2020. The genotype-phenotype correlation in these cases is not easy to explain, since an identical pathogenic variant may result in different TP63 phenotypes, with marked interfamilial variability, particularly with respect to the presence of ectrodactyly and CLP [Rinne et al, 2007;van Bokhoven et al, 2001].…”

Recent Advances in Syndactyly: Basis, Current Status and Future Perspectives

“…Furthermore, a heterozygous mutation in the NSDHL (c.713C>A;p.T238N) gene has been reported in a nine-month-old female affected with a CHILD syndrome phenotype and SD, who has non-consanguineous parents [64]. In addition, the TP63 gene has been found to be associated with SD in the presence of other abnormalities [65,66]. Recently, autosomal dominant SD has been associated with a microdeletion of 2.79 Mb at chr14q22-q22.2 in four affected members of a three-generation family with limb defects (syndactyly and polydactyly) along with other disorders, such as developmental delay and facial defects [67].…”