Acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome is a rare autosomal dominant inherited disease caused due to mutations in the TP63 gene. More commonly, mutations in the TP63 gene result in ectodermal dysplasia and/or orofacial cleft. ADULT syndrome is a type of ectoderm-related tissue dysplasia. This case report describes a patient with chronic tearing, congenital atresia, and obstruction of the lacrimal ducts, which are the main clinical manifestations of ADULT syndrome. This patient also presented with some clinical manifestations that were different from those of ADULT syndrome, namely, mild eyelid fusion and abnormal development of the fifth finger (a stiff fifth finger with camptodactyly that was shortened in length). The gene mutation in this patient was also at a site different from those usually reported in the literature. In this patient, c.518G > T resulted in p. G173V (accession number: NM_003722; exon4). We performed successful dacryocystorhinostomy and artificial lacrimal duct implantation. As shown above, we discussed the clinical characteristics and genetics of the disease in detail. In sharing this case, we aim to contribute to the current understanding of the genes and clinical manifestations of ADULT syndrome and to assist clinicians in the clinical diagnosis of TP63 mutation-related diseases.

UNASSIGNED: Ectrodactyly is a rare congenital limb malformation characterized by a deep median cleft of the hand and/or foot due to the absence of central rays. It could be isolated or depicts a part of diverse syndromic forms. Heterozygous pathogenic variants in the TP63 gene are responsible for at least four rare syndromic human disorders associated with ectrodactyly. Among them, ADULT (Acro-Dermato-Ungual-Lacrimal-Tooth) syndrome is characterized by ectodermal dysplasia, excessive freckling, nail dysplasia, and lacrimal duct obstruction, in addition to ectrodactyly and/or syndactyly. Ophthalmic findings are very common in TP63-related disorders, consisting mainly of lacrimal duct hypoplasia. Absent meibomian glands have also been well documented in EEC3 (Ectrodactyly Ectodermal dysplasia Cleft lip/palate) syndrome but not in ADULT syndrome.
UNASSIGNED: We report a case of syndromic ectrodactyly consistent with ADULT syndrome, with an additional ophthalmic manifestation of agenesis of meibomian glands. The proband, as well as her elder sister, presented with congenital cone dystrophy.The molecular investigation was performed in the proband using Whole Exome Sequencing. Family segregation of the identified variants was confirmed by Sanger sequencing.
UNASSIGNED: Two clinically relevant variants were found in the proband: the novel de novo heterozygous missense c.931A > G (p.Ser311Gly) in the TP63 gene classified as pathogenic, and the homozygous nonsense pathogenic c.1810C > T (p.Arg604Ter) in the CNGB3 gene. The same homozygous CNGB3 variation was also found in the sister, explaining the cone dystrophy in both cases.
UNASSIGNED: Whole Exome Sequencing allowed dual molecular diagnoses: de novo TP63-related syndromic ectrodactyly and familial CNGB3-related congenital cone dystrophy.

Tumor protein p63 (TP63)-related disorders can be divided into at least six categories, including ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome 3 (EEC syndrome 3), ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (AEC syndrome), acro-dermo-ungual-lacrimal-tooth syndrome (ADULT syndrome), limb-mammary syndrome (LMS), Rapp-Hodgkin syndrome (RHS) and split-hand/foot malformation 4 (SHFM4), and are all a result of heterozygous mutations of TP63. The phenotypes of TP63-related disorders broadly involve ectodermal dysplasias, acromelic malformation and orofacial cleft. SHFM and hypodontia are prominent clinical manifestations of TP63-related disorders.
The present study investigated a family with SHFM and hypodontia; determined the sequences of DLX5, WNT8B, WNT10B, BHLHA9, CDH3, DYNC1I1 and FGFR1; and performed single nucleotide polymorphism-array analysis. We detected the mutation by multiple sequence alignments and a bioinformatic prediction.
We identified a novel missense mutation of TP63 (c.1010G>T; R337L) in the family without mutations of DLX5, WNT8B, WNT10B, BHLHA9, CDH3, DYNC1I1, FGFR1 and copy number variants causing SHFM.
A mutation of TP63 (c.1010G>T; R337L) leads to SHFM with hypodontia. The identification of this mutation expands the spectrum of known TP63 mutations and also may contribute to novel approaches for the genetic diagnosis and counseling of families with TP63-related disorders.

The TP63 gene has been described in 5 overlapping limb malformation disorders, including a rare autosomal dominant ectodermal disorder named acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome. This article describes 2 patients with ectrodactyly and variable features related to ectodermal dysplasia/ADULT syndrome, and the polymorphism rs16864880 in the TP63 gene, which was not present in their parents. The role of this variant in the genesis of this condition is discussed, based upon a review of 40 cases. The results suggested that rs16864880 may not be directly related to ADULT syndrome. However, it is not possible to exclude its participation in gene interactions in the limb development pathway.