Disease group Ectodermal Dysplasia
Synonymous Acro-dermato-ungual-lacrimal-tooth syndrome
Estimated prevalence -
OMIM 103285
Inheritance Autosomal Dominant
Gene (s) p63 (603273)


ADULT syndrome is a rare autosomal dominant disorder characterized by ectrodactyly (congenital abnormality involving the absence of some fingers or toes), excessive freckling, nail dystrophy, lacrimal duct abnormalities, hypoplastic breasts/nipples and hypodontia. An association with p63 gene mutations was first described by Duijf et al in 2002. Mutations in this transcription factor have also been identified in other ectodermal dysplasia syndromes including AEC (ankyloblepharon-ectodermal dysplasia-clefting; Hay Wells; OMIM 106260) syndrome, EEC (ectrodactyly, ectodermal dysplasia, cleftting; OMIM 129900) limb-mammary syndrome (OMIM 603543), split-hand split-foot malformation syndrome (OMIM 605289) and, most recently, Rapp-Hodgkin syndrome (OMIM 129400). (see table below)

Clinical Description

Infants are born with ectrodactyly (split-hand/foot malformation) and variable ectodermal dysplasia features. Individuals commonly have widespread dry, atrophic and eczematous skin as well as nail dystrophy. Dental anomalies (malformed teeth (conical shape) and hypodontia (reduced number of teeth) commonly develop during childhood and adolescence. Hair (as well as eye brows and eye lashes) is typically light-colored and may be sparse, coarse, wiry and difficult to comb. These changes become more obvious with age. Heat intolerance due to subjective decreased sweat production has been reported. Excessive freckling in sun exposed areas may be present as well as lacrimal duct atresia (causing chronic conjunctivitis and blepharitis) and breast/nipple hypoplasia. Most common limb anomalies include syndactyly of fingers and toes.


Many affected individuals show mutations within the p63 gene, with a hotspot mutation occurring within the DNA binding domain of the gene at p.Arg337 (formerly known as p.Arg298) residue. The p63 gene is a p53 homolog, and is an important transcription factor in the development of normal skin and ectodermal structures.


Diagnosis is usually made by assessment of the clinical features either at, or soon after birth. Genomic DNA should be analysed for a p63 gene mutation in order to help confirm the diagnosis and assist with genetic counselling. Classically, there are several distinguishing features of syndromes associated with p63 mutation (Table 1), practically, however, considerable clinical overlap occurs (ref 1). A positive family history is present in 30%, whereas in 70% a de novo pathogenic variant is causative. Reduced penetrance has been reported (ref 2)


The management of the ADULT syndrome requires expertise from various medical and surgical specialties. Limb deformities may be partially corrected by surgical procedures. Dental treatment is extremely important as many require successive dentures as a child with addition of dental implants and bridges later in adult life. Topical emollients are required to treat dry, eczematous areas of skin and many affected individuals require ophthalmological review regarding lacrimal duct abnormalities.

Table 1 (ref 3)

  TP63-Related Disorder
Feature AEC ADULT EEC3 Limb-
SHFM4 Isolated
Inheritance AD AD AD AD AD AD
Ankyloblepharon filiforme adnatum X          
Ectodermal dysplasia: X X X Rare    
  • Hypohidrosis (mostly subjective)**
X X X      
  • Nail dysplasia
X X Mid X    
  • Sparse hair
X X X      
  • Tooth abnormalities
X X X X    
Cleft lip/palate X X X X    
Split-hand/foot malformation/syndactyly X X X X X  
Lacrimal duct obstruction X X X X    
Dermal erosions X          
Hypopigmentation X X X      
Hypospadias X X        
Trismus (“lockjaw”) X          
Excessive freckling X          
Hypoplastic breasts X X        
Hypoplastic nipples X X        


AD = autosomal dominant; ADULT = acro-dermato-ungual-lacrimal-tooth; AEC = Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome; CL/P = cleft lip/cleft palate; EEC = ectrodactyly (split-hand/foot malformation), ectodermal dysplasia, clefting; SHFM4 = split-hand/foot malformation type 4

* strands of tissue that completely or partially fuse the upper and lower eyelids

** starch iodide sweat testing of the palms is rarely helpful in documenting sweating ability


1. Otsuki Y, Ueda K, Satoh C, Maekawa R, Yoshiura KI, Iseki S. Intermediate Phenotype between ADULT Syndrome and EEC Syndrome Caused by R243Q Mutation in TP63. Plast Reconstr Surg Glob Open. 2016;4(12):e1185.

2. Amiel J, Bougeard G, Francannet C, Raclin V, Munnich A, Lyonnet S, et al. TP63 gene mutation in ADULT syndrome. Eur J Hum Genet. 2001;9(8):642-645.

3. Sutton VR, van Bokhoven H. TP63-Related Disorders (last revision 12/2019). In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, et al., editors. GeneReviews(®). Seattle (WA): University of Washington, Seattle; 1993.