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 genetic disorder that is inherited in an autosomal dominant pattern. It is 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) (1)


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. (1)



Individuals affected by the ADULT syndrome commonly display mutations in the P63 gene, particularly at the p.Arg337 (previously known as p.Arg298) residue within the DNA binding domain. The P63 gene, a p53 homolog, plays a crucial role in the development of normal skin and ectodermal structures as a transcription factor.



Diagnosis of the ADULT syndrome is typically made based on the evaluation of the characteristic clinical features, which may be apparent at birth or soon thereafter. To support the diagnosis and provide genetic counseling, genomic DNA analysis for a P63 gene mutation is recommended. Although there are several hallmark features associated with P63 mutation-related syndromes (as shown in Table 1), it should be noted that there can be substantial clinical overlap among these disorders. In approximately 30% of cases, a positive family history is present, while in the remaining 70%, the diagnosis is due to a de novo pathogenic variant. Reduced penetrance has also been reported in some cases. (1, 3)



The treatment and management of the ADULT syndrome necessitates interdisciplinary collaboration from various medical and surgical specialties. Surgical procedures may be utilized to partially correct limb deformities. Dental care is critical, as individuals may need multiple dentures throughout childhood and additional dental implants and bridges in adulthood. Topical emollients are used to address dry, eczematous areas of skin, and affected individuals typically require ophthalmological evaluation for lacrimal duct abnormalities.

Table 1 (1,4)

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    



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. Sutton VR, van Bokhoven H. TP63-Related Disorders. 2010 Jun 8 [updated 2021 Apr 1]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mirzaa G, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2021. PMID: 20556892.

2. 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.

3. 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.

4. 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.