Acro–dermato–ungual–lacrimal–tooth syndrome

Overview

Acro–dermato–ungual–lacrimal–tooth (ADULT) syndrome is a rare genetic disorder that affects the development of the skin, limbs, nails, eyes, and teeth. It is considered part of the group of disorders known as ectodermal dysplasias, which involve abnormalities in tissues derived from the ectoderm layer during embryonic development. ADULT syndrome presents at birth or in early childhood and is characterized by a wide range of symptoms, including limb malformations, dental anomalies, nail dysplasia, skin issues, and tear duct defects.

Causes

ADULT syndrome is caused by mutations in the TP63 gene. This gene provides instructions for making a protein that plays a key role in the development of ectodermal structures, such as the skin, limbs, nails, teeth, and glands. The condition follows an autosomal dominant inheritance pattern, which means only one copy of the altered gene is sufficient to cause the syndrome. Most cases are inherited from an affected parent, but some may result from new (de novo) mutations.

Symptoms

ADULT syndrome affects multiple systems. While symptoms vary between individuals, common features include:

Acro (Limb) Abnormalities:

• Split or missing fingers or toes (ectrodactyly or lobster-claw deformity)

• Webbing (syndactyly) or shortened digits

Dermato (Skin) Abnormalities:

• Dry, scaly, or thin skin

• Hyperkeratosis (thickening of the skin) on palms and soles

Ungual (Nail) Abnormalities:

• Small, ridged, discolored, or absent fingernails and toenails

Lacrimal (Tear Duct) Anomalies:

• Underdeveloped or absent tear ducts

• Dry eyes or frequent eye infections

Tooth Abnormalities:

• Missing teeth (hypodontia)

• Abnormally shaped or widely spaced teeth

• Delayed tooth eruption

Some individuals may also have sparse hair, underdeveloped sweat glands, or genital anomalies (more commonly reported in males).

Diagnosis

Diagnosis of ADULT syndrome is based on clinical features and confirmed through genetic testing. Key diagnostic steps include:

• Physical examination: To evaluate limb, nail, skin, dental, and facial features

• Dental and dermatological assessments: To document missing or malformed teeth and skin abnormalities

• Ophthalmologic exam: To assess tear duct structure and function

• Genetic testing: Identification of mutations in the TP63 gene confirms the diagnosis

• Family history: To determine inheritance pattern

Treatment

There is no cure for ADULT syndrome, but symptoms can be managed through a multidisciplinary approach involving dermatologists, dentists, ophthalmologists, orthopedic specialists, and genetic counselors. Treatment options include:

• Dental prosthetics or implants: To replace missing teeth and improve function and appearance

• Moisturizers and skin care: For dry or scaly skin

• Artificial tears or tear duct procedures: To manage dry eyes

• Reconstructive or corrective limb surgery: For functional improvement in hand or foot anomalies

• Nail and hair care: Supportive treatments for cosmetic and protective purposes

• Genetic counseling: For affected individuals and families

Prognosis

The prognosis for individuals with ADULT syndrome is generally favorable. While the condition involves multiple physical abnormalities, it does not typically affect life expectancy or intelligence. Most individuals can lead full lives with supportive care and treatment. Early diagnosis and intervention improve both functional outcomes and quality of life, particularly in managing dental, ocular, and limb-related challenges.