Lelis syndrome

Overview

Lelis syndrome, also known as ectodermal dysplasia with acanthosis nigricans, is an extremely rare genetic disorder characterized by abnormalities in the development of ectodermal structures—primarily the skin, hair, nails, and teeth—combined with acanthosis nigricans, a skin condition marked by dark, velvety patches in body folds. The condition is typically present from birth or early infancy and affects multiple body systems. Lelis syndrome was first described in 1981 and remains poorly understood due to the limited number of reported cases.

Causes

Lelis syndrome is believed to be caused by an inherited genetic mutation that affects ectodermal development and skin pigmentation. The exact gene responsible for the syndrome has not yet been definitively identified. Most reported cases suggest an autosomal recessive inheritance pattern, meaning a child must inherit two copies of the defective gene—one from each parent—to manifest the condition. Consanguinity (marriage between close relatives) has been noted in some families with affected individuals, supporting this inheritance pattern.

Symptoms

Lelis syndrome presents with a combination of features typical of ectodermal dysplasia and acanthosis nigricans. Common signs and symptoms include:

• Acanthosis nigricans – dark, thickened, velvety skin in body folds such as the neck, armpits, and groin

• Hypotrichosis – sparse or absent scalp hair, eyebrows, and eyelashes

• Hypohidrosis or anhidrosis – reduced or absent sweating, leading to overheating

• Dental anomalies – including missing teeth (hypodontia), malformed teeth, or delayed eruption

• Nail abnormalities – thick, brittle, or misshapen nails

• Dry or scaly skin – with possible thickening (hyperkeratosis)

In some cases, additional features such as developmental delays or metabolic disturbances may be observed, although these are not consistently present in all cases.

Diagnosis

Diagnosis of Lelis syndrome is based on the combination of clinical findings related to ectodermal dysplasia and the presence of acanthosis nigricans. Steps in the diagnostic process may include:

• Clinical examination – assessment of hair, skin, teeth, and nails for characteristic abnormalities

• Skin biopsy – may show thickened epidermis with pigmentation typical of acanthosis nigricans

• Family history analysis – to assess for hereditary patterns and consanguinity

• Genetic testing – although no specific gene has been pinpointed, broad genetic panels for ectodermal dysplasias may help in some cases

Due to its rarity and overlap with other ectodermal syndromes, Lelis syndrome can be challenging to diagnose without a multidisciplinary evaluation.

Treatment

There is no cure for Lelis syndrome, and treatment is symptomatic, focusing on improving quality of life and managing individual symptoms. Common therapeutic approaches include:

• Dermatologic care – use of moisturizers, keratolytic agents, and topical treatments for acanthosis nigricans

• Dental care – including prosthetics or orthodontic correction for missing or malformed teeth

• Cooling measures – to manage overheating due to impaired sweating (e.g., cooling vests, air-conditioned environments)

• Hair and nail management – cosmetic or protective treatments as needed

• Psychological support – for coping with visible differences and social challenges

Prognosis

The long-term outlook for individuals with Lelis syndrome depends on the severity of symptoms and access to multidisciplinary care. While the condition is chronic and can impact appearance and comfort, it is not typically life-threatening. With appropriate medical, dental, and supportive treatment, many individuals can lead relatively normal lives. Early diagnosis and ongoing management can significantly improve quality of life and help address both physical and psychosocial aspects of the syndrome.