Hay–Wells syndrome

Overview

Hay–Wells syndrome, also known as AEC syndrome (Ankyloblepharon-Ectodermal defects-Cleft lip/palate), is a rare genetic disorder that affects the development of the skin, hair, nails, teeth, and sweat glands. It is part of a larger group of disorders called ectodermal dysplasias. First described by Hay and Wells in 1976, the condition is characterized by a triad of features: fusion of the eyelids at birth (ankyloblepharon), ectodermal dysplasia (affecting structures derived from the ectoderm), and cleft lip and/or palate. The severity and combination of symptoms can vary widely between individuals.

Causes

Hay–Wells syndrome is caused by mutations in the TP63 gene, which plays a critical role in the development and maintenance of epithelial tissues. This gene provides instructions for making a protein that is essential for the proper development of skin, limbs, and facial structures. The condition follows an autosomal dominant inheritance pattern, meaning only one copy of the altered gene is sufficient to cause the disorder. In some cases, the mutation may arise spontaneously (de novo) without a family history.

Symptoms

The symptoms of Hay–Wells syndrome vary, but the most common features include:

• Ankyloblepharon: Partial or complete fusion of the eyelids at birth

• Cleft lip and/or palate: A gap or split in the upper lip and/or roof of the mouth

• Ectodermal dysplasia:

  • Sparse, wiry, or absent scalp hair

  • Abnormal or missing teeth (conical or peg-shaped)

  • Thin, brittle nails or nail dysplasia

  • Reduced or absent sweating (hypohidrosis)

  • Dry, scaly skin

• Chronic skin erosions, especially on the scalp

• Hearing problems in some individuals

The combination of these symptoms can significantly affect physical appearance and quality of life.

Diagnosis

Diagnosis of Hay–Wells syndrome is based on clinical evaluation, family history, and genetic testing. Key diagnostic steps include:

• Physical examination: Identification of characteristic features such as ankyloblepharon, ectodermal abnormalities, and facial clefts

• Genetic testing: Detection of mutations in the TP63 gene

• Family history: Assessment of inheritance pattern

• Specialist evaluations: ENT, dermatology, ophthalmology, and dental assessments as needed

Early diagnosis is important for planning multidisciplinary care and surgical interventions.

Treatment

Treatment for Hay–Wells syndrome is supportive and symptom-specific, involving a team of specialists to manage the various manifestations:

• Surgical correction: Repair of cleft lip/palate and separation of fused eyelids

• Dermatologic care: Treatment for chronic scalp erosions and dry skin with emollients, antibiotics, or wound care

• Dental care: Management of abnormal teeth and planning for prosthetic devices if needed

• Hearing aids: If hearing loss is present

• Cooling strategies: For patients with reduced sweating to prevent overheating

• Speech therapy: For children with cleft palate or associated delays

Psychological support and genetic counseling are also recommended for affected individuals and their families.

Prognosis

The prognosis for individuals with Hay–Wells syndrome depends on the severity of symptoms and access to medical care. While the condition is lifelong, many complications can be managed effectively with appropriate interventions. With coordinated care, most individuals can lead fulfilling lives. However, recurrent infections, feeding issues, and cosmetic concerns may pose ongoing challenges, particularly in early childhood. Regular follow-up with a multidisciplinary team is essential for optimal outcomes.