EEM syndrome

Overview

EEM syndrome—short for Ectodermal dysplasia, Ectrodactyly, and Macular dystrophy syndrome—is a very rare inherited disorder that affects multiple body systems. The condition combines abnormalities of the skin, hair, teeth, and nails (ectodermal dysplasia), limb malformations such as split hand/foot (ectrodactyly), and progressive vision loss due to macular dystrophy, which affects the central part of the retina. EEM syndrome shares some clinical features with other syndromes involving ectodermal dysplasia and limb anomalies, such as EEC syndrome, but its inclusion of retinal involvement makes it distinct.

Causes

EEM syndrome is caused by mutations in the CDH3 gene, which encodes P-cadherin, a protein essential for cell-to-cell adhesion in epithelial tissues and the retina. The syndrome is inherited in an autosomal recessive pattern, meaning an individual must inherit two copies of the mutated gene—one from each parent—to be affected. Carriers typically show no symptoms. The condition is extremely rare, with very few families reported worldwide.

Symptoms

The symptoms of EEM syndrome vary among individuals but typically involve three major systems:

1. Ectodermal dysplasia:

• Sparse, brittle hair (hypotrichosis)

• Abnormal or missing teeth (hypodontia)

• Nail dystrophy (abnormal nail growth or shape)

• Dry, thin, or scaly skin

2. Ectrodactyly:

• Split hand/foot malformations (also called "lobster-claw" deformities)

• Missing or fused fingers and toes

• Asymmetrical limb development

3. Macular dystrophy:

• Progressive central vision loss

• Onset often begins in childhood or adolescence

• Macular changes visible on retinal imaging

• Peripheral vision is typically preserved

Other possible features may include mild facial differences, hearing loss, or palmoplantar keratoderma (thickened skin on the palms and soles), though these are less common.

Diagnosis

Diagnosis of EEM syndrome is based on clinical features, family history, and confirmed through genetic testing. Diagnostic steps include:

• Physical examination: Identification of limb anomalies, dental issues, and ectodermal signs

• Ophthalmologic evaluation: Fundoscopy and retinal imaging to assess macular dystrophy

• Dental and dermatological evaluation: For assessment of missing teeth, hair, and nail changes

• Genetic testing: Sequencing of the CDH3 gene to confirm the diagnosis

• Family history analysis: Helps identify inheritance patterns and assess carrier status in relatives

Treatment

There is no cure for EEM syndrome, and treatment focuses on managing individual symptoms and improving quality of life. A multidisciplinary team approach is typically required. Management may include:

• Ophthalmologic care: Regular eye exams and low-vision aids as vision deteriorates

• Dentistry: Dental prostheses or implants to manage missing or malformed teeth

• Orthopedic and reconstructive surgery: For correction or improvement of limb malformations

• Dermatologic care: Moisturizers and treatments for dry skin or nail abnormalities

• Genetic counseling: For affected families planning for children

• Psychosocial support: To address emotional and social challenges related to visible differences or vision loss

Prognosis

The prognosis for individuals with EEM syndrome depends on the severity of the symptoms and access to medical care. While limb malformations and dental issues can be surgically or prosthetically managed, the progressive vision loss associated with macular dystrophy can have a significant impact on independence and quality of life. With proper support, individuals with EEM syndrome can lead meaningful lives, though lifelong medical care and adaptive strategies are often necessary.