Moynahan syndrome

Overview

Moynahan syndrome, also known as keratosis follicularis with multiple congenital anomalies, is an extremely rare genetic disorder characterized by a combination of skin abnormalities, intellectual disability, and multiple congenital malformations. First described by Moynahan in the 1970s, the syndrome is often considered a variant or an expanded phenotype of Darier disease, a known keratinization disorder. However, the presence of additional systemic features distinguishes Moynahan syndrome as a unique clinical entity.

Because of its rarity, only a limited number of cases have been documented in the medical literature. Affected individuals typically present with skin lesions similar to Darier disease, along with neurologic and developmental anomalies that can significantly impact quality of life and long-term outcomes.

Causes

The exact genetic cause of Moynahan syndrome is not fully understood, but it is believed to be related to mutations in the ATP2A2 gene, which encodes the sarco/endoplasmic reticulum Ca2+-ATPase type 2 (SERCA2). This gene is also implicated in classic Darier disease. The ATP2A2 protein plays a crucial role in calcium signaling within cells, especially in keratinocytes and neurons.

Genetic Characteristics

• Likely autosomal dominant inheritance: Though most cases are sporadic, some may be inherited in an autosomal dominant manner with variable expressivity.

• De novo mutations: Many cases appear to arise from spontaneous mutations in the absence of family history.

The broader systemic involvement in Moynahan syndrome, compared to typical Darier disease, suggests either a more severe mutation or the involvement of modifier genes that exacerbate the clinical phenotype.

Symptoms

Symptoms of Moynahan syndrome reflect a combination of cutaneous, neurological, and developmental abnormalities. These symptoms typically appear in infancy or early childhood and may become more apparent with age.

1. Skin Abnormalities

• Keratosis follicularis (wart-like papules, particularly in seborrheic areas)

• Hyperkeratotic plaques on the scalp, face, chest, and back

• Nail abnormalities (fragility, ridging, V-shaped notching)

• Mucosal lesions in the oral cavity (white papules or erosions)

2. Neurological and Cognitive Features

• Intellectual disability (mild to moderate)

• Delayed developmental milestones

• Seizures (reported in some cases)

• Speech delay or impaired language development

3. Congenital and Systemic Anomalies

• Craniofacial abnormalities (e.g., high-arched palate, dysmorphic facial features)

• Dental anomalies (malocclusion, crowded teeth)

• Musculoskeletal deformities (such as joint contractures or scoliosis in rare cases)

Symptoms can vary widely even among individuals with similar genetic changes, and severity ranges from mild skin involvement to profound developmental and systemic impairment.

Diagnosis

Diagnosis of Moynahan syndrome is primarily clinical, supported by dermatological findings and neurodevelopmental assessments. Genetic testing may be used to confirm a mutation in the ATP2A2 gene, but definitive diagnosis often depends on recognizing the distinct constellation of features.

Diagnostic Steps

• Clinical examination: Identification of characteristic skin lesions and neurologic abnormalities

• Skin biopsy: Shows suprabasal acantholysis and dyskeratosis, similar to Darier disease

• Neurodevelopmental assessment: Evaluation of cognitive, speech, and motor development

• Genetic testing: Sequencing of the ATP2A2 gene to identify pathogenic variants

Additional Investigations

• EEG in patients with seizures

• Neuroimaging (MRI) in cases with suspected structural brain anomalies

• Hearing and vision evaluations if developmental delays are present

Early diagnosis is important to initiate supportive care and anticipate potential complications, especially those related to intellectual development and seizure control.

Treatment

There is no cure for Moynahan syndrome. Treatment is supportive and focuses on managing skin symptoms, developmental delays, and any neurological complications. A multidisciplinary approach is essential, involving dermatologists, neurologists, developmental pediatricians, and therapists.

1. Dermatologic Management

• Topical retinoids: To reduce hyperkeratosis

• Topical corticosteroids or calcineurin inhibitors: For inflamed lesions

• Oral retinoids (e.g., acitretin): In severe or widespread cases (used with caution in children)

• Emollients and antiseptic washes to prevent secondary infections

2. Neurological and Developmental Support

• Speech and language therapy

• Occupational and physical therapy

• Antiepileptic medications for seizure control

• Special education and individualized learning plans

3. Monitoring and Supportive Care

• Regular follow-up with dermatology and neurology

• Dental care for malocclusion or oral lesions

• Psychosocial support for families

Early intervention can significantly improve developmental outcomes and quality of life in affected individuals.

Prognosis

The prognosis of Moynahan syndrome depends on the severity of neurological involvement and the effectiveness of symptom management. While the skin lesions can often be controlled with treatment, intellectual disability and developmental challenges may persist throughout life.

Favorable Factors

• Early diagnosis and initiation of therapy

• Access to comprehensive developmental and educational support

• Effective seizure control (if applicable)

Challenges

• Persistent intellectual and developmental impairments

• Psychosocial impact on family and caregivers

• Risk of secondary infections due to compromised skin barrier

With ongoing care and multidisciplinary support, individuals with Moynahan syndrome can achieve improved function and well-being. Long-term monitoring is essential to adapt treatment strategies and ensure the best possible outcomes.