De Barsy syndrome

Overview

De Barsy syndrome is a rare genetic disorder characterized primarily by premature aging (progeroid appearance), distinctive facial features, intellectual disability, growth delays, and skin abnormalities. It is classified as a cutis laxa disorder, which means it involves loose, sagging, and wrinkled skin due to connective tissue defects. First described by De Barsy in 1967, the condition affects multiple body systems and varies significantly in severity among affected individuals.

Causes

De Barsy syndrome results from genetic mutations affecting connective tissue structure and function. It is primarily inherited in an autosomal recessive manner, meaning two copies of the defective gene—one from each parent—must be inherited. Known genetic mutations associated with De Barsy syndrome include those in the ALDH18A1 and PYCR1 genes. These genes are essential for producing enzymes involved in the metabolism of proline, an amino acid critical for collagen production and connective tissue stability.

Symptoms

Symptoms of De Barsy syndrome manifest at or shortly after birth, typically affecting skin, neurological development, and facial appearance. Common signs and symptoms include:

• Skin abnormalities: Loose, sagging skin (cutis laxa), thin and translucent appearance, premature wrinkles, and diminished subcutaneous fat.

• Facial characteristics: Distinctive progeroid facial features including large ears, prominent forehead, widely spaced eyes (hypertelorism), thin lips, and small chin.

• Growth delays: Short stature, low weight, and delayed physical development.

• Neurological issues: Intellectual disability, developmental delays, hypotonia (low muscle tone), seizures, and impaired coordination.

• Eye abnormalities: Corneal clouding, cataracts, or nearsightedness (myopia).

• Skeletal abnormalities: Joint laxity or stiffness, scoliosis, or hip dislocation.

Diagnosis

Diagnosing De Barsy syndrome typically involves clinical assessment supported by genetic testing. Steps include:

• Physical examination: Observing characteristic skin features, facial appearance, and growth patterns.

• Detailed medical history: Assessing developmental milestones, family medical background, and symptom progression.

• Genetic testing: Molecular analysis such as whole-exome sequencing to identify mutations in genes including ALDH18A1 and PYCR1.

• Imaging studies: X-rays or MRI may be used to evaluate skeletal anomalies or neurological development.

• Ophthalmologic evaluation: Examination by an eye specialist to detect and monitor eye-related complications.

Treatment

No cure currently exists for De Barsy syndrome, and treatment is supportive, aimed at symptom management and improving quality of life. Treatment strategies typically involve a multidisciplinary team approach and include:

• Dermatologic management: Regular skin care, moisturizers, and careful monitoring to prevent complications.

• Neurological support: Antiepileptic medications for seizures, early developmental intervention programs, and physical and occupational therapy to enhance motor and cognitive function.

• Orthopedic interventions: Physiotherapy and orthopedic support to address joint issues, scoliosis, or hip abnormalities.

• Ophthalmologic care: Regular vision screenings and treatments for cataracts or corneal clouding, potentially involving surgical intervention.

• Nutritional support: Specialized dietary plans and nutritional supplements to address growth and feeding difficulties.

• Genetic counseling: Essential for families to understand inheritance patterns, recurrence risks, and family planning options.

Prognosis

The prognosis for individuals with De Barsy syndrome varies widely based on symptom severity, presence of complications, and quality of supportive care. Severe cases can experience significant neurological and developmental impairments, potentially leading to a shortened lifespan. With appropriate multidisciplinary management and early therapeutic interventions, many affected individuals can achieve improved health outcomes, enhanced comfort, and better quality of life despite the chronic nature of the syndrome.