Cohen syndrome

Overview

Cohen syndrome is a rare, inherited genetic disorder that affects multiple systems in the body. It is characterized by developmental delay, intellectual disability, low muscle tone (hypotonia), distinctive facial features, retinal dystrophy (progressive vision loss), neutropenia (low levels of white blood cells), and a generally friendly personality. The condition is present from birth, but symptoms may become more apparent over time. Cohen syndrome varies in severity among individuals, even within the same family.

Causes

Cohen syndrome is caused by mutations in the VPS13B gene (also known as COH1), which is located on chromosome 8. This gene plays a role in intracellular protein transport and the structural integrity of various cells. Mutations in VPS13B impair cellular function, leading to the features seen in Cohen syndrome. The disorder is inherited in an autosomal recessive pattern, meaning a person must inherit two mutated copies of the gene (one from each parent) to be affected.

Symptoms

The signs and symptoms of Cohen syndrome vary but typically include a combination of physical, developmental, and hematologic features. Common symptoms include:

• Developmental delay: Delayed motor milestones and intellectual disability, often mild to moderate

• Hypotonia: Low muscle tone, particularly evident in infancy

• Distinctive facial features: Including thick hair and eyebrows, a short upturned nose, a prominent upper central incisors (teeth), and a down-slanting mouth

• Microcephaly: Small head circumference

• Retinal dystrophy: Progressive loss of vision due to retinal degeneration, often leading to night blindness and reduced peripheral vision

• Neutropenia: Low neutrophil count, which can increase the risk of infections

• Truncal obesity: Accumulation of body fat in the torso, with relatively thin limbs

• Joint hypermobility: Unusually flexible joints

• Speech and language delay: May include nasal-sounding speech

• Friendly disposition: A consistently cheerful and social personality is often noted

Diagnosis

Diagnosis of Cohen syndrome is based on clinical features and confirmed through genetic testing. Diagnostic steps include:

• Clinical evaluation: Based on characteristic physical traits, developmental delays, and vision problems

• Ophthalmologic examination: To identify signs of retinal dystrophy

• Complete blood count (CBC): To detect neutropenia

• Genetic testing: DNA analysis to identify mutations in the VPS13B gene

• Family history analysis: Helpful in assessing risk, especially in populations with known founder mutations (e.g., Finnish or Amish communities)

Treatment

There is no cure for Cohen syndrome, so treatment focuses on symptom management and supportive care. A multidisciplinary approach is recommended. Treatment strategies may include:

• Early intervention: Physical, occupational, and speech therapy to address developmental delays

• Educational support: Special education services tailored to cognitive needs

• Vision support: Regular ophthalmologic care and visual aids for retinal dystrophy

• Hematologic care: Monitoring and management of neutropenia, including antibiotics or G-CSF (granulocyte colony-stimulating factor) in severe cases

• Nutritional guidance: To manage truncal obesity and promote healthy growth

• Orthopedic care: For joint hypermobility or postural issues

• Genetic counseling: For families to understand inheritance patterns and recurrence risks

Prognosis

The prognosis for individuals with Cohen syndrome varies depending on the severity of symptoms. Many individuals live into adulthood and can lead fulfilling lives with appropriate support. Vision loss due to retinal dystrophy is often progressive and may lead to legal blindness in adolescence or adulthood. Neutropenia increases the risk of infections but is typically manageable. With early intervention, educational accommodations, and multidisciplinary care, quality of life and functional outcomes can be significantly improved.