Nicolaides–Baraitser syndrome

Overview

Nicolaides–Baraitser syndrome (NCBRS) is a rare genetic disorder characterized by distinctive facial features, sparse hair, intellectual disability, epilepsy, and skeletal abnormalities. First described in the early 1990s by pediatricians Paola Nicolaides and Michael Baraitser, the syndrome has since been identified in a growing number of individuals thanks to advances in genetic testing.

The syndrome presents with a combination of physical, neurological, and developmental features. Symptoms are often noticeable in infancy or early childhood, and while the severity varies, most affected individuals experience significant developmental delay and require lifelong care.

Causes

Nicolaides–Baraitser syndrome is caused by mutations in the SMARCA2 gene, which encodes a protein that plays a critical role in the regulation of gene expression and chromatin remodeling. The SMARCA2 gene is part of the SWI/SNF complex, which helps regulate access to DNA for processes like transcription and replication.

The condition is typically the result of a de novo mutation, meaning it occurs spontaneously and is not inherited from either parent. However, it follows an autosomal dominant inheritance pattern, so there is a 50% chance of transmission if an affected individual has children.

Symptoms

Symptoms of NCBRS often become more pronounced with age. They involve multiple systems, including the central nervous system, facial development, hair growth, and the musculoskeletal system.

Facial and Craniofacial Features

• Coarse facial features

• Wide nasal bridge and prominent eyebrows

• Thin upper lip and thick lower lip

• Large mouth with widely spaced teeth

• Prominent philtrum (vertical groove between the nose and upper lip)

• Microcephaly (small head size)

Hair and Skin Features

• Sparse scalp hair, eyebrows, and eyelashes

• Dry, rough skin

Neurological and Cognitive Features

• Moderate to severe intellectual disability

• Global developmental delay (motor and speech milestones)

• Seizures or epilepsy (often drug-resistant)

• Hypotonia (reduced muscle tone) in infancy

• Autistic behaviors or sensory processing issues

Skeletal and Growth Features

• Short stature

• Broad thumbs and toes

• Joint stiffness or hypermobility

• Delayed bone age and skeletal dysplasia

Other Possible Features

• Feeding difficulties in infancy

• Constipation and gastrointestinal issues

• Hearing loss (in some cases)

Diagnosis

Diagnosing Nicolaides–Baraitser syndrome requires a combination of clinical evaluation and genetic testing. Due to its rarity and overlap with other developmental syndromes, it may not be immediately recognized.

Diagnostic Process

• Clinical examination: Identification of characteristic facial features, developmental delay, and limb anomalies

• Developmental assessment: Evaluation of cognitive and motor delays

• EEG: To assess for epileptic activity in patients with seizures

• MRI: Brain imaging may show structural abnormalities or cortical atrophy

• Genetic testing: Identification of a pathogenic mutation in the SMARCA2 gene confirms the diagnosis

Treatment

There is no cure for Nicolaides–Baraitser syndrome, and treatment is supportive and tailored to the individual’s symptoms and developmental needs. A multidisciplinary care team is essential and may include neurologists, developmental pediatricians, speech and occupational therapists, and orthopedic specialists.

Management Strategies

• Seizure control: Antiepileptic drugs (AEDs), although some seizures may be refractory to treatment

• Speech therapy: For expressive and receptive language delay

• Occupational and physical therapy: To improve motor skills and muscle tone

• Behavioral therapy: To manage sensory issues and social interaction difficulties

• Educational support: Special education programs tailored to cognitive abilities

• Nutritional support: Feeding therapy or gastrostomy tube in cases of severe feeding issues

Monitoring and Supportive Care

• Regular neurologic evaluations for seizure management

• Orthopedic evaluations for joint and skeletal issues

• Routine developmental and behavioral assessments

• Hearing and vision screenings

Prognosis

The prognosis for Nicolaides–Baraitser syndrome varies depending on the severity of symptoms, especially intellectual disability and seizure control. Most individuals have moderate to severe developmental delay and require lifelong support. Seizures may be difficult to manage and can impact quality of life.

Although life expectancy is not well defined due to the rarity of the syndrome, many individuals survive into adulthood with appropriate care and management. Early diagnosis, intervention, and consistent medical follow-up are essential to improving outcomes and enhancing functional abilities.

Ongoing research and case documentation are crucial for better understanding of this complex syndrome and for the development of future therapeutic strategies.