Nicolaides-Baraitser syndrome

Nicolaides-Baraitser syndrome (NCBRS) is typically characterized by intellectual disability, seizures, short stature, sparse hair, distinctive facial features, short fingers and toes (brachydactyly), and prominent joints of the fingers and toes (called interphalangeal joints). Some features of the condition may vary among affected people.^[1]

All people with NCBRS have intellectual disability. In most cases it is severe, but in some cases it may be moderate or mild. Language is particularly limited, with at least 30% of affected people never developing speech. Major motor milestones such as sitting and walking are usually not very delayed. People with NCBRS are often happy and friendly, but may have temper tantrums or periods of aggression. Some people have some symptoms of autism spectrum disorder. Epilepsy occurs in about 2/3 of affected people. The type of seizures that occur can vary.^[1]

Facial characteristics are usually not recognized in younger affected people. They may include a triangular-shaped face; prominent eyelashes; a nose with a broad base, thick nostrils, and upturned tip; a broad philtrum; and wide mouth. The palpebral fissures (width of the eyes) are sometimes narrow and/or downslanting. As people with NCBRS age, the amount of subcutaneous fat tissue tends to decrease, making the skin below the eyes sagging and wrinkled, especially at the cheeks when smiling. However, some affected people retain full cheeks. Facial characteristics typically become more pronounced with increasing age. In some affected adults, the lower third of the face becomes markedly broad.^[1]

Sparse scalp hair is a major feature of NCBRS and is present in almost all affected people. It often gradually worsens with age, but in some people it improves over time. Skin is usually wrinkled and more noticeable in the distal limbs. Teeth may be widely spaced, and eruption of teeth (baby or adult) may be delayed. While the hands and feet usually appear normal at birth, the interphalangeal joints become prominent in the majority of affected people. Bone age can vary, and osteoporosis is not uncommon.^[1]

Nicolaides-Baraitser syndrome (NCBRS) is caused by mutations in the SMARCA2 gene, which is located on the small arm of chromosome 9. All mutations that have been identified in affected people have been either missense mutations or in-frame deletions.

There may be some correlations between specific types of mutations and some of the features that result (called genotype-phenotype correlations), but more studies are needed to draw definitive conclusions.^[1]

Nicolaides-Baraitser syndrome (NCBRS) is inherited in an autosomal dominant manner. This means that having a change (mutation) in only one of the two copies of the responsible gene in each cell is enough to cause features of the condition.

All known cases of NCBRS have been sporadic. This means it is thought that the mutation occurred for the first time in each affected person (called a de novo mutation). There have not been reports of NCBRS being inherited from a parent, or recurring in any family (with the exception of one pair of identical twins).^[1]

There is limited information about the life expectancy of people with Nicolaides-Baraitser syndrome (NCBRS) due to the rarity of the condition and the small number of reported cases in the literature. NCBRS was not recognized as a distinct condition until the 1990s, so there is limited information about older adults with NCBRS.

As of 2009, the first person reported with NCBRS was still living at age 32. Another person first reported in 1996 died at the age of 25 due to rupture of esophagus varices (the cause of which was not known). Also as of 2009, two French people, reported at ages 6 and 22 in 2003, were in excellent health without new physical problems and without progression of existing signs and symptoms.^[2]

While some features of NCBRS are always present, there is variability, and the severity of features may range from mild to severe.^[1] Therefore, the long-term outlook (prognosis) may vary among affected people.

Certain features of NCBRS can change or be progressive over time:^[1]

• Scalp hair is usually sparse at birth and usually becomes increasingly sparse with age, particularly in the second decade of life. However in some, the sparseness improves with time.^[3]
• Facial characteristics typically become more pronounced with increasing age. In some affected adults, the lower third of the face becomes markedly broad.^[1]
• As people with NCBRS age, the amount of subcutaneous fat tissue tends to decrease, making the skin below the eyes sagging and wrinkled, especially at the cheeks when smiling. However, some affected people retain full cheeks.^[1]
• The distal phalanges widen with age, becoming oval shaped and broad. Increasing space between the first and second toes can also occur over time.^[3]
• At first, finger mobility is normal (maybe even hypermobile). Later on mobility often decreases, and some older people dislike passive movements of their fingers.^[1]
• Osteoporosis is not uncommon and affected people may develop fractures in puberty or thereafter.^[1]
• Although psychomotor regression is not typical, the high incidence of seizures that progressively worsen has been associated with loss of speech.^[3]