SNP Shot: Genomic Insights

Nicolaides-Baraitser syndrome is a complex disorder impacting various body systems. Individuals affected by this condition can exhibit a wide range of symptoms, the most common of which include sparse scalp hair, a smaller than normal head size (microcephaly), distinctive facial features, short stature, prominent finger joints, unusually short fingers and toes (brachydactyly), recurring seizures (epilepsy), and intellectual disability ranging from moderate to severe, along with impaired language skills.

Sparse scalp hair is often one of the first noticeable signs of Nicolaides-Baraitser syndrome, typically appearing in infancy. While the hair present typically has a normal growth rate and texture, the overall amount tends to decrease over time. Many affected adults have very little hair. However, in rare instances, the scalp hair may increase with age. Eyebrows may become thinner as individuals age, but the eyelashes generally remain normal. At birth, there might be excessive facial hair (hypertrichosis), which tends to thin out as the child grows.

Growth delays are common in individuals with this syndrome, resulting in short stature and microcephaly. In some cases, growth may be unusually slow even before birth.

People with Nicolaides-Baraitser syndrome often share characteristic facial features, including a triangular face shape, deep-set eyes, a thin nasal bridge, wide nostrils, a pointed nasal tip, and a thick lower lip. The face may also exhibit a lack of subcutaneous fat, leading to premature wrinkling. The lack of subcutaneous fat may also cause the skin to appear pale, with visible veins.

The absence of subcutaneous fat in the hands makes the finger joints appear larger than normal in individuals with Nicolaides-Baraitser syndrome. Over time, the fingertips tend to become broad and oval-shaped. A wide gap between the first and second toes (sandal gap) is also typically present.

Epilepsy is common in people with Nicolaides-Baraitser syndrome, often starting in infancy. Affected individuals may experience various types of seizures, which can be difficult to control with medication.

Almost all individuals with Nicolaides-Baraitser syndrome have moderate to severe intellectual disability. While early developmental milestones like crawling and walking may be achieved at a normal age, further development is often limited, and language development is significantly impaired. About one-third of affected individuals never develop the ability to speak, while others may lose their verbal communication skills over time. Despite these challenges, individuals with this condition are often described as having a happy disposition and being very friendly, although they may also experience periods of aggression or temper tantrums.

Other signs and symptoms associated with Nicolaides-Baraitser syndrome include eczema, an inflammatory skin condition. Approximately half of affected individuals have a soft bulge around the belly button (umbilical hernia) or in the lower abdomen (inguinal hernia). Some individuals may also have dental problems, such as widely spaced teeth, delayed tooth eruption, or missing teeth (hypodontia). Most affected males have undescended testes (cryptorchidism), and females may have underdeveloped breasts. Feeding problems are also reported in nearly half of individuals with Nicolaides-Baraitser syndrome.

Inheritance:

Nicolaides-Baraitser syndrome is inherited in an autosomal dominant manner. This means that only one copy of the altered gene in each cell is sufficient to cause the disorder. In nearly all cases, the condition results from new (de novo) mutations in the gene. These mutations occur either during the formation of egg or sperm cells or in early embryonic development. Consequently, affected individuals typically have no family history of the disorder.