SNP Shot: Genomic Insights

Cornelia de Lange syndrome (CdLS) is a developmental condition that affects various bodily systems. The symptoms and severity of CdLS differ greatly among individuals, ranging from mild to profound.

Hallmarks of CdLS include slow growth, both before and after birth, resulting in short stature; typically moderate to severe intellectual disability; and bone abnormalities affecting the arms, hands, and fingers. Most individuals with CdLS possess characteristic facial features such as arched eyebrows that often merge (synophrys), long eyelashes, low-positioned ears, small and spaced-out teeth, and a small, upturned nose. Many also exhibit traits similar to those found in autism spectrum disorder, impacting communication and social skills.

Other potential signs and symptoms of CdLS include excessive hair growth (hypertrichosis), an abnormally small head size (microcephaly), hearing impairment, and digestive issues. Some individuals are born with a cleft palate, an opening in the roof of the mouth. Seizures, cardiac defects, and vision problems have also been observed in individuals with CdLS.

Inheritance:

CdLS caused by variations in the NIPBL, RAD21, or SMC3 genes follows an autosomal dominant inheritance pattern. This means that only one copy of the mutated gene in each cell is enough to cause the disorder. In the majority of cases, the condition arises from spontaneous new gene mutations in individuals without a family history of CdLS. When CdLS is caused by variations in the HDAC8 or SMC1A gene, the condition has an X-linked dominant inheritance pattern. An X-linked condition occurs when the responsible mutated gene resides on the X chromosome. Research suggests that only one copy of the altered HDAC8 or SMC1A gene is enough to cause X-linked CdLS. Females, with two X chromosomes, may experience milder symptoms compared to affected males, who possess only one X chromosome. Most X-linked CdLS cases stem from new mutations in the HDAC8 or SMC1A gene, occurring in individuals without a prior family history of the condition.