SNP Shot: Genomic Insights

KCNK9 imprinting syndrome is a rare disorder present from birth, primarily marked by reduced muscle tone (hypotonia). This leads to lethargy, a feeble cry, and decreased movement in affected infants. Feeding challenges arise from facial weakness and a weak suck, often resulting in failure to thrive, meaning difficulty gaining weight and growing properly. Swallowing problems (dysphagia) often persist into adolescence. While muscle tone can improve, some degree of weakness typically continues into adulthood. This weakness may contribute to permanently bent joints (contractures) and spinal curvature (scoliosis).

Intellectual disability and delays in developmental milestones like speech and motor skills (sitting, walking) are also characteristic of KCNK9 imprinting syndrome. Many individuals affected have limited speech capabilities throughout their lives.

Distinctive facial features are associated with this condition, including a long face that narrows toward the temples, an upward-pointing upper lip (tented lip), a short and wide space between the nose and lip (philtrum), a small lower jaw (micrognathia), and unusually shaped eyebrows. Some individuals may also have a cleft palate. Other physical characteristics can include a long neck, a narrow chest, and tapered fingers.

Inheritance:

KCNK9 imprinting syndrome is inherited in an autosomal dominant manner, meaning that only one altered copy of the gene in each cell is enough to cause the condition. Humans inherit one copy of each gene from each parent. Normally, both gene copies are active. However, KCNK9 is subject to genomic imprinting, meaning only one parental copy is active. Specifically, KCNK9 is a maternally expressed imprinted gene, so only the mother's copy is active, while the father's copy is silenced (turned off). Typically, the altered gene is inherited from the mother. Since the father's copy is silenced, he cannot pass the condition on to his children. Approximately 20% of cases arise from new gene mutations in individuals with no prior family history of the disorder.