SNP Shot: Genomic Insights

Costello syndrome is a multi-system disorder characterized by a range of features. These include developmental delays and intellectual disability, excess skin folds (particularly on the hands and feet), hypermobile joints, and distinct facial characteristics such as a large mouth with prominent lips. Cardiac issues are prevalent, encompassing arrhythmias, congenital heart defects, and hypertrophic cardiomyopathy, a condition where the heart muscle thickens and weakens. Infants may initially be larger at birth, but feeding difficulties and slower growth are typical. Individuals with Costello syndrome tend to have short stature and potentially reduced growth hormone. Further symptoms can involve tight Achilles tendons, hypotonia (low muscle tone), Chiari I malformation (a structural brain abnormality), skeletal and dental irregularities, and visual impairments.

Individuals with Costello syndrome have an elevated risk of developing both cancerous and non-cancerous tumors, starting in early childhood. Papillomas, benign wart-like growths usually around the nose, mouth, or anus, are the most common non-cancerous tumors. Rhabdomyosarcoma, a cancer originating in muscle tissue, is the most frequently associated cancerous tumor in childhood. Neuroblastoma, a tumor arising from developing nerve cells, has also been reported in children and adolescents with the syndrome. In addition, transitional cell carcinoma, a type of bladder cancer more common in older adults, has been observed in some teenagers with Costello syndrome.

The symptoms of Costello syndrome closely resemble those of cardiofaciocutaneous syndrome (CFC syndrome) and Noonan syndrome. Distinguishing between these three conditions in infancy based on physical features alone can be challenging. However, the underlying genetic causes and specific patterns of symptoms that emerge later in childhood allow for differentiation.

Inheritance:

Costello syndrome follows an autosomal dominant inheritance pattern, meaning that a single altered copy of the responsible gene is sufficient to cause the condition. Almost all cases arise from spontaneous, new gene mutations, occurring in individuals with no prior family history of the disorder.