A Novel Missense Mutation of the ABL1 Gene in a Child With Congenital Heart Defects and Skeletal Malformations Syndrome

Abstract

Congenital heart defects and skeletal malformations syndrome (CHDSKM) is a rare autosomal dominant genetic disorder characterized by specific clinical features, including dysmorphic facial traits, congenital heart defects, skeletal abnormalities, joint issues, and failure to thrive. The novelty of this case lies in the identification of a novel mutation in the ABL1 gene, expanding the genetic spectrum associated with this syndrome. A 5.9-year-old boy was referred to the clinic due to growth retardation and intellectual disability. Clinical evaluation revealed several hallmark features of CHDSKM, including distinct facial dysmorphisms such as a broad forehead, frontal bossing, micrognathia, low-set ears, and short palpebral fissures. The patient was diagnosed with congenital heart defects, including a ventricular septal defect, atrial septal defect, and patent ductus arteriosus. Skeletal malformations included scoliosis and finger contractures. Additionally, he exhibited developmental delay, gastrointestinal issues such as umbilical hernia and intestinal malrotation, intellectual disability, and dysgenesis of the corpus callosum, which are atypical for this syndrome. Molecular genetic analysis identified a de novo mutation (c.898C>G) in exon 5 of the ABL1 gene, resulting in a novel missense mutation (p.Gln300Glu). This case emphasizes the importance of considering CHDSKM in the differential diagnosis of children with growth and developmental concerns. The identification of a novel mutation in the ABL1 gene highlights the critical role of early molecular genetic testing, which can facilitate improved management and support for affected individuals and their families.