KBG syndrome: An Australian experience.

Area of Science:

• Genetics and Human Diseases
• Developmental Biology

Background:

• KBG syndrome, a rare genetic disorder, is associated with heterozygous mutations in the ANKRD11 gene.
• Over 100 cases have been documented, expanding the known clinical spectrum of the syndrome.

Purpose of the Study:

• To present a cohort of 18 individuals with KBG syndrome from 13 families.
• To identify novel ANKRD11 variants and explore genotype-phenotype correlations.
• To highlight key clinical features and emphasize the need for comprehensive examination.

Main Methods:

• Clinical evaluation of 18 KBG-affected individuals.
• Genetic analysis to identify mutations in the ANKRD11 gene.
• Detailed examination of dental, skeletal, and other systemic features.

Main Results:

• Sixteen individuals harbored pathogenic ANKRD11 mutations, including nine novel heterozygous variants.
• Consistent features included intellectual disability, macrodontia, broad forehead, hypertelorism, and prominent nasal bridge.
• Distinctive findings included malrotation of abdominal viscera, basal ganglia calcification, and osteopenia in some patients.

Conclusions:

• ANKRD11 mutations are confirmed as specific to KBG syndrome, impacting neural, cardiac, and skeletal development.
• Thorough dental and skeletal evaluations are crucial for diagnosing and managing KBG syndrome.
• Further case descriptions are needed to fully delineate the neurological and behavioral phenotype.