Phenotypic spectrum in patients with 16p11.2 deletion: a single tertiary centre experience in Türkiye

The 16p11.2 deletion is one of the most frequent recurrent copy number variations associated with a broad neurodevelopmental and phenotypic spectrum. Despite its relatively well-characterized genomic region, clinical expressivity remains highly variable, posing challenges for diagnosis and management.

We conducted a retrospective single-centre study of 25 individuals with molecularly confirmed 16p11.2 deletions, including 13 males (52%), 12 females (48%), and 7 familial (28%). Both de novo and inherited cases were included. The main testing method was chromosomal microarray, although karyotyping and additional tests such as sequencing and trinucleotide repeat testing were also utilized. Comprehensive clinical data were collected from medical records, including neurodevelopmental, neuropsychiatric, metabolic, skeletal, and systemic features.

The majority of the cases had the typical ~600 kilobase deletion while two had distal ~220kb deletion. One patient was found to have a double genetic diagnosis. Developmental delay was almost universal in the probands, with expressive language significantly more impaired than receptive language abilities. Intellectual disability / learning difficulties and language problems were observed in 18/25 (72%) cases. Around half of the probands showed obesity and related hyperphagia. Autism spectrum disorder, attention deficit hyperactivity disorder, stereotypic movements, and aggressive behaviour were frequently reported. Epilepsy was present in thirteen patients (52%), with electroencephalographic abnormalities supporting generalized or focal epileptiform activity. Dysmorphic facial features and skeletal anomalies such as pes equinovarus, syndactyly, and scoliosis were variably present. Brain magnetic resonance imaging revealed abnormalities in several patients, including hypoplasia of the corpus callosum and intracranial hypertension. Additional systemic findings included hepatic steatosis, constipation, and ophthalmologic anomalies. Parental testing revealed asymptomatic or mildly affected carriers in multiple cases.

Our findings emphasize the broad and heterogeneous clinical spectrum of 16p11.2 deletions in a Turkish cohort. Early recognition, multidisciplinary evaluation, and family-based genetic counselling are essential for timely diagnosis and optimal care of affected individuals.