16p11.2 Recurrent Deletion

Excerpt

Clinical characteristics: The 16p11.2 recurrent deletion phenotype is characterized by motor speech disorder, language disorder, motor coordination difficulties, psychiatric conditions, and autistic features. While most, if not all, individuals with the 16p11.2 recurrent deletion experience some degree of developmental delay, the severity varies significantly. Most affected individuals do not have intellectual disability (defined as an IQ of <70), but many have below average cognition and learning disabilities in both verbal and nonverbal domains. Obesity is a feature of this disorder and generally emerges in childhood; BMI in individuals with the 16p11.2 recurrent deletion is significantly higher than in the general population by age five years. Seizures are observed in approximately 25% of individuals with the recurrent deletion. Vertebral anomalies, hearing impairment, macrocephaly, and cardiovascular malformation have each been observed in some individuals. Clinical follow-up data from adults suggests that the greatest medical challenges are obesity and related comorbidities that can be exacerbated by medications used to treat behavioral and psychiatric problems.

Diagnosis/testing: The diagnosis of 16p11.2 recurrent deletion is established by detection of a heterozygous ~593-kb recurrent deletion at the approximate position of chr16:29638676-30188531 in the reference genome (NCBI Build 38).

Management: Treatment of manifestations: Treatment should be targeted to the specific deficits identified. Full developmental assessment, including neuropsychological testing by a clinical psychologist, is strongly suggested to establish neurodevelopmental needs and treatment recommendations. Standard treatment by a neurologist for seizures or movement disorders. Because of the high risk of obesity beginning in adolescence, encourage healthy eating habits with attention to portion size and an active lifestyle from a young age. Routine management of vertebral anomalies, hearing loss, and congenital heart defects.

Surveillance: Routine surveillance of growth parameters and calculation of BMI after age two years. Monitor developmental progress and educational needs and provide behavioral assessment at each visit. Monitor those with seizures as clinically indicated and monitor for any new neurologic changes, scoliosis, or hearing loss. For those with obesity, monitor blood pressure and fasting blood glucose.

Genetic counseling: The 16p11.2 recurrent deletion is de novo in most probands. Less commonly, the deletion is transmitted from a parent to a child in an autosomal dominant manner.

Once a 16p11.2 recurrent deletion has been identified in a family member, prenatal and preimplantation genetic testing are possible. Interpretation of results from prenatal testing is challenging given the inherent difficulty in accurately predicting the phenotype.