Clinical characteristics: Individuals with the 15q13.3 recurrent deletion may have a wide range of clinical manifestations. The deletion itself may not lead to a clinically recognizable syndrome and a subset of persons with the recurrent deletion have no obvious clinical findings, implying that penetrance for the deletion is incomplete. A little over half of individuals diagnosed with this recurrent deletion have intellectual disability or developmental delay, mainly in the areas of speech acquisition and cognitive function. In the majority of individuals, cognitive impairment is mild. Other features reported in diagnosed individuals include epilepsy (in ~30%), mild hypotonia, and neuropsychiatric disorders (including autism spectrum disorder, attention-deficit/hyperactivity disorder, mood disorder, schizophrenia, and aggressive or self-injurious behavior). Congenital malformations are uncommon.
Diagnosis/testing: The diagnosis of the 15q13.3 recurrent deletion is established in a proband by the presence of a heterozygous recurrent 2.0-Mb deletion at the approximate position of 30.5-32.5 Mb in the reference genome (chr15:30366247-32929476 [GRCh37/hg19]) that includes deletion of 1.5 Mb of unique sequence as well as an additional 500 kb or more of segmental duplications.
Management: Treatment of manifestations: Epilepsy is treated with anti-seizure medication (ASM). The use of valproate has been successful in a number of affected individuals, while oxcarbazepine led to clinical worsening in one affected individual. However, a variety of ASMs may be used. Standard treatment for developmental delay / intellectual disability, neuropsychiatric disorders, congenital anomalies (cardiac and/or renal anomalies), refractive errors, strabismus, and chronic ear infections / glue ear.
Surveillance: Monitor developmental progress / education needs at each visit. Assessment for anxiety, attention, aggressive/self-injurious behavior, and new neurologic manifestations (such as seizures) at each visit. Annual audiology evaluation in infancy and childhood (or as clinically indicated). Ophthalmology evaluation per treating ophthalmologist(s).
Genetic counseling: The 15q13.3 recurrent deletion is inherited in an autosomal dominant manner. Approximately 15% are de novo and approximately 85% are inherited. Offspring of an individual with this deletion have a 50% chance of inheriting the deletion. Although prenatal testing is technically feasible, it is not possible to reliably predict the phenotype based on the laboratory finding of the 15q13.3 recurrent deletion.
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