Laina Lusk, MMSc, CGC, Vanessa Vogel-Farley, BA, Charlotte DiStefano, PhD, and Shafali Jeste, MD.
Clinical characteristics.
Maternal 15q duplication syndrome (maternal dup15q) is characterized by hypotonia and motor delays, intellectual disability, autism spectrum disorder (ASD), and epilepsy including infantile spasms. Rarely, maternal dup15q may also be associated with psychosis or sudden unexplained death. Those with a maternal isodicentric 15q11.2-q13.1 supernumerary chromosome are typically more severely affected than those with an interstitial duplication.
Diagnosis/testing.
The diagnosis of maternal dup15q is established by detection of at least one extra maternally derived copy of the Prader-Willi/Angelman critical region, a region approximately 5 Mb long within chromosome region 15q11.2-q13.1. The extra copy or copies most commonly arise by one of two mechanisms:
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A maternal isodicentric 15q11.2-q13.1 supernumerary chromosome – idic(15) – typically comprising two extra copies of 15q11.2-q13.1 and resulting in tetrasomy for 15q11.2-q13.1 (~60-80%);
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A maternal interstitial 15q11.2-q13.1 duplication that typically includes one extra copy of 15q11.2-q13.1 within chromosome 15, resulting in trisomy for 15q11.2-q13.1 (~20-40%).
Management.
Treatment of manifestations: Multidisciplinary team evaluation of motor and speech development and to assist in referrals for appropriate educational programs. Supportive care may include: feeding therapy, occupational and physical therapy, alternative and augmentative communication, behavioral therapy (e.g., applied behavioral analysis therapy), psychotropic medications for behavioral manifestations, and standard management for seizures.
Surveillance: Growth and nutritional assessment at each visit. Periodic: neurodevelopmental and/or developmental/behavioral assessments, and monitoring for evidence of seizures and/or change in seizure type.
Agents/circumstances to avoid: Seizure triggers (e.g., sleep deprivation, stress).
Evaluation of relatives at risk: Consider genetic testing of sibs of a proband (known to be at increased risk for an inherited maternal interstitial 15q11.2-q13.1 duplication) in order to refer those with the interstitial duplication promptly for multidisciplinary team evaluation and developmental support.
Genetic counseling.
Maternal dup15q caused by:
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Maternal idic(15).De novo in all affected individuals reported to date; thus, risk to sibs is low, but presumed to be marginally greater than in the general population because of the possibility of maternal germline mosaicism;
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Maternal interstitial 15q11.2-q13.1 duplication. De novo in approximately 85% of probands and inherited from the mother in approximately 15%. If the mother has the 15q interstitial duplication, the risk to each child of inheriting the duplication is 50%.
Prenatal testing or preimplantation genetic testing using chromosomal microarray (CMA) will detect the 15q interstitial duplication; however, prenatal test results cannot reliably predict the severity of the phenotype even in a pregnancy known to be at increased risk for maternal dup15q.
