Maternal 15q Duplication Syndrome

July 15, 2021

Laina Lusk, MMSc, CGC, Vanessa Vogel-Farley, BA, Charlotte DiStefano, PhD, and Shafali Jeste, MD.

Clinical characteristics.

Maternal 15q  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  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 , a region approximately 5 Mb long within  region 15q11.2-q13.1. The extra copy or copies most commonly arise by one of two mechanisms:

  • A maternal isodicentric 15q11.2-q13.1 supernumerary  – idic(15) – typically comprising two extra copies of 15q11.2-q13.1 and resulting in tetrasomy for 15q11.2-q13.1 (~60-80%);
  • A maternal interstitial 15q11.2-q13.1  that typically includes one extra copy of 15q11.2-q13.1 within  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  (known to be at increased risk for an inherited maternal interstitial 15q11.2-q13.1 ) in order to refer those with the interstitial duplication promptly for multidisciplinary team evaluation and developmental support.

Genetic counseling.

Maternal dup15q caused by:

  • 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 ;
  • Maternal interstitial 15q11.2-q13.1 . 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  using  (CMA) will detect the 15q interstitial ; however, prenatal test results cannot reliably predict the severity of the  even in a pregnancy known to be at increased risk for maternal dup15q.

Read Full Gene Review

 

Related Posts

Consistent, convergent pathways link two forms of autism

Consistent, convergent pathways link two forms of autism

Consistent, convergent pathways link two forms of autism BY ANGIE VOYLES ASKHAM  / Spectrum News / 15 NOVEMBER 2022https://doi.org/10.53053/OWUW9177 The brains of people with a duplication of the 15q11-13 chromosomal region have dysregulated gene expression,...

LADDER Database Family-friendly Reports

LADDER Database Family-friendly Reports

LADDER Database Family-friendly Reports LADDER shares de-identified information (which means it cannot be traced back to you or your family) from the LADDER database with approved researchers. When research projects using LADDER data result in publications, we share...