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15q Duplication Syndrome and Related Disorders.

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GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019.
2016 Jun 16.

Author information

1
Autism & Developmental Medicine Institute, Geisinger Health System, Lewisburg, Pennsylvania
2
Minnesota Epilepsy Group, St Paul, Minnesota
3
University of Connecticut Health Center, Farmington, Connecticut
4
New York University Langone Medical Center, New York, New York
5
Texas A&M University, College Station, Texas
6
University of California Los Angeles Center for Autism Research and Treatment, Los Angeles, California
7
University of California Davis School of Medicine, Sacramento, California
8
University of Tennessee Health Science Center, Memphis, Tennessee
9
Dup15q Alliance, Fayetteville, New York
10
Children's Hospital Boston, Boston, Massachusetts
11
Massachusetts General Hospital, Boston, Massachusetts
12
University of Illinois at Chicago, Chicago, Illinois

Excerpt

CLINICAL CHARACTERISTICS:

15q duplication syndrome and related disorders (dup15q) are caused by presence of at least one extra maternally derived copy of the Prader-Willi/Angelman critical region (PWACR) within chromosome 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 chromosome – idic(15) – typically comprising two extra copies of 15q11.2-q13.1 and resulting in tetrasomy for 15q11.2-q13.1 (~80% of cases); 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% of cases). Dup15q is characterized by hypotonia and motor delays, intellectual disability, autism spectrum disorder (ASD), and epilepsy including infantile spasms. Rarely, dup15q may also be associated with psychosis or sudden unexplained death. Those with maternal idic(15) are typically more severely affected than those with an interstitial duplication.

DIAGNOSIS/TESTING:

The diagnosis of dup15q is established by detection of at least one extra maternally derived copy of the PWACR, a region approximately 5 Mb long within chromosome 15q11.2-q13.1.

MANAGEMENT:

Treatment of manifestations: It is suggested that a multidisciplinary team evaluate infants for motor and speech development and later assist in referrals for appropriate educational programs. Supportive care may include: 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: 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) and failure to follow medication regimen. 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.

GENETIC COUNSELING:

Dup15q caused by: Maternal idic(15) has been 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; Maternal interstitial 15q11.2-q13.1 duplication has been de novo in 85% of probands and inherited from the mother in 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 diagnosis 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 dup15q.

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