Gene Reviews Overview of Dup15q Syndrome, Angelman Syndrome & the Critical Region

Quick Overview

Dup15q Syndrome is a genetic disorder characterized by duplications of a specific region on chromosome 15. It is associated with a range of clinical features including hypotonia (low muscle tone), developmental delay, intellectual disability, autism, and epilepsy. The syndrome can be diagnosed through genetic testing such as microarray or FISH. Children with Dup15q Syndrome often have motor delays and may require support for walking. Autism is common in individuals with the syndrome, and epilepsy affects more than 50% of patients. Sleep disturbances and gastrointestinal symptoms such as constipation and reflux are also prevalent. There is ongoing research into the risk of Sudden Unexpected Death in Epilepsy (SUDEP) in individuals with Dup15q Syndrome. A national clinics consortium has been established to improve understanding and management of the syndrome.

Introduction

In this talk, we will provide an overview of Dup15q Syndrome and Angelman Syndrome, as well as the critical region on chromosome 15. These topics were discussed at the 2016 ASF-Dup15q Scientific Symposium by Stormy Chamberlain and Ron Thibert.

Genetics of Chromosome 15

Humans have 22 pairs of autosomes and two pairs of sex chromosomes. Chromosome 15 is one of the autosomes and is regulated by a process called genomic imprinting. This means that certain genes on chromosome 15 are expressed exclusively from one parental allele.

Angelman Syndrome

Angelman Syndrome is a brain disorder characterized by epilepsy, sleep disturbance, developmental delays, movement disorders, anxiety, and gastrointestinal symptoms. It is caused by a deletion or mutation of the UBE3A gene on the maternal allele of chromosome 15.

Dup15q Syndrome

Dup15q Syndrome is a genetic disorder characterized by an extra copy of the critical region on chromosome 15. This can occur through interstitial duplications or isodicentric duplications. Dup15q Syndrome is associated with hypotonia, global developmental delay, intellectual disability, autism, epilepsy, and motor impairments.

Clinical Features

Children with Dup15q Syndrome often have hypotonia, which can lead to motor delays and impairments. They may also have global developmental delay and intellectual disability. Autism is very prevalent in individuals with Dup15q Syndrome, with more than 50% of individuals meeting criteria for autism. Epilepsy is also common, with a rate of about 50%. Sleep disturbances, gastrointestinal symptoms, and anxiety are also frequently observed in individuals with Dup15q Syndrome.

SUDEP (Sudden Unexpected Death from Epilepsy)

There have been reports of SUDEP in individuals with Dup15q Syndrome, but the rate of SUDEP is comparable to that of other populations with epilepsy and neurological dysfunction. More research is needed to understand the mechanisms and risk factors for SUDEP in individuals with Dup15q Syndrome.

Conclusion

Dup15q Syndrome and Angelman Syndrome are genetic disorders associated with the critical region on chromosome 15. These syndromes are characterized by a range of clinical features, including hypotonia, developmental delays, intellectual disability, autism, epilepsy, and motor impairments. More research is needed to better understand these syndromes and improve clinical care for individuals with Dup15q Syndrome and Angelman Syndrome.