~ Heidi Moawad MD
A neurological syndrome that used to be called happy puppet syndrome is now more often referred to as Angelman syndrome. Characterized by a number of neurological symptoms, as well as an unusually happy demeanor, the disorder is understood to be caused by an abnormality of chromosome 15.
Symptoms of Angelman syndrome
The symptoms of AS include severe developmental delay that becomes apparent around the age of 12 months, speech delay or absent speech, seizures, hypotonia, ataxia and microcephaly. Children were often described as having a jerky, puppet like gait and an usually happy demeanor that may be accompanied by laughing spells. Patients may have dysmorphic facial features characterized by a prominent chin, an unusually wide smile and deep-set eyes.
The seizures can be partial or generalized and may be atonic or myoclonic. Many authors have describes an EEG pattern characterized by generalized delta activity, which sometimes is considered a trademark of the syndrome.
Management of Angelman syndrome
Management of AS begins with diagnosis, which does require close observation and strong familiarity with childhood neuro developmental syndromes. Clinical management includes seizure control, often with valproic acid, clonazepam or lamotrigine.
Patients may have physical therapy or speech therapy. Medication for management of sleep and/or behavioral issue is sometimes used.
AS may be sporadic, but is more often associated with a deletion of the 15q11.2-q13 chromosome. The chromosome 15q11-13 region is susceptible to imprinting. It does not appear to be clear or consistent at which stage the imprinting takes place. A methylation test can detect deletions of the15q11.2-q13 chromosome. Some patients have a mutation of the ubiquitin-protein ligase E3A (UBE3A) gene, which cannot be detected by the methylation test.
While genetic diagnosis may not alter clinical management, it turns out that families of children diagnosed with AS may carry an increased risk of the disorder on the maternal side.
The genetics is related to imprinting or ‘silencing,’ of the paternal copy of the gene. AS is genetically related to Prader-Willi syndrome, a syndrome with a different set of developmental and neurological symptoms, in which the maternal gene is imprinted, and the paternal gene is expressed.
As management of neuro developmental syndromes has improved, individuals with Angelman syndrome can expect a longer life expectancy than in the past, often living well into middle or old age. This means that individuals with Angelman syndrome can outlive their parents, necessitating long term care. This prospect can be bittersweet for parents of a child who is diagnosed with Angelman syndrome.
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Angelman syndrome: Current and emerging therapies in 2016, Tan WH, Bird LM, Am J Med Genet C Semin Med Genet. 2016 Nov 8
Heidi Moawad MD, author of Careers Beyond Clinical Medicine, is a neurologist and a medical writer. Dr. Moawad currently sees patients in the telemedicine setting and teaches human physiology and global health at John Carroll University in Cleveland, Ohio. An active member of the American Academy of Neurology, Heidi Moawad is on the payment policy committee of the American Academy of Neurology, has written peer reviewed articles, is on the Editorial Board of Neurology Clinical Practice and regularly contributes to several online health websites, including about.com. Dr. Moawad has experince as a clinical neurologist and as a consultant in the health insurance industry.
Dr. Heidi Moawad is a graduate of Case Western Reserve University School of Medicine and trained at Northwestern Evanston Hospital in Evanston, Illinois in Internal Medicine internship and University of Chicago Hospital in Chicago, Illinois in Neurology.