PEDBASE.org - The Pediatric Database - Detailed information of ANGELMAN SYNDROME

ANGELMAN SYNDROME

DEFINITION:

A chromosomal disorder resulting in a syndrome characterized by dysmorphic facial features with neurological and behavioural manifestations.

EPIDEMIOLOGY:

incidence: 1/20,000
age of onset:
- first year of life (gross motor delay & microbrachycephaly)
risk factors:
- maternally-derived de novo deletion of chromosome 15q11-13
- M= F

PATHOGENESIS:

1. Historical Perspectives

first reported in 1965 by Harry Angelman, an English general Paediatrician, in 3 children - called "puppet children" (Dev. Med. Child. Neurol. 7:681 [1965])
called "Happy Puppet Syndrome" by Bower and Jeavons (Arch. Dis. Child. 43: 298 [1967])

2. Genetic Defect

1. Cytogentic Findings (Anomaly (%))

interstitial deletion (maternally-derived de novo deletion of chromosome 15q11-13)- 75-80%
no cytogenetic anomaly found (10-15%)
rearrangement of maternal chromosome 15 (5%)
uniparental disomy (both chromosome 15's from father) - 3%

CLINICAL FEATURES:

1. Neurological Manifestations

gross motor developmental delay (100%)
severe mental retardation (100%)
ataxia +/- wide-based stiff gait (100%)
absent speech (98%)
truncal hypotonia (90%)
limb hypertonia +/- flexion contractures (85%)
hyperreflexia (85%)
seizures (begin in infancy to 2nd year of life and tend to occur in clusters) - 80%

2. Facial Dysmorphisms*

pointed chin +/- prognathism (95%)
brachycephaly with flattened occiput (90%)
blue eyes (88%)
macrostomia (large mouth) - 75%
tongue protrusion (70%)
blond hair (65%)
widely-spaced teeth (60%)
strabismus (40%)
occipital groove (35%)
bowed primary dentation (35%)
Others: head circumference <25th%, thin upper lip, mid- facial hypoplasia, deep set eyes, decreased pigment of choroid and iris

* absent at birth but become evident by 5 years of age

3. Behavioural Manifestations

jerky movements (develop by 1 year of age)
tongue thrusting and mouthing
hand flapping
hyperactivity & hypermotor behaviours
sleep disturbances
miserable babies
paroxysms of laughter (develop at 3-4 years of age)

4. Musculoskeletal Manifestations

scoliosis (10%) - onset by 5 years of age and progressive
arms flexed at the elbows and upheld
small hands and feet

5. Other Manifestations

skin hypopigmentation
feeding problems (75%)

INVESTIGATIONS:

1. Imaging Studies

1. CT/MRI

mild cortical atrophy
mild generalized ventricular enlargement

2. EEG

large amplitude slow wave activity (4-6 cycles/sec) which persists and is unrelated to drowsiness
very large amplitude slow wave activity (2-3 cycles/sec) occurring in runs and more prominent anteriorly - spikes or sharp waves mixed with large amplitude 3-4 cycles /sec components seen posteriorly and usually on passive eye closure
findings less evident with age

MANAGEMENT:

1. Supportive

no treatment for underlying disease
multidisciplinary approach
- Paediatrics, Neurology, Orthopedics
- physiotherapy and adaptive devices
- non-speaking methods of communication
- surgery for flexion contractures
- genetic counselling

2. Prognosis

most reach adulthood
basic self-care skills are needed throughout adulthood
severity of seizures tends to decrease with age

ADDITIONAL REFERENCES:

1. J. Med. Gen 29:412 (1992)

2. Angelman Syndrome Support Group of Canada

3. Am. J. of Med. Gen. 35:314 (1990)

INTERNET LINKS:

Angelman Syndrome: A Parent's Guide
Angelman Syndrome Foundation, USA
Angels Among Us

Pediatric Database - ANGELMAN SYNDROME

Pediatric Organization - Pedbase [at] Gmail.com