Angelman Syndrome: Consensus for Diagnostic Criteria
The information and tables included below are part of a consensus paper on AS that was published in 2006 (American Journal of Medical Genetics 140A:413–418) and was the result of a work group convened by the Scientific Advisory Committee of the Angelman Syndrome Foundation. Table 1 summarizes the developmental history and table 2 summarizes the main clinical features.
There are no precise features that allow the physician to definitively make the diagnosis but there are characteristic features that occur with high probability in the syndrome.
Table 1. 2005: Developmental History and Laboratory Findings in AS
- Normal prenatal and birth history with normal head circumference and absence of major birth defects.Feeding difficulties may be present in the neonate and infant.
- Developmental delay evident by 6-12 months of age, sometimes associated with truncal hypotonus. Unsteady limb movements and/or increased smiling may be evident.
- Delayed but forward progression of development (no loss of skills)
- Normal metabolic, hematologic and chemical laboratory profiles
- Structurally normal brain using MRI or CT (may have mild cortical atrophy or dysmyelination)
* These findings are useful as inclusion criteria but deviations should not exclude diagnosis.
Table II. 2005: Clinical Features of AS
A. Consistent (100%)
- Developmental delay, functionally severe
- Movement or balance disorder, usually ataxia of gait and/or tremulous movement of limbs. Movement disorder can be mild. May not appear as frank ataxia but can be forward lurching, unsteadiness, clumsiness, or quick, jerky motion.
- Behavioral uniqueness: any combination of frequent laughter/smiling; apparent happy demeanor; easily excitable personality, often with uplifted hand-flapping or waving movements; hypermotoric behavior
- Speech impairment, none or minimal use of words; receptive and non-verbal communication skills higher than verbal ones
B. Frequent (nearly 80%)
- Delayed, disproportionate growth in head circumference, usually resulting in microcephaly (≤2 S.D. of normal OFC) by age 2 years. Microcephaly is more pronounced in those with 15q11.2-q13 deletions.
- Seizures, onset usually < 3 yrs. of age. Seizure severity usually decreases with age but the seizure disorder lasts throughout adulthood.
- Abnormal EEG, with a characteristic pattern, as mentioned in the text. The EEG abnormalities can occur in the first 2 years of life and can precede clinical features, and are often not correlated to clinical seizure events.
C. Associated (20-80%)
- Flat occiput
- Occipital groove
- Protruding tongue
- Tongue thrusting; suck/swallowing disorders
- Feeding problems and/or truncal hypotonia during infancy
- Wide mouth, wide-spaced teeth
- Frequent drooling
- Excessive chewing/mouthing behaviors
- Hypopigmented skin, light hair and eye color compared to family), seen only in deletion cases
- Hyperactive lower extremity deep tendon reflexes
- Uplifted, flexed arm position especially during ambulation
- Wide-based gait with pronated or valgus-positioned ankles
- Increased sensitivity to heat
- Abnormal sleep wake cycles and diminished need for sleep
- Attraction to/fascination with water; fascination with crinkly items such as certain papers and plastics
- Abnormal food related behaviors
- Obesity (in the older child)
Charlie Williams, MD