Two Patients with Angelman Syndrome Followed Beyond 20 Years of Age

Abstract

Purpose: Angelman syndrome is now diagnosed appropriately because of the development of the fluorescence in situ hybridization (FISH) method. We encountered two cases of this syndrome, and the follow‐up studies until adulthood produced some interesting clinical findings. Case Reports: Case 1 was a 23‐year‐old man. Albinism, delayed speech development, hyperactivity, avoidance of eye contact, and hypersalivation were noticed. Cerebral palsy ‐was suspected. He could walk independently by age 2 years but could not speak a single word. At age 3 years, epileptic seizures developed and were observed frequently until age 10 years. At that time, his condition was consistent with epilepsia partialis continua because of tremors of the left hand and a continuation of the electroencephalographic (EEG) findings of spikes on the midtemporal and right central regions. The epileptic attacks were controlled with clonazepam (CZP). A constant happy demeanor has been noticed but outbursts of laughter have not been observed. Diffuse high‐amplitude slow‐wave activity with intermittent spike‐wave discharges, which are the characteristic EEG features of Angelman syndrome, disappeared and spike‐wave‐like discharges over the frontal area were observed thereafter. The present clinical features are severe intellectual disability, happy disposition, clumsy and awkward gait without palsy, oculocutaneous albinism, and semiopened large mouth with protruding tongue and salivation. A chromosomal analysis disclosed 46XYde1(15)(qIl.lql2), and the FISH method detected the deletion of the signal SNRNP.Case 2 was a 20‐year‐old man. Intellectual disability and hyperactivity had been noticed since infancy. Cerebral palsy was suspected. He could walk independently by 3 years and 6 months but could not speak a single word. The initial epileptic seizure occurred at age 2 years and 7 months. However, no seizures were observed after age 9 years. He has had a constant happy demeanor but no outbursts of laughter. At the present, he shows severe intellectual disability, happy disposition, clumsy and awkward gait without palsy, hypopigmented skin color, and semiopened large mouth with protruding tongue and salivation. EEG examination during childhood revealed the characteristic EEG activities of Angelman syndrome, diffuse high‐amplitude slow waves with intermittent spikes. However, at the present, only migratory focal spikes are seen. A chromosomal analysis disclosed 46XY del(l5)(qllq13), and the FISH method revealed a deletion of the SNRNP region. Conclusions: We followed up two patients with Angelman syndrome who were diagnosed with the FISH method. Patients with severe intellectual disability and a constant happy demeanor should be studied with the FISH method. Epileptic attacks were well controlled after adolescence, and the characteristic diffuse high‐amplitude slow‐wave activities disappeared thereafter.