Levodopa responsive Parkinsonism in adults with Angelman Syndrome

E6 associated protein is an E3 ubiquitin ligase encoded by the gene Ube3a. Deletion orloss of function of the maternally inherited allele of Ube3a leads to Angelman syndrome.In the present study, we show that maternal loss of Ube3a (Ube3am-/p+) in the mousemodel leads to motor deficits that could be attributed to the dysfunction of thenigrostriatal pathway. The number of tyrosine hydroxylase positive neurons in thesubstantia nigra was significantly reduced in Ube3am-/p+ mice as compared to the wildtype counterparts. The Ube3am-/p+ mice performed poorly in behavioral paradigmssensitive to nigrostriatal dysfunction. Even though the tyrosine hydroxylase staining wasapparently same in the striatum of both genotypes, the presynaptic and postsynapticproteins were significantly reduced in Ube3am-/p+ mice. These findings suggest that theabnormality in the nigrostriatal pathway along with the cerebellum produces the observedmotor dysfunctions in Ube3am-/p+ mice.

Shalaka A. Mulherkar and Nihar Ranjan Jana

Cellular and Molecular Neuroscience Laboratory, National Brain Research Centre,Manesar, Gurgaon - 122 050, India

Manifestations in Institutionalised Adults with Angelman Syndrome Due to Deletion
Tis Saadanam et al.
American Journal of Medical Genetics.
70: 415-420 (1997)

Wiebe Braam, Robert Didden, Marcel G. Smits and Leopold M. G. Curfs

J Child Neurol 2008; 23; 649

Previous studies suggested that melatonin improves sleep in insomniac patients with Angelman syndrome. To assess the efficacy of melatonin, a randomized placebo-controlled study was conducted in 8 children with Angelman syndrome with idiopathic chronic insomnia. After a 1-week baseline period, patients received, depending on age, either melatonin 5 or 2.5 mg, or placebo, followed by 4 weeks of open treatment. Parents recorded lights off time, sleep onset time, wake-up time, and epileptic seizures in a diary. Salivary melatonin levels were measured at baseline and the last evening of the fourth treatment week. Melatonin significantly advanced sleep onset by 28 minutes, decreased sleep latency by 32 minutes, increased total sleep time by 56 minutes, reduced the number of nights with wakes from 3.1 to 1.6 nights a week, and increased endogenous salivary melatonin levels. Parents were satisfied with these results. Indications that melatonin dose in Angelman syndrome patients should be low, are discussed.

Multi-institutional study on the correlation between chromosomal abnormalities and epilepsy

Tomohiro Kumada et al

Brain & Development 27 (2005)
127-134

Neurological aspects of the Angelman syndrome

Charles Williams

Brain & Development
27 (2005) 88-94

Postural rhythmic muscle bursting activity in Angelman syndrome

Bernard Dan & Guy Cheron