The Ash Twins Blog

In his original report “’Puppet Children’: A report on three cases” (1965), Angelman identified many of the key features of Angelman syndrome (AS):

Their flat heads, jerky movements, protruding tongues and bouts of laughter give them a superficial resemblance to puppets, an unscientific name but one which may provide for easy identification. It will be seen that all these children possess a number of characteristic features in common and may be summarised as follows:

1. A horizontal depression in the occipital region of the skull, present at birth. Also brachycephaly associated with microcephaly, becoming more obvious as growth proceeds, but not due to premature fusion of the coronal sutures.
2. A varying degree of primary optic atrophy, associated with incomplete development of the choroid.
3. Abnormal air encephalograms indicating some degree of cerebral atrophy associated with ventricular dilatation.
4. Very frequent fits resembling a hypsarrhythmic state and a profound degree of mental retardation.
5. Easily provoked and prolonged paroxysms of laughter.
6. Ataxia, with weakness of the limbs and trunk resembling that seen in cerebellar deficiency.
7. Ability to protrude the tongue to an unusual degree.

Add to this a profound developmental delay, speech impairment, and abnormal sleep patterns, and a near-complete picture of Angelman syndrome is formed (Figure 1) (Dan 2009).

Figure 1 – Children with Angelman Syndrome. Images courtesy (Clay-Smith & Laan 2003)

As AS patients reach adulthood, their behavior becomes quieter and they are less hyperactive, but their sociability and easy laughter persists (Clay-Smith & Laan 2003). Some adult AS patients become aggressive, especially if frustrated by communication difficulties. Puberty occurs normally in AS patients, and some have intact fertility. The distinct AS facial features become even more pronounced. Most patients develop muscular rigidity and scoliosis, and many patients become obese.

Inspection of the gross neuroanatomy reveals a small brain with some atrophy most prominent in the cerebellum (Jay et al 1991). Golgi staining of AS cortex shows a prominent decrease in dendritic arborization and spine number in layer 3 and 5 pyramidal neurons. Decreased GABA levels are present in cerebellum, and increased glutamate levels are present in cerebral cortex.

Angelman syndrome is an uncommon neurodevelopmental syndrome, with an estimated prevalence of 1-in-10,000 to 1-in-12,000 individuals (Petersen et al 1995; Steffenberg et al 1996). The only potential risk factor identified for Angelman Syndrome is assisted reproductive technology i.e. in vitro fertilization, but given the rarity of AS and imprinting disorders in general there is currently insufficient evidence to establish the association (Owen & Segars 2009).

There are as yet no good treatments for AS. Seizures can be treated with antiepileptic medication, but they are conspicuously difficult to manage (Williams 2005). Physical therapy may help with the motor deficits. Melatonin can be prescribed to minimize night-time sleeplessness.

Clayton-Smith J, Laan L. (2003) “Angelman syndrome: a review of the clinical and genetic aspects.” J Med Genet. 40(2):87-95. Review.

Dan B. (2009) “Angelman syndrome: current understanding and research prospects.” Epilepsia. 50(11):2331-9.

Jay V, Becker LE, Chan FW, Perry TL Sr.(1991) “Puppet-like syndrome of Angelman: a pathologic and neurochemical study. Neurology. 41(3):416-22.

Owen CM, Segars JH (2009) “Imprinting disorders and assisted reproductive technology.” Semin Reprod Med. 27(5):417-28

Petersen MB, Brondum-Nielsen K, Hansen LK, Wulff K. (1995) “Clinical, cytogenetic, and molecular diagnosis of Angelman syndrome: estimated prevalence rate in a Danish county.” Am J Med Genet 60:261–2.

Steffenburg S, Gillberg CL, Steffenburg U, Kyllerman M. (1996) “Autism in Angelman syndrome: a population-based study.” Pediatr Neurol 14:131–6.

Williams C (2005) “Neurological aspects of the Angelman syndrome” Brain & Development 27: 88–94