SSBP Information Sheet
SMITH MAGENIS SYNDROME

First description:
In 1982, Anne Smith and her colleagues described the ‘unique finding’ of two unrelated males with similar physical characteristics and the same chromosomal abnormality. It was not until four years later (after a subsequent reporting of a female with the syndrome) that the clinical features of the syndrome were fully investigated and described (Smith et al., 1986; Stratton et al., 1986). The syndrome later became known as Smith-Magenis syndrome (SMS).

Incidence/prevalence
It is believed that there are many unreported cases of Smith-Magenis syndrome. As a result, Greenberg et al. (1991) suggest that the literature is misleading in terms of its reported incidence. Greenberg et al. propose a minimum birth prevalence of one in 1 in 25,000 births and suggests that SMS may be as common as Prader-Willi syndrome (1 in 16,000, Burd et al., 1990).

Genetic aspects:
Nearly all cases of Smith-Magenis syndrome occur de novo (Zori et al., 1993). SMS is a microdeletion syndrome associated with an interstitial deletion of the short arm of chromosome 17, specifically band 17(p11.2p11.2)(Smith et al., 1986). Recent research has suggested that SMS is caused by a mutation in a single candidate gene, RAI1 (Slager et al., 2003).

Physical phenotype:
Individuals with Smith Magenis syndrome are reported to have characteristic facial features that coarsen with development. Their face is generally square in shape with a flattened mid-face. They also have a broad mouth with full lips (the upper said to be shaped like a ‘cupid’s bow’), heavy brows, deep set eyes and a short nose with a broad base and full tip. Brachycephaly is also seen (congenital malformation of the skull resulting in a short broad appearance). Other common physical characteristics associated with the syndrome include short broad hands with in-bent fingers, small toes, infantile hypotonia, failure to thrive in infancy and a hoarse deep voice in older children, adolescents and adults. It has been reported that up to 75% of patients with SMS have signs of peripheral neuropathy and therefore decreased tendon reflexes and insensitivity to pain are common (Greenberg, et al., 1996). Variable characteristics reported include; hearing loss, visual problems including iris coloboma (absence or defect of the ocular tissue affecting function), scoliosis, cardiac defects, hypercholesterolemia and abnormal EEGs without overt seizures.

Cognitive characteristics:
Although the level of intellectual disability in SMS is variable, the majority of individuals are reported to fall in the moderate range of cognitive impairment, with varied adaptive skills. The severity of the learning disability correlates with the size of the 17p11 deletion. Additionally, speech and language development is markedly delayed, particularly in relation to expressive language (Greenberg et al., 1991, 1996). Children and adults with SMS have been described as displaying a good memory together with good perceptual skills and excellent computer skills.

Behavioural aspects:
Neonates with SMS are usually described as placid, "floppy" and feed with difficulty.

Older individuals with SMS are often described as loving, caring, friendly and eager to please, with a good sense of humour. They like attention and particularly enjoy interacting with adults. However, high levels of impulsivity, hyperactivity, irritability and distractibility have been reported in individuals with SMS, together with a particularly high prevalence of other challenging behaviours such as temper tantrums, self-injury and aggression.

An abnormal circadian rhythm of melatonin has been identified in SMS and over sixty per cent of individuals are reported to have severe sleep problems. These difficulties manifest as difficulties falling asleep, shortened sleep cycles, night wakening and daytime sleepiness. An absence of REM sleep has been reported in some patients.

More recently the behavioural characteristic of a spasmodic upper body squeeze or ‘self-hug’ has been described in individuals with SMS. This is demonstrated particularly when the individual is happy or excited (Dykens & Smith, 1998; Finucane et al., 1993, 1994).

Life expectancy:
In the absence of major organ involvement, life expectancy of individuals with the syndrome may be expected to be close to normal. The oldest living person with SMS is currently in her 80s (Smith et al., 2004).

Key references:
Colley, A.F. et al (1990) Five cases demonstrating the distinctive behavioural features of chromosome deletion 17(p11.2p11.2) (Smith-Magenis syndrome). Journal of Paediatrics and Child Health, 26, 17-21.

Greenberg, F., Guzzetta, V., de Oca-Luna, R. M., Magenis, R. E., Smith, A. C. M., Richter, S. F., Kondo, I., Dobyns, W. B., Patel, P. I., & Lupski, J. R. (1991). Molecular analysis of the Smith-Magenis syndrome: A possible contiguous gene syndrome associated with del (17)(p11.2). American Journal of Human Genetics, 49, 1207 - 1218.

J Sloneem, 2004

Link to Smith-Magenis Syndrome Contact Group
Email:
gmc@yolger.fsnet.co.uk - Smith Magenis Foundation