|Rett syndrome||medical dictionary|
<neurology, syndrome> The syndrome that bears his name was first described by Rett (1966, 1977). Hagberg (1985) estimated the frequency of the disorder to be about 1:15,000 in southwestern Sweden. Among girls aged 0 to 18 years in North Dakota, Burd et al. (1991) found the frequency of Rett syndrome to be 1 in 19,786.
Hagberg (1983) described 35 patients, all girls from 3 countries (France, Portugal and Sweden), with a uniform and striking, progressive encephalopathy. After normal development up to the age of 7 to 18 months, developmental stagnation occurred, followed by rapid deterioration of high brain functions. Within 1.5 years this deterioration progressed to severe dementia, autism, loss of purposeful use of the hands, jerky truncal ataxia, and 'acquired' microcephaly. Thereafter, a period of apparent stability lasted for decades. Additional neurologic abnormalities intervened insidiously, mainly spastic paraparesis, vasomotor disturbances of the lower limbs, and epilepsy. A striking deceleration of growth has been found across all measurements in 85 to 94% of girls with Rett syndrome and may provide the earliest clinical indication of this disorder.
The presence of metatarsal and metacarpal abnormalities in some patients with Rett syndrome prompted radiologic studies of 17 cases. Short fourth and/or fifth metatarsals were identified in 11 (65%) and short fourth and/or fifth metacarpals in 8 of 14 (57%). Reduced bone density in the hands was found in 12 of 14 cases (86%).
The exclusive involvement of females is best explained by X-linked dominant inheritance with lethality in the hemizygous males. By this hypothesis, all cases are new mutations. One instance of 2 affected half-sisters born to the same mother is known. This is explicable on the basis of gonadal mosaicism or X-autosome translocation in the mother. However, no chromosomal abnormality was found. Another possible mechanism for only female cases is that called metabolic interference. According to this suggestion, the homozygous female and the hemizygous male are normal, the heterozygous female is abnormal because of an adverse interaction of the gene products from the 2 X chromosomes. Because of lyonization, these products would be produced in different cells.
Light-microscopy shows evidence of white matter disease and ultrastructurally, many neurones and oligodendroglia contained membrane-bound electron-dense inclusions with a distinct lamellar and granular substructure with a striking decrease in the dendritic trees of selected cortical areas, chiefly projection neurones of the motor, association, and limbic cortices.
Clinical features: progressive encephalopathy, severe dementia, autism, loss of purposeful hand use, jerky truncal ataxia, spastic paraparesis, vasomotor disturbances of legs, seizures and acquired microcephaly.
Incidence: approximately 1 in 15,000
(22 Jan 1998)
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