Spastic paraplegia with iron deposits in the basal ganglia: A new X‐linked mental retardation syndrome

Abstract

We report on a family with X-linked mental retardation (XLMR) and severe spastic paraplegia. Appearance is normal but there is severe involvement of the lower limbs (affected relatives never walked), with minimal involvement of the upper limbs and unusual MRI findings including macrogyria, white matter hypoplasia, lack of myelination and a markedly increased paramagnetic signal suggestive of iron deposition. Linkage studies documented possible linkage, with no recombination, between the disease locus and DXS424. A 7-point linkage analysis yielded a maximum LOD score of 1.9, (theta = 0.00) for three loci spanning Xq22-q25. The combination of the unusual clinical and MRI findings and the tentative localization to a region different than other XLMR syndromes with spastic paraplegia, provide good evidence that this is a new XLMR syndrome.

A new X linked mental retardation (XLMR) syndrome with short stature, small testes, muscle wasting, and tremor localises to Xq24-q25

“…The remaining XLMR syndromes (Christianson et al ,12 Gustavson (MIM 309555), Arena et al ,13 Arts (MIM 301835), Christian (MIM 309620), Chudley et al ,14 and Cowchock-Fishbeck (MIM 310200), which overlap the present localisation, do not have significant clinical similarities. Only molecular studies following the cloning of these several disorders will resolve the issue of possible allelism for this group of XLMR disorders.…”

X linked severe mental retardation, craniofacial dysmorphology, epilepsy, ophthalmoplegia, and cerebellar atrophy in a large South African kindred is localised to Xq24-q27

“…However, both syndromic and non-syndromic forms of XLMR have overlapping mapping limits (fig 8). Among the XLMR syndromes mapped to Xq24-q27, Arena syndrome has the most similar phenotype 14. Both entities have absent speech, absence or loss of ambulation, incontinence, truncal ataxia, contractures, and hypoplasia or atrophy of the cerebellum and brain stem.…”

X-linked disorders with cerebellar dysgenesis

“…Only one of the affected males developed seizures and showed changes in the basal ganglia suggesting iron deposits. The condition was mapped to Xq23-q24 [82]. …”