X-linked mental retardation with thin habitus, osteoporosis, and kyphoscoliosis: Linkage to Xp21.3-p22.12

Abstract

We reevaluated a family previously described as having nonspecific X‐linked mental retardation (XLMR) by Snyder and Robinson [1969: Clin Pediatr 8:669–674] (MIM 309583). Clinical and DNA studies were conducted on 17 relatives, including 6 males with mild‐to‐moderate mental retardation, 3 carrier females, and 8 normal males. In contrast to the normal appearance and minimal clinical findings reported 22 years ago, affected males were found to have a characteristic set of clinical findings. These developed gradually over the first 2 decades, and included thin body build with diminished muscle mass, osteoporosis and kyphoscoliosis, slight facial asymmetry with a prominent lower lip, nasal speech, high narrow or cleft palate, and long great toes. Carrier females were clinically normal. Multipoint linkage analysis indicated linkage to markers distal to the 3′ end of DMD (DXS41 and DXS989), with a maximal lod score of 4.7. On the basis of these findings, this entity is redefined as XLMR syndrome. © 1996 Wiley‐Liss, Inc.

New SMS mutation leads to a striking reduction in spermine synthase protein function and a severe form of Snyder-Robinson X-linked recessive mental retardation syndrome

“…Therefore, the data indicate these clinical findings are probably characteristic of SRS. Longer great toes and tall stature could not be evaluated adequately in the adult patient of the present family, but were not observed in the children, suggesting that these clinical presentations may be specific to the first reported family or, as commented previously, may become evident only after puberty 2 3. In addition, neither pectus excavatum nor facial asymmetry was observed in the patients of the family described here.…”

“…*The original family was first reported by Snyder and Robinson 1. It was re-evaluated by Arena et al 2 who provided a more detailed clinical description of five adult males and an additional affected male, 2 years of age. Although clinical data for infancy are not shown, all affected individuals showed delayed development.…”

“…In 1996, Arena et al 2 re-evaluated five affected adult males and evaluated an additional 2-year-old boy. They observed a characteristic combination of clinical features including mild-to-moderate mental retardation, facial asymmetry of the lower face and orbital region, thickened lower lip, nasal dysarthric and/or slow speech, thin habitus with diminished muscle bulk, osteoporosis, kyphoscoliosis, and long hands with hyperextensible fingers.…”

The impact of spermine synthase (SMS) mutations on brain morphology

“…However, upon reevaluation, the affected males were found to have a thin habitus, kyphoscolioses, and long great toes. Distinctive facial features were observed: asymmetry, prominent lower lip, and a high or cleft palate [2]. Additional clinical features including unsteady gait, seizures, nonspecific movement disorder, and abnormal EEG were noted in a follow-up evaluation [3].…”

“…The syndrome was mapped to Xp21.2–p22.2 [2] and subsequent studies identified a splice mutation (c.329+5 G>A) in the spermine synthase ( SMS ) gene which caused low level of intracellular spermine in lymphocytes and fibroblasts and elevated spermidine/spermine ratios in these cells [3]. Recently, a second family with SRS and a novel mutation in SMS was identified [4].…”