Variability in clinical phenotype despite common chromosomal deletion in Smith-Magenis syndrome [del(17)(p11.2p11.2)]

Purpose This report delineates the phenotypic features in a cohort of 58 individuals with Smith-Magenis syndrome (SMS) and compares features of patients with the common microdeletion to those of patients with variable sized deletions, and the three previously reported patients who harbor a mutation in RAI1 (retinoic acid induced 1).Methods From December 1990 thru September 1999, 58 persons with SMS were enrolled in a 5-day multidisciplinary clinical protocol at the General Clinical Research Center (GCRC), Texas Children's Hospital. Each patient had a cytogenetically evident deletion in 17p11.2.Results Of the 51 patients in whom the molecular extent of the chromosomal deletion could be delineated by pulsed-field gel electrophoresis (PFGE) and/or fluorescent in situ hybridization (FISH), 39 (≈76%) had the common SMS deletion. Smaller or larger deletions were seen in ≈12% and ≈10% of patients, respectively, and 1 patient had a complex chromosomal rearrangement including a deletion in 17p11.2. Parent of origin was determined by polymorphic marker analysis in a subset of patients: maternal ≈43%, paternal ≈57%. All patients had impaired cognitive and adaptive functioning and had at least one objective measure of sleep disturbance. Other common features (seen in > 50% of patients) include short stature, ophthalmological, and otolaryngological anomalies, hearing impairment, abnormal EEG, and scoliosis. Cardiac and renal anomalies were seen in ≈45% and ≈19% of patients, respectively. There are no statistically significant differences in the incidence of these abnormalities in patients with the common deletion compared to those patients with smaller or larger sized deletions.Conclusions Despite a common deletion size in 76% of patients with SMS, the only constant objectively defined features among these patients are sleep disturbances, low adaptive functioning, and mental retardation. There is no pathognomonic clinical feature, no characteristic cardiovascular defect, renal anomaly, otolaryngological or ophthalmic abnormality in SMS.

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