Most patients (90%) with the Smith-Magenis syndrome have interstitial deletions in the short arm of chromosome 17 (17p11.2).  However, it is included here since a few have heterozygous molecular mutations in the RAI1 [2] gene which is located in this region.  While there is considerable phenotypic overlap, individuals with chromosomal deletions have the more severe phenotype as might be expected.  For example, those with RAI1 [2] mutations tend to be obese and are less likely to exhibit short stature, cardiac anomalies, hypotonia, hearing loss and motor delays than seen in patients with a deletion in chromosome 17.  However, the phenotype is highly variable among patients with deletions depending upon the nature and size of the deletion.

The retinoic acid induced 1 gene (RAI1 [2]) codes for a transcription factor whose activity is reduced by mutations within it.

Familial cases are rare and reproductive fitness is virtually zero.  If parental chromosomes are normal, the risk for recurrence in sibs is less than 1%.  Males and females are equally affected.

In Potocki-Lupski syndrome (610883 [1]) there is duplication of the 17p11.2 microdeletion as the reciprocal recombination product of the SMS deletion.