The common SMS deletion region is duplicated in patients with a milder, predominantly neurobehavioral phenotype and the reciprocal chromosome duplication—dup(17)(p11.2p11.2)
(5,23). Similar to SMS patients with common deletion, subjects with common duplication dup(17)(p11.2p11.2) also manifest marked variability in the physical features and behavioral profile. Clinical findings include dysmorphic craniofacial features, hypotonia and failure to thrive, oropharyngeal dysphasia, neurocognitive impairment, and behavioral problems including autistic, aggressive, and self-injurious behavior. Structural cardiac anomalies including aortic root enlargement, have been identified. However, the frequency of organ system developmental abnormalities appears to be less than that observed for patients deleted for this genomic interval (i.e., SMS). Sleep disturbances are seen in all patients yet the findings are distinct from those of deletion 17p11.2. It is predicted that the incidence of dup(17)(p11.2p11.2) may be equal to that of SMS given the reciprocal nature of the common rearrangements responsible for the conditions. However, as this duplication is difficult to detect by routine cytogenetic analysis, many of these patients are currently probably not ascertained. Systematic clinical evaluation of a cohort of patients with dup(17)(p11.2p11.2) will be necessary to determine the features most characteristic of this microduplication syndrome.
The relatively high frequency of constitutional genomic disorders in proximal chromosome 17p is further substantiated by the identification of an individual with two distinct megabase-sized DNA rearrangements of this genomic interval. These included both a de novo dup(17)(p11.2p11.2) and an inherited HNPP deletion on the other homolog. These rearrangements were associated with mild delay and a family history of autosomal dominant carpal tunnel syndrome (24).
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