Duplication 17p11.2 in two patients: clinical features and molecular cytogenetic findings

Abstract

Since patients with duplications or deletions involving the Smith-Magenis syndrome (SMS) region at 17p11.2 are thought to arise by the same mechanism of unequal recombination between a repeat sequence that flanks the SMS region (Chen et al., 1997), it is surprising that the duplication patients have been so rarely reported (Magenis et al., 1986; Kozma et al., 1991, Brown et al., 1996; Chen et al., 1997 and 1998; Summers et al., 1998). These patients are most likely underdiagnosed because of lack of defined clinical features and subtlety of the duplication with routine cytogenetic studies. We report two additional patients and review the common physical features in this duplication syndrome.Patient 1 is an 11 month old male with postnatal growth retardation, length at mean for 5 months, and head circumference average for 6 months. He has ptosis of the left eyelid, narrow nose and palate, small mandible, sacral dimple, overlapping toes, decreased tone, and global developmental delay. Patient 2 is a 6 year old female with a history of failure to thrive in early childhood and developmental delay. Height, weight, and head circumference are at the 50th percentile; she has upslanting, narrow palpebral fissures, broad eyebrows, distal joint laxity, and normal neurologic exam. Developmental testing at age 6 showed a full scale IQ of 65, with performance IQ 60 and verbal IQ 78 and behavior consistent with attention deficit hyperactivity disorder.Cytogenetic analyses with G-banding showed duplication of 17p11.2 with a narrow extra gray band in the middle of the G-negative area in the p11.2 region. The duplication was confirmed with a FISH assay using the D17S258 probe (Oncor) for the SMS region. The D17S122 cosmid probe (Oncor), which hybridizes within the region that is duplicated in Charcot-Marie-Tooth type 1A patients, showed a single signal on each chromosome 17 indicating that this region is not duplicated.Comparison of facial features reveals striking similarities between patient 2 and the patient reported by Magenis. It also appears that despite significant early problems with weight gain and development, these patients have fewer problems as they get older and may function in the low normal to borderline range. Detailed clinical descriptions of patients with duplications of 17p11.2 will be helpful in further delineation and recognition of this duplication syndrome.