Patient with large 17p11.2 deletion presenting with Smith-Magenis syndrome and Joubert syndrome phenotype

We report on a 22-year-old woman carrying a del(17)(p11.2p12) and presenting with the clinical manifestations of both Smith-Magenis syndrome (SMS) and Joubert syndrome (JS). Her facial anomalies, brachydactyly, severe mental retardation, and self-injuring behavior could be attributed to SMS, whereas the cerebellar vermis hypoplasia, hypotonia, ataxic gait, developmental delay, and abnormal respiratory pattern were suggestive of JS. By fluorescent in situ hybridization analyses with Yeast Artificial Chromosomes (YAC) mapping to the 17p11.2 region, as well as locus-specific probes generated through a novel procedure, we could establish that the deletion encompasses a 4-Mb interval with centromeric and telomeric breakpoints at loci D17S793 and D17S953, the latter close to the locus Charcot Marie Tooth 1A (CMT1A)-REP. The deletion differs from that commonly found in SMS in its telomeric boundary, which is more distal than usually observed. The presence of JS phenotype in our patient and the detection of an unusual SMS deletion might suggest the presence of a JS gene in close proximity to the SMS locus.