A clinical and molecular study of mosaicism for trisomy 17

Trisomy 17 has never been reported in a live birth. We present a case of mosaic trisomy 17 in a male presenting with mental retardation, seizures, attention deficit hyperactivity and autistic disorders, hearing loss, growth retardation, microcephaly, and minor anomalies. Although peripheral blood lymphocyte chromosomes were normal, trisomy 17 was present in the skin fibroblasts. The percentage of abnormal cells appears to have increased from 18% in an initial skin biopsy at age 3 years 8 months to 80% at age 8 years 8 months. Molecular analysis using 13 highly polymorphic markers spanning the length of chromosome 17 demonstrated the extra chromosome 17 in the skin to be of paternal origin. Three alleles were never seen in the trisomic cell line, suggesting that the extra chromosome arose through a mitotic duplication error after conception. Uniparental disomy was excluded in the euploid blood sample. Although Smith-Magenis syndrome involves a deletion of proximal 17p, some of the clinical features of this mosaic trisomy 17 patient, such as decreased REM sleep and increased tolerance to pain, are suggestive of phenotypic features observed in Smith-Magenis syndrome. We speculate that there are dosage-sensitive genes located in 17p11.2 that produce these phenotypes for either deficiencies or over-expression of their gene products.