Predictive and pre-natal testing for Huntington's Disease (HD) has been available since 1987. Initially this was offered by linkage analysis, which was surpassed by the advent of the direct mutation test for HD in 1993. Direct mutation analysis provided an accurate test that not only enhanced predictive and pre-natal testing, but also permitted the diagnostic testing of symptomatic individuals. The objective of this study was to investigate the uptake, utilization, and outcome of predictive, pre-natal and diagnostic testing in Canada from 1987 to April 1, 2000. A retrospective design was used; all Canadian medical genetics centres and their affiliated laboratories offering genetic testing for HD were invited to participate. A total of 15 of 22 centres (68.2%), currently offering or ever having offered genetic testing for HD, responded, providing data on test results, demographics, and clinical history. A total of 1061 predictive tests, 15 pre-natal tests, and 626 diagnostic tests were performed. The uptake for predictive testing was approximately 18% of the estimated at-risk Canadian population, ranging from 12.5% in the Maritimes to 20.7% in British Columbia. There appears to have been a decline in the rate of testing in recent years. Of the predictive tests, 45.0% of individuals were found to have an increased risk, and a preponderance of females (60.2%) sought testing. A greater proportion of those at < or = 25% risk sought predictive testing once direct CAG mutation analysis had become available (10.9% after mutation analysis vs 4.7% before mutation analysis, p = 0.0077). Very few pre-natal tests were requested. Of the 15 pre-natal tests, 12 had an increased risk, resulting in termination of pregnancy in all but one. Diagnostic testing identified 68.5% of individuals to be positive by mutation analysis, while 31.5% of those with HD-like symptoms were not found to have the HD mutation. The positive diagnostic tests included 24.5% of individuals with no known prior family history of HD.

An 8-year-old boy with partial trisomy 14q and phenotype distinct from previously reported cases is described. The mother carries a balanced 9;14 reciprocal translocation. The patient presented with minor facial anomalies, developmental delay, hyperphagia, and obesity. Imprinting of maternal chromosome 14 or disruption of one or more genes on chromosome 9 may be responsible for our patient's manifestations.

A 7-year old female with global cognitive impairment, short attention span, hyperactivity, impulsivity, and many compulsive behaviors was referred to the Genetics Clinic. Height was below the 5th centile and weight was at the 5th centile while head circumference was at the 50th centile. Minor anomalies included bluish sclera, low set and slightly posteriorly rotated auricles and a narrow palate with marked overbite. There was no significant family history. Chromosome analysis showed an unbalanced, mosaic female karyotype consisting of three cell lines: 46,X,+r[46]/45,X[37]/45,X,dup(1)(q11q21.3) [17] de novo.ish r(X)(DXZ1+,XIST+). Expression of XIST was observed in cDNA from the patient, suggesting the presence of an inactive X chromosome. Inactivation was confirmed by detection of a methylated allele of androgen receptor. This methylated allele was under-represented in undigested DNA, consistent with it arising from the r(X) which was present in only a minority of the patient's cells. The clinical phenotype of the tiny r(X) syndrome in our patient is obviously further influenced by mosaicism for the dup(1). Few cases of duplication of the proximal portion of chromosome 1 have been reported. Of these, the duplication either was present in all cells or involved different band regions so that a direct comparison would be difficult. However, the lower percentage of mosaicism for the dup(1) in our patient would suggest a milder influence on the clinical phenotype.