A clinical checklist for fragile X syndrome: screening of Thai boys with developmental delay of unknown cause.

The aim of this study was to determine a cost-effective clinical checklist for fragile X syndrome (FXS) screening in a Thai male pediatric population with developmental delay of unknown cause. We studied 179 non-FXS male patients and 27 FXS patients from 18 families (age < or = 15 years). A six-item clinical checklist was used including family history (FH), long and narrow face (F), prominent and large ears (E), attention deficit/hyperactivity (AH), autistic-like behavior (AT) and testicular volume (T). These were scored as 0 if absent, 1 if borderline, and 2 if present. All patients were tested by using PCR and/or southern blot for the FMR1 gene. We used a logistic regression model from a computer program to analyze the data (Stata, version 5.0). We used logistic regression with cluster in the same family (average score) to eliminate bias from the related FXS cases. We found that a five-item checklist, 2FH + F + 0.5E + 2AH + T = total score, was the best model. When we used this clinical checklist with a threshold of total score of 4, 78.7 per cent of the screened cases with total scores < or = 4 could be eliminated as negative cases. In addition, all positive FXS cases had total scores > 4. We propose this five-item model for FXS screening in clinical pediatric practice, particularly from Asian population settings.

Prevalence and clinical characteristics of fragile X syndrome at child development clinic, Ramathibodi Hospital.

Fragile X syndrome, the most common cause of inherited mental retardation, is an X-linked genetic disorder caused by an expanded CGG repeat in the fragile X mental retardation 1 gene. It is characterized by mental retardation, behavioral features, and physical features, such as a long face with large protruding ears and macro-orchidism. A screening for the syndrome was conducted in a representative sample of pediatric patients, who had developmental delay or mental retardation with unknown cause, at the Child Development Clinic, Ramathibodi Hospital. The DNA test was performed on all patients using PCR and southern blot techniques. Five positive cases were detected from 114 screened subjects, and more four cases confirmed among other family members. Two of five positive families initially denied a family history of mental retardation. Among 9 cases of fragile X syndrome, four had hyperactivity and two had autistic like behavior. More than half had rather a long face or prominent ears. Three boys had macro-orchidism.

Molecular screening for fragile X syndrome in Thailand.

Fragile X syndrome (FXS) is the most common form of inherited mental retardation. We screened for FXS in 237 Thai males (age < or = 15 years) with developmental delay of unknown cause. We found 16 (6.8%) to have FXS using standard molecular analysis. Wc then studied the extended families of these 16 FXS subjects and 4 other independently ascertained FXS cases. We found that there were at least 35 affected males and 8 affected females. In addition we found that there were at least 31 premutation carrier females and 4 premutation males. The CGG repeats numbers in these premutation individuals ranged from 60 to 125. By comparison, the normal CGG repeats were 19-50 with a heterozygosity of 67.2% in 337 randomly selected males. This study providcs insight into the high incidence of FXS in developmentally delayed Thai males and points the way toward the means of prevention of mental retardation by genetic counseling and prenatal diagnosis.

The frequency of fragile X syndrome among selected patients at Songklanagarind Hospital during 1991-1996, studied by cytogenetic and molecular methods.

Fragile X syndrome is the most common inherited form of mental disability, world-wide. Main clinical features are cognitive deficit, speech difficulties, delayed development, autism, and particular physical characteristics. The syndrome can be cytogenetically diagnosed by the expression of chromosome X fragile site at band Xq27.3. At molecular level, the cause of the syndrome is defined as an abnormal expansion of CGG trinucleotide repeats in the 5'UTR of the FMR-1 gene as well as hypermethylation at the proximal CpG island. Study of fragile X syndrome at Songklanagarind Hospital during May 1991-June 1996 was herein reported. A total of 287 blood samples of 260 unrelated families were cytogenetically examined by using lymphocyte culture method with 2-4 different treatments. Frequency of positive fragile X cases was found to be 7 in 260 (2.7%). Among relatives of the positive ones, 13 individuals were also positive. Other types of chromosome abnormalities were detected in 13 cases (5%). For molecular study, DNA samples were obtained from 97 cases. Investigation of CGG repeat expansion was performed by PCR method. Abnormal expansion was identified as full mutation (> 200 repeats) and premutation (> 50-200 repeats). The abnormalities were found in 14 individuals of 5 unrelated cases; 6 with full mutation and 8 with premutation. No molecular study on the two cytogenetic positive cases has been performed. In conclusion, a total of 50 individuals with fragile X abnormality has been documented: 18 affected cases and 32 carriers. Investigation of the remaining suspected members in positive families is in progress. The information and experience will lead to prevention of this genetic disease by prenatal diagnosis and elective abortion in Thailand.