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.

Williams syndrome and the elastin gene in Thai patients.

Williams syndrome (WS) has long been known as a complex disorder of dysmorphic facial features, described as elfin face, mental retardation or learning disability, loquacious personality, and supravalvular aortic stenosis. The etiology is now known to be due to deletion of the elastin gene (ELN) on long arm of chromosome 7. Thai patients were previously reported by clinical diagnosis. This study reports the first two cases of WS with ELN deletion diagnosed by fluorescent in situ hybridization (FISH) technique. Clinically, hyperacusis is a common finding in WS associated with otitis media. Neither of the patients had hyperacusis, but one of them had bilateral sensorineural hearing loss, which to our knowledge, has never been reported.

Chromosome 22q11 deletion syndrome: the first three cases reported in Thailand.

The DiGeorge, velocardiofacial, and conotruncal anomaly face syndromes were originally described as separate disorders due to different concerns regarding phenotypes. However, all these disorders have some common clinical manifestations, including congenital heart defect, facial anomaly, and developmental delay. It is now clear that most cases of these syndromes have a common cause resulting from microdeletion of chromosome 22q11. This study reports the first three cases of Thai children presented with developmental delays. All are females who were known cases of congenital heart diseases. Their minor facial anomalies were subtle and not previously recognized as of any syndromes. The chromosome study by fluorescent in situ hybridization technique yielded microdeletion of chromosome 22q11. Without known prevalence in Asian populations, except in Japanese children, further study for chromosome 22q11 deletion syndrome in Asian children with conotruncal heart defects, who also have minor facial anomalies or developmental delays, should be undertaken.

Histiocytoses in children: analysis of 120 cases and the bone marrow findings in infection-induced hemophagocytic syndrome vs malignant histiocytosis.

Retrospective analysis of childhood histiocytoses treated at the Department of Pediatrics, Ramathibodi Hospital from May 1970 till June 30, 1992 to verify the prevalence according to the recent classification, course and prognosis was conducted. Among 120 cases, 54 were Class I or Langerhan Cell Histiocytosis (LCH, previously called Histiocytosis-X). Nineteen cases were Class II: Infection-Associated Hemophagocytic Syndrome (IAHS) and Sinus Histiocytosis. Forty-seven cases were class III which included acute monocytic leukemia, juvenile CML; malignant histiocytosis, HMR, and histiocytic lymphoma. Excellent prognosis (cure) was seen in all cases of Hand-Schuller Christian Disease, eosinophilic granuloma, sinus histiocytosis with massive lymphadenopathy and many cases of Class II (except IAHS). The worse prognosis (100% mortality rate) was seen in HMR and juvenile CML. The intermediate prognosis (50%, 54%, 58.8% and 66.7% mortality rate) was seen in MH, HL, LSD and IAHS respectively. To differentiate between IAHS and MH/HMR, the prominent bone marrow findings in 12 cases of IAHS revealed that every case showed prominent hemophagocytosis by the promono-histiocytes/histiocytes, the maximal total erythroblasts (TE) were only 7.5 per cent except for 3 cases; in which one case with agranulocytosis from co-trimoxazole had 84 per cent erythroid cells, one case with prior co-trimoxazole treatment had 37 per cent TE, the last one had 40 per cent TE with massive GI bleeding while in the recovery stage of DHF. All 5 cases of HMR had prominent hemophagocytosis and increased TE (> 22%).(ABSTRACT TRUNCATED AT 250 WORDS)