Common Clinical Characteristics and Rare Medical Problems of Fragile X Syndrome in Thai Patients and Review of the Literature

Background. Clinical characteristics of fragile X syndrome (FXS) have been well documented in Caucasians, whereas in Asians they have rarely been described. Those that have been conducted used small cohorts that utilized DNA for diagnosis and larger cohorts that utilized cytogenetics for diagnosis. This study is to describe clinical characteristics of FXS in a large cohort of Thai patients diagnosed by standard molecular methods. Methods. Seventy-seven index cases and 46 affected relatives diagnosed with FXS were recruited into the study. To determine frequencies of common characteristics of FXS in prepubertal boys, we reviewed 56 unrelated cases aged between 18 and 146 months. To list rare medical problems, we reviewed 75 cases aged between 8 months to 71 years old, including 53 index cases and 22 affected relatives. In addition, we selected 16 clinical studies from various ethnicities for comparison with our findings. Results. In prepubertal boys with FXS, attention deficit and/or hyperactivity, prominent ears, macroorchidism, and elongated face were observed in 96%, 80%, 53%, and 48% of patients, respectively, whereas recognizable X-linked inheritance presented in 11% of patients. IQ scores ranged between 30 and 64 (mean ± SD = 43±9, n=25). We observed clinical findings that rarely or have never been reported, for example, medulloblastoma and tetralogy of Fallot. Conclusion. Attention deficit and/or hyperactivity and prominent ear are the most common behavioral and physical features in prepubertal boys with FXS, respectively. There are differences in frequencies of clinical characteristics observed between ethnicities; however, it is difficult to draw a solid conclusion due to different recruitment criteria and sample sizes within each study

Body-Fat-Percentile Curves for Thai Children and Adolescents

This study aimed to generate sex-specific percentile curves for the percentage of body fat (PBF) in Thai children using a bioelectrical impedance analysis (BIA). The secondary objective of this study was to determine the association between body fat and other anthropometric measurements. A cross-sectional study was conducted on 3455 Thai school children aged 6–18 years. The body-fat contents were measured using BIA. Smoothed percentile curves of PBF were derived using a scatter plot with a smooth curve fitted by the Loess method. The correlations between the body fat and the anthropometric measurements were assessed using the Spearman’s rank correlation. The 50th and lower body-fat-percentile curves of the boys slowly increased until age 12, after which they slightly decreased until age 15 and then slightly increased until age 18. In the higher boys’ percentiles, the body fat sharply increased until age 11 and then decreased until age 18. In the girls, the PBF percentiles increased steadily from 6 to 18 years. The body-mass index was strongly correlated with PBF and fat mass in both sexes. The waist-to-height ratios showed strong correlations with PBF and fat mass in the boys but were moderate in the girls. The use of PBF percentile curves can be an additional metric for the evaluation of obesity in Thai children

Vitamin D status in non-pregnant women of reproductive age: a study in Southern Thailand

Abstract Vitamin D inadequacy is a global problem in all age groups. Although there are various studies of vitamin D status in pregnant women in Southeast Asia, to date there are few studies from Southeast Asia examining vitamin D status in non-pregnant women of reproductive age. To examine the prevalence of vitamin D insufficiency (VDI) in healthy non-pregnant women of reproductive age in Southern Thailand, 120 healthy non-pregnant women aged 18–42 years were enrolled. Demographic and lifestyle data relevant to vitamin D assessment (sunlight exposure, nutritional intake, type of dress, sunscreen use) and biochemical studies (serum 25-hydroxyvitamin D or 25OHD, parathyroid hormone, calcium, phosphate) were obtained. VDI was classified as serum 25OHD < 20 ng/mL. The average serum 25OHD level was 23.1 ± 6.0 ng/mL. The overall prevalence of VDI was 34.1%. The average dietary intake of calcium, phosphorus and vitamin D and the average duration of sunlight exposure per week were not significantly different between the VDI women and the vitamin D sufficient (VDS) women. Logistic regression analysis found that the significant risk factors for VDI were greater body mass index and higher family income (p-values 0.01 and 0.02, respectively). The prevalence of VDI in non-pregnant women was high at 34%. As the dietary sources of vitamin D are limited and cutaneous vitamin D synthesis is limited by avoidance of sunlight exposure, vitamin D fortification in common daily foods would be an alternative option to reach the recommended vitamin D intake generally of at least 800 IU/day

Table3_Case report: Molecular analysis of a 47,XY,+21/46,XX chimera using SNP microarray and review of literature.DOCX

Chimerism is a very rare genetic finding in human. Most reported cases have a chi 46,XX/46,XY karyotype. Only three non-twin cases carrying both trisomy 21 and a normal karyotype have been reported, including two cases with a chi 47,XY,+21/46,XX karyotype and a case with a chi 47,XX,+21/46,XY karyotype. Herein we describe an additional case with a chi 47,XY,+21/46,XX karyotype. For the case, a physical examination at the age of 1 year revealed ambiguous genitalia with no features of Down syndrome or other malformations. Growth and developmental milestones were within normal ranges. We performed short tandem repeat (STR) and single nucleotide polymorphism (SNP) microarray analyses to attempt to identify the mechanism underlying the chimerism in this patient and the origin of the extra chromosome 21. Cytogenetic analyses of the patient’s peripheral blood revealed approximately 17% of a 47,XY,+21 lineage by G-banding karyotype analysis, 13%–17% by FISH analyses of uncultured peripheral blood, and 10%–15% by SNP microarray analysis. Four years later, the percentage of trisomy 21 cells had decreased to approximately 6%. SNP microarray and STR analyses revealed a single maternal and double paternal genetic contribution to the patient for the majority of the markers, including the chromosome 21 markers. The extra chromosome 21 was paternally derived and meiosis I nondisjunction likely occurred during spermatogenesis. The mechanisms underlying chimera in our case was likely fertilization two spermatozoa, one with an ovum and the other with the second polar body.</p

Table1_Case report: Molecular analysis of a 47,XY,+21/46,XX chimera using SNP microarray and review of literature.DOCX

Chimerism is a very rare genetic finding in human. Most reported cases have a chi 46,XX/46,XY karyotype. Only three non-twin cases carrying both trisomy 21 and a normal karyotype have been reported, including two cases with a chi 47,XY,+21/46,XX karyotype and a case with a chi 47,XX,+21/46,XY karyotype. Herein we describe an additional case with a chi 47,XY,+21/46,XX karyotype. For the case, a physical examination at the age of 1 year revealed ambiguous genitalia with no features of Down syndrome or other malformations. Growth and developmental milestones were within normal ranges. We performed short tandem repeat (STR) and single nucleotide polymorphism (SNP) microarray analyses to attempt to identify the mechanism underlying the chimerism in this patient and the origin of the extra chromosome 21. Cytogenetic analyses of the patient’s peripheral blood revealed approximately 17% of a 47,XY,+21 lineage by G-banding karyotype analysis, 13%–17% by FISH analyses of uncultured peripheral blood, and 10%–15% by SNP microarray analysis. Four years later, the percentage of trisomy 21 cells had decreased to approximately 6%. SNP microarray and STR analyses revealed a single maternal and double paternal genetic contribution to the patient for the majority of the markers, including the chromosome 21 markers. The extra chromosome 21 was paternally derived and meiosis I nondisjunction likely occurred during spermatogenesis. The mechanisms underlying chimera in our case was likely fertilization two spermatozoa, one with an ovum and the other with the second polar body.</p

Presentation1_Case report: Molecular analysis of a 47,XY,+21/46,XX chimera using SNP microarray and review of literature.pptx

Chimerism is a very rare genetic finding in human. Most reported cases have a chi 46,XX/46,XY karyotype. Only three non-twin cases carrying both trisomy 21 and a normal karyotype have been reported, including two cases with a chi 47,XY,+21/46,XX karyotype and a case with a chi 47,XX,+21/46,XY karyotype. Herein we describe an additional case with a chi 47,XY,+21/46,XX karyotype. For the case, a physical examination at the age of 1 year revealed ambiguous genitalia with no features of Down syndrome or other malformations. Growth and developmental milestones were within normal ranges. We performed short tandem repeat (STR) and single nucleotide polymorphism (SNP) microarray analyses to attempt to identify the mechanism underlying the chimerism in this patient and the origin of the extra chromosome 21. Cytogenetic analyses of the patient’s peripheral blood revealed approximately 17% of a 47,XY,+21 lineage by G-banding karyotype analysis, 13%–17% by FISH analyses of uncultured peripheral blood, and 10%–15% by SNP microarray analysis. Four years later, the percentage of trisomy 21 cells had decreased to approximately 6%. SNP microarray and STR analyses revealed a single maternal and double paternal genetic contribution to the patient for the majority of the markers, including the chromosome 21 markers. The extra chromosome 21 was paternally derived and meiosis I nondisjunction likely occurred during spermatogenesis. The mechanisms underlying chimera in our case was likely fertilization two spermatozoa, one with an ovum and the other with the second polar body.</p

Table2_Case report: Molecular analysis of a 47,XY,+21/46,XX chimera using SNP microarray and review of literature.DOCX

Chimerism is a very rare genetic finding in human. Most reported cases have a chi 46,XX/46,XY karyotype. Only three non-twin cases carrying both trisomy 21 and a normal karyotype have been reported, including two cases with a chi 47,XY,+21/46,XX karyotype and a case with a chi 47,XX,+21/46,XY karyotype. Herein we describe an additional case with a chi 47,XY,+21/46,XX karyotype. For the case, a physical examination at the age of 1 year revealed ambiguous genitalia with no features of Down syndrome or other malformations. Growth and developmental milestones were within normal ranges. We performed short tandem repeat (STR) and single nucleotide polymorphism (SNP) microarray analyses to attempt to identify the mechanism underlying the chimerism in this patient and the origin of the extra chromosome 21. Cytogenetic analyses of the patient’s peripheral blood revealed approximately 17% of a 47,XY,+21 lineage by G-banding karyotype analysis, 13%–17% by FISH analyses of uncultured peripheral blood, and 10%–15% by SNP microarray analysis. Four years later, the percentage of trisomy 21 cells had decreased to approximately 6%. SNP microarray and STR analyses revealed a single maternal and double paternal genetic contribution to the patient for the majority of the markers, including the chromosome 21 markers. The extra chromosome 21 was paternally derived and meiosis I nondisjunction likely occurred during spermatogenesis. The mechanisms underlying chimera in our case was likely fertilization two spermatozoa, one with an ovum and the other with the second polar body.</p

Table4_Case report: Molecular analysis of a 47,XY,+21/46,XX chimera using SNP microarray and review of literature.DOCX

Chimerism is a very rare genetic finding in human. Most reported cases have a chi 46,XX/46,XY karyotype. Only three non-twin cases carrying both trisomy 21 and a normal karyotype have been reported, including two cases with a chi 47,XY,+21/46,XX karyotype and a case with a chi 47,XX,+21/46,XY karyotype. Herein we describe an additional case with a chi 47,XY,+21/46,XX karyotype. For the case, a physical examination at the age of 1 year revealed ambiguous genitalia with no features of Down syndrome or other malformations. Growth and developmental milestones were within normal ranges. We performed short tandem repeat (STR) and single nucleotide polymorphism (SNP) microarray analyses to attempt to identify the mechanism underlying the chimerism in this patient and the origin of the extra chromosome 21. Cytogenetic analyses of the patient’s peripheral blood revealed approximately 17% of a 47,XY,+21 lineage by G-banding karyotype analysis, 13%–17% by FISH analyses of uncultured peripheral blood, and 10%–15% by SNP microarray analysis. Four years later, the percentage of trisomy 21 cells had decreased to approximately 6%. SNP microarray and STR analyses revealed a single maternal and double paternal genetic contribution to the patient for the majority of the markers, including the chromosome 21 markers. The extra chromosome 21 was paternally derived and meiosis I nondisjunction likely occurred during spermatogenesis. The mechanisms underlying chimera in our case was likely fertilization two spermatozoa, one with an ovum and the other with the second polar body.</p