INTRODUCTIONWilliams syndrome (WS) is a rare but well recognised neurodevelopmental disease affecting the connective tissue and the central nervous system. Many patients are identified through the presence of dysmorphic features and associated cardiac abnormalities. Klinefelter syndrome (KS) is associated with gynaecomastia, small testes, azoospermia and elevated gonadotropin levels. They are recognised in the second decade of life by their tall stature and delay in pubertal development. A combination of constitutive WS and KS has yet to be described.

CLINICAL PICTUREWe report a child with these genetic aberrations, highlighting the clinical characteristics of such an individual.

CONCLUSIONThe manifestations and interactions of both conditions are also discussed.

Body Height ; Body Weight ; Child, Preschool ; Comorbidity ; Humans ; In Situ Hybridization, Fluorescence ; Klinefelter Syndrome ; diagnosis ; epidemiology ; Male ; Williams Syndrome ; diagnosis ; epidemiology

INTRODUCTIONWe report the fi rst successful preimplantation genetic diagnosis (PGD) for Hb Bart's hydrops fetalis in Singapore, involving both fresh and frozen embryo replacement cycles.

CLINICAL PICTURETwo couples who were carriers of the Southeast Asian type double gene deletion (--(SEA) deletion carriers) requested for PGD. Couple A had 2 previous affected pregnancies, while couple B have a child of unknown genotypic status.

TREATMENTOne PGD cycle was performed for each couple. The --(SEA) deletion was detected using a gap-PCR strategy. Couple A had 1 fresh-embryo replacement cycle while couple B underwent 2 frozen-embryo replacement cycles.

OUTCOMECouple A achieved a twin pregnancy. Second trimester complications resulted in premature delivery, where 1 baby girl survived. Couple B achieved a singleton pregnancy resulting in delivery of a healthy baby boy. Genotype analysis of all babies confirmed the PGD results consistent with clinically unaffected status.

CONCLUSIONSWe have successfully performed PGD to avoid Hb Bart's hydrops fetalis syndrome.

Adult ; Embryo Transfer ; Female ; Genetic Carrier Screening ; Genetic Testing ; Hemoglobins, Abnormal ; Humans ; Hydrops Fetalis ; diagnosis ; genetics ; prevention & control ; Male ; Minisatellite Repeats ; genetics ; Ovulation Induction ; methods ; Polymerase Chain Reaction ; Pregnancy ; Pregnancy Complications, Hematologic ; diagnosis ; genetics ; prevention & control ; Preimplantation Diagnosis ; Singapore ; Sperm Injections, Intracytoplasmic ; alpha-Globins ; genetics

INTRODUCTIONWe report on the first successful preimplantation genetic diagnosis (PGD) in Singapore.

CLINICAL PICTUREA couple who are beta-thalassaemia carriers and have an affected daughter requested for PGD.

TREATMENTTwo cycles of PGD were performed on the couple. Beta-thalassaemia mutations were detected using a nested PCR and minisequencing strategy, and unaffected embryos were selected for transfer.

OUTCOMEA singleton pregnancy was achieved in the second PGD cycle, resulting in the birth of a healthy baby boy with carrier genotype.

CONCLUSIONSThis case report documents the first successful PGD in Singapore, involving a couple at-risk of transmitting beta-thalassaemia major.

Adult ; Female ; Fertilization in Vitro ; Humans ; Male ; Pregnancy ; Preimplantation Diagnosis ; Risk Factors ; Singapore ; beta-Thalassemia ; diagnosis ; genetics ; prevention & control

INTRODUCTIONExtracorporeal membrane oxygenation (ECMO) is a cardiopulmonary bypass technique (CPB) which provides life-saving support in patients with refractory cardiorespiratory failure until cardiopulmonary recovery or organ replacement.

MATERIALS AND METHODSThis is a single centre retrospective study reporting the largest series of paediatric patients in Singapore who received ECMO support over an 11-year period from January 2002 to December 2012. The objective is to describe the characteristics of the patients and to report the survival to hospital discharge, complications during ECMO and other long-term complications.

RESULTSForty-eight patients received ECMO during the study period. ECMO was initiated for myocarditis in majority of the paediatric patients whereas postoperative low cardiac output state was the most common indication in the neonatal population. The overall survival rate to hospital discharge was 45.8%. Survival was highest in the neonates with respiratory failure (75%). Haematological and cardiac complications were most common during ECMO. Age group, gender, duration of ECMO, need for renal replacement therapy, acute neurological complications were not associated with mortality. Those needing inotropic support during ECMO had poorer survival while those with hypertension requiring vasodilator treatment had a higher survival rate. The survival rates for ECMO patients more than doubled from the initial 6 years of 23% to 54% in the last 5 years of the study period. Long-term complications encountered included neurological, respiratory and cardiac problems.

CONCLUSIONECMO is a life-saving modality for neonatal and paediatric patients with cardiopulmonary failure from diverse causes. Patients with persistent need for inotropes during ECMO had poorer outcome. Centre experience had an impact on ECMO outcome.

Adolescent ; Child ; Child, Preschool ; Extracorporeal Membrane Oxygenation ; adverse effects ; Female ; Heart Failure ; therapy ; Humans ; Infant ; Infant, Newborn ; Male ; Patient Discharge ; Respiratory Insufficiency ; mortality ; therapy ; Retrospective Studies ; Survival Rate ; Tertiary Care Centers ; Young Adult

OBJECTIVETo examine the Eastern-Western difference in the interpretation of Integrative Medicine Attitude Questionnaire (IMAQ) by assessing the psychometric properties of a revised Chinese medicine (CM)-specific version of IMAQ (CM-IMAQ).

METHODSFactor and Rasch analysis were performed with data collected from a mail survey of 165 Hong Kong Western medical doctors (WMD) randomly sampled from the official registry. The structural validity, unidimensionality, item fit, and differential item functioning (DIF) of the Hong Kong CM-IMAQ were evaluated.

RESULTSConfirmatory factor analysis (CFA) demonstrated that the original IMAQ factor structure was not concordant with our data on Chinese WMD, and subsequent explanatory factor analysis (EFA) validated a new three-factor model for CM-IMAQ: (1) attitude towards "tonification", (2) attitude towards the effectiveness of CM, and (3) attitude towards CM knowledge. The original IMAQ factor on holism and doctor-patient relationship disappeared. Rasch analysis confirmed the unidimensionality of "tonification" and the effectiveness domains, but further refinement of the knowledge domain is needed.

CONCLUSIONSCultural adaptation of the IMAQ has demonstrated differences between Eastern and Western doctors trained in allopathic medicine in their interpretations of holism in healthcare. For Chinese WMD, the emphasis of holistic care is placed on "tonifying" the body rather than on nurturing the mind and spirit. Confucian and Taoist conceptualizations of mental health as well as the persistent stigma towards mental illness within modern Chinese culture may explain why Chinese WMD do not regard mental health promotion as part of routine healthcare.

Aged ; Attitude of Health Personnel ; Emotions ; Factor Analysis, Statistical ; Female ; Holistic Health ; statistics & numerical data ; Hong Kong ; epidemiology ; Humans ; Integrative Medicine ; statistics & numerical data ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Surveys and Questionnaires

INTRODUCTIONWe aimed to develop and implement a short tandem repeat (STR) polymerase chain reaction alternative to fluorescence in situ hybridisation (FISH) for the preimplantation genetic diagnosis (PGD) of chromosomal translocations.

METHODSSelected informative STRs located on translocated arms of relevant chromosomes were used to discriminate between normal and unbalanced chromosome states in each embryo.

RESULTSPGD cycles were performed on five couples where one spouse carried a balanced translocation. 27 embryos were analysed, of which 12 were normal/balanced, 12 were abnormal/unbalanced and three were indeterminate. Four PGD cycles proceeded to embryo transfer, of which two led to pregnancy. The first pregnancy showed a normal male karyotype, and a healthy baby was delivered at term. A second pregnancy unexpectedly miscarried in the second trimester from unknown causes.

CONCLUSIONSTR analysis is a simple and suitable alternative to FISH for detecting unbalanced chromosomal states in preimplantation embryos.

Female ; Fertilization in Vitro ; Humans ; Male ; Microsatellite Repeats ; genetics ; Polymerase Chain Reaction ; methods ; Polymorphism, Genetic ; genetics ; Pregnancy ; Pregnancy Outcome ; Preimplantation Diagnosis ; methods ; Translocation, Genetic ; genetics

BACKGROUNDThe receptor tyrosine kinase-like orphan receptor 2 (ROR2) gene has been recently shown to play important roles in palatal development in animal models and resides in the chromosomal region linked to non syndromic cleft lip with or without cleft palate in humans. The aim of this study was to investigate the possible association between ROR2 gene and non-syndromic oral clefts.

METHODSHere we tested 38 eligible single-nucleotide polymorphisms (SNPs) in ROR2 gene in 297 non-syndromic cleft lip with or without cleft palate and in 82 non-syndromic cleft palate case parent trios recruited from Asia and Maryland. Family Based Association Test was used to test for deviation from Mendelian inheritance. Plink software was used to test potential parent of origin effect. Possible maternally mediated in utero effects were assessed using the TRIad Multi-Marker approach under an assumption of mating symmetry in the population.

RESULTSSignificant evidence of linkage and association was shown for 3 SNPs (rs7858435, rs10820914 and rs3905385) among 57 Asian non-syndromic cleft palate trios in Family Based Association Tests. P values for these 3 SNPs equaled to 0.000068, 0.000115 and 0.000464 respectively which were all less than the significance level (0.05/38 = 0.0013) adjusted by strict Bonferroni correction. Relevant odds ratios for the risk allele were 3.42 (1.80 - 6.50), 3.45 (1.75 - 6.67) and 2.94 (1.56 - 5.56), respectively. Statistical evidence of linkage and association was not shown for study groups other than non-syndromic cleft palate. Neither evidence for parent-of-origin nor maternal genotypic effect was shown for any of the ROR2 markers in our analysis for all study groups.

CONCLUSIONOur results provided evidence of linkage and association between the ROR2 gene and a gene controlling risk to non-syndromic cleft palate.

Asian Continental Ancestry Group ; genetics ; Cleft Lip ; genetics ; Cleft Palate ; genetics ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Linkage Disequilibrium ; genetics ; Polymorphism, Single Nucleotide ; genetics ; Receptor Tyrosine Kinase-like Orphan Receptors ; genetics