Displaying publications 1 - 20 of 77 in total

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  1. Fulltext Birth defects registries in the genomics era: challenges and opportunities for developing countries
    Thong MK
    Front Pediatr, 2014;2:60.
    PMID: 24982853 DOI: 10.3389/fped.2014.00060
    Birth defects or congenital anomalies are one of the major causes of disability in developed and developing countries. Data on birth defects from population-based studies originating from developing countries are lacking. Increasingly, there is a shift to genetic testing and genomics study of birth defects. However, the translation from bench findings to bedside medicine has been muted. There is a need to address this imbalance where congenital anomalies remained the top etiology for neonatal mortality in developing countries. To build capacity in low resource countries, there is a need for accurate collection and ascertainment of birth defects in developing countries. The systematic collection and analysis of data on major birth defects using birth defects registries (BDRs) are an integral part of all clinical genetic services. Healthcare planners in developing countries must be aware of the advantages and limitations of BDRs. Despite the advent of the genomics era, BDRs are essential to the planning and developing care and prevention services at local and national levels, particularly in low resource or developing countries.
  2. A tribute to Keiko Kobayashi and her work on citrin deficiency
    Thong MK
    Mol Genet Metab, 2012 Apr;105(4):551-2.
    PMID: 22284267 DOI: 10.1016/j.ymgme.2012.01.003
  3. Fulltext Genes, medicine and society: from paediatrics to genetic counselling and beyond
    Thong MK
    JUMMEC, 2012;15(2):1-8.
    MyJurnal
    The story of clinical genetics is a relatively new one, first spearheaded by paediatrics but increasingly, has taken root in all branches of medicine leading to ‘personalised medicine’. There are expectations that this revolution in genetics will pave the way to genomic medicine and a cure for all inherited disorders. The development of the field of Clinical Genetics and genetic counselling in Malaysia is still in its infancy. Using evidence-based data on genetic disorders such as birth defects, inborn errors of metabolism, genetic syndromes, neurological disorders and hereditary cancers, that hitherto have not been well documented in Malaysia, this review article will focus on findings and issues that will present a unique insight and opportunity to understanding the complex genetic counselling issues related to clinical genetics in Malaysia.
  4. Achieving the targets of sustainable development goals (2030 agenda) for congenital disorders in Asia: Bottlenecks and interventions
    Thong MK
    Am J Med Genet C Semin Med Genet, 2019 06;181(2):254-261.
    PMID: 30801969 DOI: 10.1002/ajmg.c.31690
    The United Nations General Assembly adopted the 2030 Agenda for Sustainable Development in November 2015 which included a set of 17 measurable "sustainable development goals" (SDGs). The SDGs included targets to end preventable deaths of newborns and children under 5 years of age by 2030, universal health care coverage, reduction of premature mortality from noncommunicable diseases (NCDs) by 33% as well as support the development and research for medicines for both communicable and NCDs. Although some successes were achieved in combating communicable diseases and improved childhood mortality rates, health systems in Asia are generally characterized by lack of accurate epidemiological information on congenital disorders, lack of human and financial resources, and inadequate focus on public health strategies to ensure targeted interventions, low level knowledge on congenital disorders amongst the community and healthcare providers and the ethical dilemma of managing rare congenital disorders in an environment of low national health expenditures. These bottlenecks must be addressed systematically and interventions such as the use of innovative epidemiological tools to overcome lack of data, increased efforts to standardize rare disease nomenclature and classification and renewed interest in birth defects registries by countries in the region must be considered. Targeted curative and public health approaches currently used in thalassaemia and neural tube defects may be used for other congenital disorders in Asian countries. The implementation of congenital disorders-related research, prevention, care, and treatment delivery services must be integrated into existing health systems in order to be effective to achieve the targets of SDG2030.
  5. Fulltext Single mitochondrial DNA deletions in chronic progressive external ophthalmoplegia (CPEO) and Kearns-Sayre syndrome (KSS) patients from a multiethnic Asian population
    Chong, Jia-Woei, Azlina Ahmad Annuar, Wong, Kum-Thong, Thong, Meow-Keong, Goh, Khean-Jin
    Neurology Asia, 2014;19(1):27-36.
    MyJurnal
    Mitochondrial DNA (mtDNA) deletions are a major cause of chronic progressive external ophthalmoplegia (CPEO) and Kearns-Sayre syndrome (KSS). We analyzed single mtDNA deletions in 11 CPEO and one KSS patients by means of Southern blot and long polymerase chain reaction (PCR) assays. The deletion sizes ranged from 3.4 kb to 6.9 kb whereas the heteroplasmy level varied from 18.8% to 85.5%. Two unique deletions sized 4320 bp and 4717 bp were found. This study represents the first genetic screen of mtDNA disorders in Malaysia, and it follows the data seen in other published reports on CPEO and KSS genetic aetiology.
  6. Genetic counseling services and development of training programs in Malaysia
    Lee JM, Thong MK
    J Genet Couns, 2013 Dec;22(6):911-6.
    PMID: 23615969 DOI: 10.1007/s10897-013-9589-z
    Genetic counseling service is urgently required in developing countries. In Malaysia, the first medical genetic service was introduced in 1994 at one of the main teaching hospitals in Kuala Lumpur. Two decades later, the medical genetic services have improved with the availability of genetic counseling, genetic testing and diagnosis, for both paediatric conditions and adult-onset inherited conditions, at four main centers of medical genetic services in Malaysia. Prenatal diagnosis services and assisted reproductive technologies are available at tertiary centres and private medical facilities. Positive developments include governmental recognition of Clinical Genetics as a subspecialty, increased funding for genetics services, development of medical ethics guidelines, and establishment of support groups. However, the country lacked qualified genetic counselors. Proposals were presented to policy-makers to develop genetic counseling courses. Challenges encountered included limited resources and public awareness, ethical dilemmas such as religious and social issues and inadequate genetic health professionals especially genetic counselors.
  7. β-Thalassemias
    Thong MK, Ngim CF
    N Engl J Med, 2021 Jun 03;384(22):2165.
    PMID: 34077655 DOI: 10.1056/NEJMc2105064
  8. Spectrum of inherited metabolic disorders in Malaysia
    Thong MK, Yunus ZM
    Ann Acad Med Singap, 2008 Dec;37(12 Suppl):66-5.
    PMID: 19904455
    Issues pertaining to the diagnosis and management of inborn errors of metabolism (IEM) in Malaysia included low awareness of atypical and variable presentations in IEMs leading to delayed diagnosis or treatment, absence of reliable population data on IEMs and involvement of multiple siblings in the same family due to consanguinity. The importance of careful family history taking and genetic counselling are emphasised. Selected testing of ill infants and children for IEM yielded a positive 2% (264/13,500) results for IEMs in Malaysia. Out of the 264 patients, the spectrum of IEMs in Malaysia included organic acidurias (98), aminoacidopathies (78), urea cycle defects (54), neurotransmitter conditions (12) and lysosomal disorders, mainly mucopolysaccharidosis (14). Confirmatory studies of IEMs are an important aspect of management of IEMs. There is a need for more metabolic specialists and funding for diagnosis and treatment of IEMs in Malaysia. Long-term care issues and cost-effectiveness of IEM therapy, supportive and preventive aspects will need further studies in Malaysia.
  9. Prenatal detection of birth defects in a Malaysian population: estimation of the influence of termination of pregnancy on birth prevalence in a developing country
    Ho JJ, Thong MK, Nurani NK
    Aust N Z J Obstet Gynaecol, 2006 Feb;46(1):55-7.
    PMID: 16441696
    We studied 253 women with a pregnancy complicated by a birth defect and 506 controls to determine the frequency and type of prenatal tests and the types of defects detected antenatally. Most women had at least one ultrasound examination, but the frequency of other screening tests was low. Only 38 (15%) of defects were detected antenatally (37 by ultrasound). Birth prevalence is unlikely to be affected by pregnancy termination.
  10. Fulltext Case report: The evolving phenotype of ESCO2 spectrum disorder in a 15-year-old Malaysian child
    Tae SK, Ra M, Thong MK
    Front Genet, 2023;14:1286489.
    PMID: 38288163 DOI: 10.3389/fgene.2023.1286489
    ESCO2 spectrum disorder is an autosomal recessive developmental disorder characterized by growth retardation, symmetrical mesomelic limb malformation, and distinctive facies with microcephaly, with a wide phenotypic continuum that ranges from Roberts syndrome (MIM #268300) at the severe end to SC phocomelia (MIM #269000) at the milder end. ESCO2 encodes a 601-amino acid protein belonging to the Eco1/Ctf7 family of acetyltransferases that is involved in the establishment of sister chromatid cohesion, which is essential for accurate chromosome segregation and genomic stability and thus belongs to a group of disorders called "cohesinopathies". We describe a 15-year-old Malaysian female who presented with the characteristic triad of ESCO2 spectrum disorder, with an equivocal chromosomal breakage study and normal karyotyping findings. She was initially suspected to have mosaic Fanconi anemia but whole exome sequencing (WES) showed a likely pathogenic homozygous splice variant c.955 + 2_955+5del in the ESCO2 gene. During the 15-year diagnostic odyssey, she developed type 2 diabetes mellitus, primary ovarian insufficiency, increased optic cup-to-disc ratio with tortuous vessels bilaterally, and an evolving but distinct facial and skin hypopigmentation phenotype. Of note, there was an absence of learning disabilities. Our findings provide further evidence for ESCO2 spectrum disorder in an Asian child and contribute to defining the clinical and radiographic spectrum.
  11. Neural tube defects in Malaysia: data from the Malaysian National Neonatal Registry
    Boo NY, Cheah IG, Thong MK, Malaysian National Neonatal Registry
    J Trop Pediatr, 2013 Oct;59(5):338-42.
    PMID: 23583959 DOI: 10.1093/tropej/fmt026
    This study aimed to determine the prevalence and early outcome of neural tube defects (NTDs) in Malaysia. This prospective study included all neonates with NTDs (spina bifida, anencephaly, encephalocoele) born in 2009 in 32 Malaysian hospitals in the Malaysian National Neonatal Network. The prevalence of NTDs was 0.42 per 1000 live births, being highest among the indigenous people of Sarawak (1.09 per 1000 live births) and lowest among Malaysians of Chinese descent (0.09 per 1000 live births). The most common type of NTDs was anencephaly (0.19 per 1000 live births), followed by spina bifida (0.11 per 1000 live births) and encephalocoele (0.07 per 1000 live births). Majority of the infants with anencephaly (94.5%, n = 51), 45.8% (n = 11) with encephalocoele and 9.5% (n = 4) with spina bifida died. The median duration of hospital stay was 4 (range: 0-161) days.
  12. Diagnosis and management of Duchenne muscular dystrophy in a developing country over a 10-year period
    Thong MK, Bazlin RI, Wong KT
    Dev Med Child Neurol, 2005 Jul;47(7):474-7.
    PMID: 15991868
    Clinical data on Duchenne muscular dystrophy (DMD) are lacking in developing countries. The objective of this study was to delineate the demographic characteristics, investigations, and outcome of 21 Malaysian males diagnosed with DMD over a period of 10 years. Mean age presentation was 3 years 8 months (SD 23mo; range 10 to 84mo), mean duration from first presentation to diagnosis was 3y 7mo (SD 26mo; range 5 to 84) and the mean age for loss of ambulation was 11 years (SD 25mo; range 102 to 168). There was family history of DMD in five of the 21 patients. Muscle biopsy showed confirmatory findings of DMD in the 16 patients tested. Molecular genetic analysis showed dystrophin gene deletions in 11 of these 16 patients. Four and seven of the students stopped schooling and had learning difficulties, respectively; only nine had satisfactory school performances. Eight out of 14 patients evaluated were classified as having severe to total dependency levels on the modified Barthel Index for activities of daily living assessment. DMD is associated with significant medical and social needs for a developing country such as Malaysia. Earlier referral, genetic counselling, and provision of support and rehabilitative services are the main priorities.
  13. Fulltext Characterisation of beta-globin gene mutations in Malaysian children: a strategy for the control of beta-thalassaemia in a developing country
    Thong MK, Tan JA, Tan KL, Yap SF
    J Trop Pediatr, 2005 Dec;51(6):328-33.
    PMID: 15967770 DOI: 10.1093/tropej/fmi052
    beta-thalassaemia major, an autosomal recessive hemoglobinopathy, is one of the most common single gene disorders in multi-racial Malaysia. The control of beta-thalassaemia major requires a multi-disciplinary approach that includes population screening, genetic counselling, prenatal diagnosis and the option of termination of affected pregnancies. To achieve this objective, the molecular characterisation of the spectrum of beta-globin gene mutations in each of the affected ethnic groups is required. We studied 88 consecutive unrelated individuals and their respective families with beta-thalassaemia (74 beta-thalassaemia major, 12 HbE-beta-thalassaemia, 2 with HbE homozygotes) and four individuals with beta-thalassaemia trait that contributed a total 180 alleles for study. Using a 2-step molecular diagnostic strategy consisting of amplification refractory mutation system (ARMS) to identify the 8 most common mutations followed by other DNA-based diagnostic techniques, a total of 177 (98.3 per cent) of the 180 beta-thalassaemia alleles were characterised. One out of 91 (1 per cent) of the Chinese alleles, one out of 46 (2.2 per cent) Malay alleles and one out of two Indian alleles remained unknown. A 100 per cent success rate was achieved in studying the Kadazandusun community in this study. A strategy to identify beta-globin gene mutations in Malaysians with beta-thalassaemia is proposed based on this outcome.
  14. Fulltext Beyond Critical Congenital Heart Disease: Newborn Screening Using Pulse Oximetry for Neonatal Sepsis and Respiratory Diseases in a Middle-Income Country
    Jawin V, Ang HL, Omar A, Thong MK
    PLoS One, 2015;10(9):e0137580.
    PMID: 26360420 DOI: 10.1371/journal.pone.0137580
    Studies on pulse oximetry screening for neonatal sepsis and respiratory disease in a middle-income country are lacking. Newborn screening for critical congenital heart disease (CCHD) using pulse oximetry is an effective and life-saving strategy in developed countries. While most studies have reported false-positive results during CCHD screening, they have not elaborated on the detected disease types. We studied the effectiveness and outcomes of pulse oximetry newborn screening for non-cardiac hypoxemic diseases such as neonatal sepsis, respiratory diseases, and CCHD in a middle-income country.
  15. Ten-year trend in prevalence and outcome of Down syndrome with congenital heart disease in a middle-income country
    Zahari N, Mat Bah MN, A Razak H, Thong MK
    Eur J Pediatr, 2019 Aug;178(8):1267-1274.
    PMID: 31222391 DOI: 10.1007/s00431-019-03403-x
    Limited data are available on the survival of patients with Down syndrome and congenital heart disease (CHD) from middle-income countries. This retrospective cohort study was performed to determine the trends in the prevalence and survival of such patients born from January 2006 to December 2015 in Malaysia. Among 754 patients with Down syndrome, 414 (55%) had CHD, and no significant trend was observed during the 10 years. Of these 414 patients, 30% had lesions that closed spontaneously, 35% underwent surgery/intervention, 9% died before surgery/intervention, and 10% were treated with comfort care. The overall mortality rate was 23%, the median age at death was 7.6 months, and no significant changes occurred over time. The early and late post-surgery/intervention mortality rates were 0.7% and 9.0%, respectively. Most deaths were of non-cardiac causes. The overall 1-, 5-, and 10-year survival rates were 85.5%, 74.6%, and 72.9%, respectively. Patients with severe lesions, persistent pulmonary hypertension of the newborn, atrioventricular septal defect, and pulmonary hypertension had low survival at 1 year of age.Conclusion: The prevalence of CHD in patients with Down syndrome is similar between Malaysia and high-income countries. The lower survival rate is attributed to limited expertise and resources which limit timely surgery. What is Known: • The survival of patients with Down syndrome with congenital heart disease (CHD) has improved in high-income countries. However, little is known about the survival of patients with Down syndrome with CHD from middle-income countries. • In the Caucasian population, atrioventricular septal defect is the most common type of CHD associated with Down syndrome. What is New: • In middle-income countries, the prevalence of CHD is the same as in high-income countries, but with a lower survival rate. • In the Asian population, ventricular septal defect is the most common type of CHD in patients with Down syndrome.
  16. Asia Pacific Society of Human Genetics (APSHG) from conception to 2019: 13 years of collaboration to tackle congenital malformation and genetic disorders in Asia
    Wasant P, Padilla C, Lam S, Thong MK, Lai PS
    Am J Med Genet C Semin Med Genet, 2019 06;181(2):155-165.
    PMID: 31050142 DOI: 10.1002/ajmg.c.31701
    Putting together the reports in this issue that come from a representation of the different countries in Asia presents an opportunity to share the unique story of the Asia Pacific Society of Human Genetics (APSHG), which has provided the authors of many of these articles. This paper, authored by the Past Presidents of the Society, shares glimpses of how medical genetics activities were first organized in the Asia Pacific region and provides interesting corollaries on how under-developed and developing countries in this part of the world had developed a unique network for exchange and sharing of expertise and resources. Although APSHG was formally registered as a Society in Singapore in 2006, the Society has its origins as far back as in the 1990s with members from different countries meeting informally, exchanging ideas, and collaborating. This treatise documents the story of the experiences of the Society and hopes it will provide inspiration on how members of a genetics community can foster and build a thriving environment to promote this field.
  17. Methylmalonic Aciduria: A Treatable Disorder of Which Adult Neurologists Need to Be Aware
    Tan AH, Mah JSY, Thong MK, Lim SY
    Mov Disord Clin Pract, 2015 09 16;3(1):104-105.
    PMID: 30713905 DOI: 10.1002/mdc3.12237
  18. Fulltext Medical genetics in developing countries in the Asia-Pacific region: challenges and opportunities
    Thong MK, See-Toh Y, Hassan J, Ali J
    Genet Med, 2018 10;20(10):1114-1121.
    PMID: 30093710 DOI: 10.1038/s41436-018-0135-0
    Advances in genetic and genomic technology changed health-care services rapidly in low and middle income countries (LMICs) in the Asia-Pacific region. While genetic services were initially focused on population-based disease prevention strategies, they have evolved into clinic-based and therapeutics-oriented service. Many LMICs struggled with these noncommunicable diseases and were unprepared for the needs of a clinical genetic service. The emergence of a middle class population, the lack of regulatory oversight, and weak capacity-building in medical genetics expertise and genetic counseling services led to a range of genetic services of variable quality with minimal ethical oversight. Some of the current shortcomings faced include the lack of awareness of cultural values in genetic health care, the variable stages of socioeconomic development and educational background that led to increased demand and abuse of genetics, the role of women in society and the crisis of gender selection, the lack of preventive and care services for genetic and birth defects, the issues of gene ethics in medicine, and the lack of understanding of some religious controversies. These challenges provide opportunities for both developing and developed nations to work together to reduce the inequalities and to ensure a caring, inclusive, ethical, and cost-effective genetic service in the region.
  19. Fulltext Sandhoff disease in two siblings of a Malaysian family: Description of novel beta hexosaminidase mutations, magnetic resonance imaging, and spectroscopic findings
    Antony CD, Thong MK, Rahmat K, Muridan R
    Neurol India, 2017 3 11;65(Supplement):S98-S100.
    PMID: 28281504 DOI: 10.4103/neuroindia.NI_1121_15
  20. Terminal microdeletion of chromosome 18 in a Malaysian boy characterized with few features of typical 18q- deletion syndrome: a case report
    Ismail A, Ahid F, Thong MK, Zakaria Z
    J Med Case Rep, 2023 Jun 10;17(1):250.
    PMID: 37296475 DOI: 10.1186/s13256-023-03984-0
    BACKGROUND: The 18q- deletion syndrome is a rare congenital chromosomal disorder caused by a partial deletion of the long arm of chromosome 18. The diagnosis of a patient with this syndrome relies on the family medical history, physical examination, developmental assessment, and cytogenetic findings. However, the phenotype of patients with 18q- deletion syndrome can be highly variable, ranging from almost normal to severe malformations and intellectual disability, and normal cytogenetic findings are common, thus complicating the diagnosis. Interestingly, only few characteristic features of typical 18q- deletion syndrome were found in the patient, despite sharing the same critical region. To our knowledge, this is the first report of a Malaysian individual with 18q- terminal microdeletion diagnosed with microarray-based technology.

    CASE PRESENTATION: Here we report a 16-year-old Malaysian Chinese boy, a product of a non-consanguineous marriage, who presented with intellectual disability, facial dysmorphism, high arched palate, congenital talipes equinovarus (clubfoot), congenital scoliosis, congenital heart defect, and behavioral problems. A routine chromosome analysis on 20 metaphase cells showed a normal 46, XY G-banded karyotype. Array-based comparative genomic hybridization was performed using a commercially available 244 K 60-mer oligonucleotide microarray slide according to the manufacturer's protocol. This platform allows genome-wide survey and molecular profiling of genomic aberrations with an average resolution of about 10 kB. In addition, multiplex ligation-dependent probe amplification analysis was carried out using SALSA MLPA kit P320 Telomere-13 to confirm the array-based comparative genomic hybridization finding. Array-based comparative genomic hybridization analysis revealed a 7.3 MB terminal deletion involving chromosome band 18q22.3-qter. This finding was confirmed by multiplex ligation-dependent probe amplification, where a deletion of ten probes mapping to the 18q22.3-q23 region was detected, and further multiplex ligation-dependent probe amplification analysis on his parents showed the deletion to be de novo.

    CONCLUSION: The findings from this study expand the phenotypic spectrum of the 18q- deletion syndrome by presenting a variation of typical 18q- deletion syndrome features to the literature. In addition, this case report demonstrated the ability of the molecular karyotyping method, such as array-based comparative genomic hybridization, to assist in the diagnosis of cases with a highly variable phenotype and variable aberrations, such as 18q- deletion syndrome.

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