MyMedR

Displaying publications 21 - 32 of 32 in total

Abstract:

Sort:

GRIN2D variants in three cases of developmental and epileptic encephalopathy

Tsuchida N, Hamada K, Shiina M, Kato M, Kobayashi Y, Tohyama J, et al.

Clin Genet, 2018 12;94(6):538-547.
PMID: 30280376 DOI: 10.1111/cge.13454

N-methyl-d-aspartate (NMDA) receptors are glutamate-activated ion channels that are widely distributed in the central nervous system and essential for brain development and function. Dysfunction of NMDA receptors has been associated with various neurodevelopmental disorders. Recently, a de novo recurrent GRIN2D missense variant was found in two unrelated patients with developmental and epileptic encephalopathy. In this study, we identified by whole exome sequencing novel heterozygous GRIN2D missense variants in three unrelated patients with severe developmental delay and intractable epilepsy. All altered residues were highly conserved across vertebrates and among the four GluN2 subunits. Structural consideration indicated that all three variants are probably to impair GluN2D function, either by affecting intersubunit interaction or altering channel gating activity. We assessed the clinical features of our three cases and compared them to those of the two previously reported GRIN2D variant cases, and found that they all show similar clinical features. This study provides further evidence of GRIN2D variants being causal for epilepsy. Genetic diagnosis for GluN2-related disorders may be clinically useful when considering drug therapy targeting NMDA receptors.

Matched MeSH terms: Developmental Disabilities/diagnosis*; Developmental Disabilities/genetics*
Fulltext RAC1 Missense Mutations in Developmental Disorders with Diverse Phenotypes

Reijnders MRF, Ansor NM, Kousi M, Yue WW, Tan PL, Clarkson K, et al.

Am J Hum Genet, 2017 Sep 07;101(3):466-477.
PMID: 28886345 DOI: 10.1016/j.ajhg.2017.08.007

RAC1 is a widely studied Rho GTPase, a class of molecules that modulate numerous cellular functions essential for normal development. RAC1 is highly conserved across species and is under strict mutational constraint. We report seven individuals with distinct de novo missense RAC1 mutations and varying degrees of developmental delay, brain malformations, and additional phenotypes. Four individuals, each harboring one of c.53G>A (p.Cys18Tyr), c.116A>G (p.Asn39Ser), c.218C>T (p.Pro73Leu), and c.470G>A (p.Cys157Tyr) variants, were microcephalic, with head circumferences between -2.5 to -5 SD. In contrast, two individuals with c.151G>A (p.Val51Met) and c.151G>C (p.Val51Leu) alleles were macrocephalic with head circumferences of +4.16 and +4.5 SD. One individual harboring a c.190T>G (p.Tyr64Asp) allele had head circumference in the normal range. Collectively, we observed an extraordinary spread of ∼10 SD of head circumferences orchestrated by distinct mutations in the same gene. In silico modeling, mouse fibroblasts spreading assays, and in vivo overexpression assays using zebrafish as a surrogate model demonstrated that the p.Cys18Tyr and p.Asn39Ser RAC1 variants function as dominant-negative alleles and result in microcephaly, reduced neuronal proliferation, and cerebellar abnormalities in vivo. Conversely, the p.Tyr64Asp substitution is constitutively active. The remaining mutations are probably weakly dominant negative or their effects are context dependent. These findings highlight the importance of RAC1 in neuronal development. Along with TRIO and HACE1, a sub-category of rare developmental disorders is emerging with RAC1 as the central player. We show that ultra-rare disorders caused by private, non-recurrent missense mutations that result in varying phenotypes are challenging to dissect, but can be delineated through focused international collaboration.

Matched MeSH terms: Developmental Disabilities/genetics*; Developmental Disabilities/pathology
Fulltext Familial complex chromosomal rearrangement in a dysmorphic child with global developmental delay

Ngim CF, Keng WT, Ariffin R

Singapore Med J, 2011 Oct;52(10):e206-9.
PMID: 22009409

We report the unusual case of a dysmorphic child with global developmental delay secondary to a familial complex chromosomal rearrangement (CCR). His chromosomal analysis using G-banding and dual colour fluorescence in situ hybridisation with whole chromosome paint revealed a supernumerary marker chromosome as a result of malsegregation of a familial CCR involving chromosomes 7, 12 and 14. The balanced form of this familial CCR was also carried by the patient's mother and maternal grandmother, both of whom had a history of recurrent spontaneous abortions, as well as his maternal uncle, who was infertile. To the best of our knowledge, this is the first reported case of familial CCR involving chromosomes 7, 12 and 14. This case also highlights the importance of chromosomal analysis in children with dysmorphism and developmental delay as well as in adults who suffer from recurrent spontaneous abortions or infertility.

Matched MeSH terms: Developmental Disabilities/genetics*; Developmental Disabilities/physiopathology
Fulltext Cri-du-chat syndrome: application of array cgh in diagnostic evaluation

Juriza, I., Sharifah Azween, S.O., Azli, I., Zarina, A.L., Mohd Fadly, M.A., Zubaidah, Z., et al.

Medicine & Health, 2010;5(2):108-113.
MyJurnal

The human genome contains many submicroscopic copy number variations which includes deletions, duplications and insertions. Although conventional karyotyping remains an important diagnostic tool in evaluating a dysmorphic patient with mental retardation, molecular diagnostic technology such as array comparative genomic hybridization (aCGH) has proven to be sensitive and reliable in detecting these submicroscopic anomalies. A 3 month-old infant with dysmorphic facies, microcephaly and global developmental delay was referred for genetic evaluation. Preliminary karyotyping which was confounded by the quality of metaphase spread was normal; however, aCGH detected a 30.6Mb deletion from 5p15.33-p13.3. This case illustrates the usefulness of aCGH as an adjunctive investigative tool for detecting chromosomal imbalances.

Matched MeSH terms: Developmental Disabilities
Fulltext Neurodevelopmental outcome of newborns with persistent pulmonary hypertension

Rohana J, Boo NY, Chandran V, Sarvananthan R

Malays J Med Sci, 2011 Oct;18(4):58-62.
PMID: 22589673 MyJurnal

Developmental disabilities have been reported in infants with persistent pulmonary hypertension of the newborn (PPHN) treated with inhaled nitric oxide (INO) or intravenous magnesium sulphate (MgSO(4)) and/or extracorporeal membrane oxygenation. This paper reports the rate of developmental disabilities at 2 years of age in a cohort of survivors of PPHN treated with INO, MgSO(4), or both during the neonatal period.

Matched MeSH terms: Developmental Disabilities
Fulltext Clinical features and associated radiological abnormalities in 54 patients with cavum septi pellucidi

Guru Raj AK, Pratap RC, Jayakumar R, Ariffin WA

Med J Malaysia, 1998 Sep;53(3):251-6.
PMID: 10968162

To determine the clinical and radiological features of the patients who were found to have cavum septum pellucidum (CSP) on the cranial computerized tomographic (CT) scans.

Matched MeSH terms: Developmental Disabilities/etiology*
Relationship between head growth and neurodevelopmental outcome of Malaysian very low birthweight infants during the 1st year of life

Ong LC, Boo NY, Chandran V, Zamratol SM, Allison L, Teoh SL, et al.

Ann Trop Paediatr, 1997 Sep;17(3):209-16.
PMID: 9425375

A prospective study was carried out to (i) compare head growth patterns of 103 very low birthweight (VLBW, < 1500 g) Malaysian infants and 98 normal birthweight (NBW, 2500- < 4500 g) controls during the 1st year of life; and (ii) examine the relationship between neurodevelopmental outcome at 1 year of age and occipito-frontal head circumferences (OFC) at birth and at 1 year of age in VLBW babies. When compared with those of NBW infants at birth, mid-infancy and 1 year of age, the mean OFC ratios (observed/expected OFC at 50th percentile) of VLBW infants were significantly lower (p < 0.001). Small-for-gestational-age (SGA) VLBW babies had significantly lower mean OFC ratios than their appropriate-for-gestational-age (AGA) VLBW counterparts at birth (p < 0.001), but this difference was no longer seen at mid-infancy or at 1 year of age. Logistic regression analysis showed that abnormal late neonatal cranial ultrasound findings (odds ratio 8.5, 95% confidence interval 4.12-22.07; p < 0.001) and each additional day of oxygen therapy (odds ratio 1.15, 95% confidence interval 1.00-4.45; p = 0.045) were significant risk factors associated with neurodevelopmental disability at 1 year of age, while mean OFC ratios at birth or at 1 year of age were not. Poor postnatal head growth per se did not predict disability, but probably reflected the consequences of "brain injury" as evidenced by abnormal brain scans.

Matched MeSH terms: Developmental Disabilities/etiology*
Fulltext A case study of distinctive phenotypes arising from emanuel syndrome in two karyotypically identical patients

Mot Yee Yik, Rabiatul Basria S.M.N. Mydin, Emmanuel Jairaj Moses, Shahrul Hafiz Mohd Zaini, Abdul Rahman Azhari, Narazah Mohd Yusoff

Malaysian Journal of Medicine and Health Sciences, 2020;16(102):78-80.
MyJurnal

Emanuel syndrome, also referred to as supernumerary der(22) or t(11;22) syndrome, is a rare genomic syndrome. Patients are normally presented with multiple congenital anomalies and severe developmental disabilities. Affected newborns usually carry a derivative chromosome 22 inherited from either parent, which stems from a balanced translocation between chromosomes 11 and 22. Unfortunately, identification of Emanuel syndrome carriers is diffi- cult as balanced translocations do not typically present symptoms. We identified two patients diagnosed as Emanuel syndrome with identical chromosomal aberration: 47,XX,+der(22)t(11;22)(q24;q12.1)mat karyotype but presenting variable phenotypic features. Emanuel syndrome patients present variable phenotypes and karyotypes have also been inconsistent albeit the existence of a derivative chromosome 22. Our data suggests that there may exist ac- companying genetic aberrations which influence the outcome of Emanuel syndrome phenotypes but it should be cautioned that more patient observations, diagnostic data and research is required before conclusions can be drawn on definitive karyotypic-phenotypic correlations.

Matched MeSH terms: Developmental Disabilities
Fulltext Autism: awareness and perception among Malaysian Nursing Students in Sabah

Deena Clare Thomas, Julie C M, Helda A H, Nurhani Nadiah B, Ranita M

Malaysian Journal of Medicine and Health Sciences, 2020;16(105):71-0.
MyJurnal

Introduction: Autism spectrum disorder (ASD) is a developmental disability that can cause significant social, com- munication and behavioral challenges. According to the 2017 survey by the Ministry of Health Malaysia, children between the ages of 18 to 26 months showed ASD occurs approximately 1.6 in1000 children. In Sabah, 400 autistic children had been registered under Sabah Autism Society (SAS). The increasing prevalence of ASD had become a major concern not only to the parents but to the community. A correct understanding and perception about ASD are crucial especially to the nursing profession as they must be able to educate caregiver on how to manage patients with ASD. Methods: This is a quantitative study using a cross-sectional approach. The respondents are all nursing students in Sabah. The type of sampling is purposive, which is using snowball sampling methods. Research instruments were developed and distributed to all nursing colleges in Sabah. Results: A total of 115 students responded. The majority of age is within range of 18–20 years old and female students. Fifty percents (50%) respondents perceived that of autism is a socio-emotional and neuro-developmental disorder with a non-verbal behaviors’ impairment, curable disorder with proper treatment. More than fifty percent (50%) disagree that autistic child does not want friends and equivalent stand on the statement about autistic child can live independently. Ninety five percent (90%) agree that social media plays an important platform to deliver facts about autism, and health care provider remains as a key role to increase the level of awareness to the community. Conclusion: Results of this study revealed that nursing students in Sabah have a good awareness and perception towards autistic disorder. Nursing students in Sabah agree that social media plays a vital part to increase the level of awareness and perception.

Matched MeSH terms: Developmental Disabilities
Severe mental retardation following asymptomatic hypoglycaemia in an infant with nesidioblastosis

Rahmah, R., Wu, L.L., Roziana, A., Swaminathan, M., Kuhnle, U.

Malaysian Journal of Child Health, 1997;9(1):93-96.
MyJurnal

Nesidioblastosis is a rare metabolic disease characterised by inappropriate insulin secretion often associated with life-threatening hypoglycaemia. While severe cases present in the newborn period, patients have been described later in infancy. Familial cases suggest an autosomal recessive trait, and recently mutations in the sulphonlurea receptor gene, possibly a regulator of insulin secretion, have been identified and associated with disease expression. We report a twin boy who developed normally until the age of six months when he was noted to regress. The boy is the older twin born to non-consanguinous parents. He presented to a hospital first at the age of 13 months with fever and generalised seizures. Low blood glucose was noted, but he recovered easily and was able to maintain euglycaemia during a 48-hour period of observation. Microcephaly and developmental delay were documented and anticonvulsant therapy was started. At 18 months, low blood glucose with high C-peptide was documented during reevaluation. Follow-ing a short trial of subcutaneous long-acting somatostatin analogue, the child was subjected to near-total pancreatectomy. The histology revealed findings consistent with nesidioblastosis. The child's condition improved but he remained significantly delayed This case emphasises the importance of recognising and treating hypoglycaemia early to avoid irreversible brain damage. It is interesting to note that the twin brother has always been well and is developmentally normal. Further studies to identify the inheritance pattern in the family would be of great interest.

Matched MeSH terms: Developmental Disabilities
Fulltext Molecular analysis of fragile X syndrome (FXS) among Malaysian patients with developmental disability

Ali EZ, Yakob Y, Md Desa N, Ishak T, Zakaria Z, Ngu LK, et al.

Malays J Pathol, 2017 08;39(2):99-106.
PMID: 28866690 MyJurnal

Fragile X syndrome (FXS) is a neurodevelopmental disorder commonly found worldwide, caused by the silencing of fragile X mental retardation 1 (FMR1) gene on the X-chromosome. Most of the patients lost FMR1 function due to an expansion of cytosine-guanine-guanine (CGG) repeat at the 5' untranslated region (5'UTR) of the gene. The purpose of this study is to identify the prevalence of FXS and characterize the FMR1 gene CGG repeats distribution among children with developmental disability in Malaysia. Genomic DNA of 2201 samples from different ethnicities (Malays, Chinese, Indian and others) of both genders were PCR-amplified from peripheral blood leukocytes based on specific primers at 5'UTR of FMR1 gene. Full mutations and mosaics were successfully identified by triple methylation specific PCR (ms-PCR) and subsequently verified with FragilEase kit. The findings revealed for the first time the prevalence of FXS full mutation in children with developmental disability in Malaysia was 3.5%, a slightly higher figure as compared to other countries. Molecular investigation also identified 0.2% and 0.4% probands have permutation and intermediate alleles, respectively. The CGG repeats length observation showed 95% of patients had normal alleles within 11 to 44 CGG repeats; with 29 repeats found most common among Malays and Indians while 28 repeats were most common among Chinese. In conclusion, this is the first report of prevalence and characterisation of CGG repeats that reflects genetic variability among Malaysian ethnic grouping.

Matched MeSH terms: Developmental Disabilities
Fulltext Cochlear implantation outcomes in children with multiple disabilities: a topic that's worth revisiting

Bee-See G, Zulkefli NAM, Abdullah A, Umat C, Nor NK, Ismail J, et al.

Braz J Otorhinolaryngol, 2024;90(4):101423.
PMID: 38657449 DOI: 10.1016/j.bjorl.2024.101423

OBJECTIVES: To determine the benefits of cochlear implantation in hearing loss children with multiple disabilities (MD) in terms of auditory outcomes, speech performance, and their quality of life.
METHODS: This was a cross sectional study from January 2019 to December 2020 in which thirty-one children with hearing loss and multiple disabilities were evaluated. Their improvement in auditory and speech performances were assessed using Categories of Auditory Performance version II (CAP-II) and the Speech Intelligibility Rating (SIR) scales. The assessment was done at 6-month intervals, with the baseline evaluation done at least six months after activation of the implant. Parents were asked to fill the Parents Evaluation of Aural/Oral Performance of Children (PEACH) diary and Perceived Benefit Questionnaire (PBQ) to evaluate the child's quality of life.
RESULTS: All 31 children have Global Developmental Delay (GDD), with 11 having an additional disability. Both mean CAP-II and SIR scores showed significant improvement with increased hearing age (p 

Matched MeSH terms: Developmental Disabilities

Filters

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links