Elisabeth Siti Herini

Effects of RET and NRG1 polymorphisms in Indonesian patients with Hirschsprung disease

BACKGROUND Hirschsprung disease (HSCR) is a neurocristopathy characterized by absence of intramural ganglion cells along variable lengths of the gastrointestinal tract in neonates. Three polymorphisms, rs2435357, within a conserved transcriptional enhancer of RET, and, rs7835688 and rs16879552, within intron 1 of NRG1, have been shown to be associated with isolated forms of HSCR. We wished to replicate these findings, and study the interactions between these variants, in Indonesian HSCR patients. METHODS Sixty isolated HSCR patients and 124 controls were ascertained for this study. The three genetic markers were examined using TaqMan Genotyping Assays in genomic DNA for association studies. RESULTS RET rs2435357 showed the strongest association with HSCR both by case-control analysis (p=2.5 × 10(-8)) and transmission disequilibrium test (p=4.2 × 10(-6)). NRG1 rs7835688 was modestly associated with HSCR only by case-control analysis (p=4.3 × 10(-3)), whereas rs16879552 demonstrated no association (p>0.097). Two locus analyses of variants showed significant interactions with increased and decreased disease risks of HSCR at NRG1 but conditional on rs2435357 genotype. CONCLUSIONS RET and NRG1 variants are common susceptibility factors for HSCR in Indonesia. These common variants demonstrate that development of HSCR requires joint effects of RET and NRG1 early in gut development.

Clinical features of infants with subependymal germinolysis and choroid plexus cysts.

Abstract Background : Periventricular cysts arenot rare findings in neonates. However, they are sometimes associated withserious clinical complications, such as congenital viral infectionsand anomalies.

Generalized epilepsy with febrile seizures plus (GEFS+) spectrum: Clinical manifestations and SCN1A mutations in Indonesian patients

Generalized epilepsy with febrile seizures plus (GEFS+) is a childhood genetic epilepsy syndrome. GEFS+ includes a wide spectrum of clinical manifestations, and SCN1A mutations have frequently been reported among the GEFS+-related gene abnormalities. In this study, to clarify the distributions of the clinical subtypes, we analyzed 34 families with GEFS+ in Indonesia using the hospital records of the patients and questionnaires for the family members. The number of patients with febrile seizures plus (FS+), FS+ and afebrile generalized/partial seizures, borderline severe myoclonic epilepsy in infancy (SMEB) and severe myoclonic epilepsy in infancy (SMEI) were 9, 11, 7, and 7, respectively. Most patients had a family history of febrile seizures. Next, we performed molecular analyses to clarify the contributions of SCN1A mutations to the development of the GEFS+ subtypes. Only 3 of 34 probands showed SCN1A mutations. These mutations were two missense mutations, p.V1612I and p.C1756G, in two patients with SMEI and SMEB, and one silent mutation, p.G1762G, in a patient with FS+ and afebrile partial seizures. In conclusion, the majority of GEFS+ patients in Indonesia were not associated with SCN1A mutations. To detect the GEFS+-causing mutations, we must search and analyze other genes in these patients.

Novel SCN1A mutations in Indonesian patients with severe myoclonic epilepsy in infancy

Background:  Severe myoclonic epilepsy in infancy (SMEI) and borderline SMEI (SMEB) are caused by a mutation in SCN1A, which encodes a voltage‐gated sodium channel α1‐subunit protein. Although many mutations in SCN1A have been associated with clinical features of SMEI or SMEB from different ethnic groups, there have been no such reports from the South‐East Asian populations so far.

Usefulness of CBCL/6-18 to evaluate emotional and behavioral problems in Indonesian autism spectrum disorder children

The Child Behavior Checklist (CBCL) has been widely utilized to estimate emotional and behavioral problems in children in the USA and Europe. Although the Indonesian version of the CBCL/6‐18 was proven to have good validity and internal consistency in children with typical development (TD) in Indonesia, it has not been utilized for children with autism spectrum disorder (ASD). The purpose of this study was therefore to investigate the usefulness of CBCL/6‐18 for detecting emotional and behavioral problems in Indonesian ASD children.

Clinical profile of congenital rubella syndrome in Yogyakarta, Indonesia

Congenital rubella syndrome (CRS) has many severe neurological manifestations and other systemic consequences. Although various studies have been done in Indonesia, there are no conclusive results on CRS incidence. The aim of this study was therefore to investigate the incidence, clinical manifestations and outcomes of CRS in Yogyakarta, Indonesia.

Faktor Risiko Sekuele Meningitis Bakterial pada Anak

Latar belakang. Mortalitas akibat meningitis bakterial menurun dengan ditemukan antibotik yang poten dan penanganan yang baik pada saat pasien kritis. Walaupun demikian, sekuele akibat meningitis bakterial masih tinggi, sekitar 50%-65% di negara berkembang. Tujuan. Mengetahui faktor risiko yang terkait dengan sekuele pada pasien meningitis bakterial yang bertahan hidup. Metode. Penelitian kasus kontrol dilakukan di RSUP Dr. Sardjito, RSUD Banyumas dan RSU Suradji Tirtonegoro Klaten. Kasus adalah pasien yang terdiagnosis meningitis bakterial pada tahun 2003 – 2006 yang hidup dengan sekuele. Kontrol adalah pasien meningitis bakterial yang hidup tanpa sekuele. Data diambil dari catatan medis, luaran ditetapkan setelah 6 bulan. Hasil. Terdapat 78 pasien yang memenuhi kriteria inklusi. Hasil analisis multivariat menunjukkan bahwa faktor risiko yang terkait dengan meningitis bakterial adalah kejang >30 menit saat masuk rumah sakit (OR 4,29; IK 95% 1,38–12,99), PCS (Pediatrics Coma Scale) 72 jam (OR 5,24 ; IK 95% 1,49–18,43). Onset - gejala >48 jam mempunyai OR 2,43 (IK 95% 0,73 – 8,13). Kesimpulan. Kejang >30 menit saat masuk rumah sakit, PCS 72 jam merupakan faktor risiko yang indipenden untuk menimbulkan sekuele.

Intracranial hemorrhage in infants after massaged by a traditional birth attendant

Background The overall incidence of birth related injuries declines with the improvement in obstetrics. However, the incidence of head trauma in infants after massaged by a traditional birth attendant (TBA) is still unknown. Objective To study the characteristics of intracranial hemorrhage in infants after massaged by a TBA. Methods A retrospective study was conducted in Sardjito Hospital, Yogyakarta, Indonesia between October 2001 and May 2005. Infants with intracranial hemorrhage after massaged by a TBA were included. Data on patients’ demography, history of massaging by TBA, clinical presentation, and injury characteristics such as anemia, clotting time (CT), bleeding time (BT), prothrombin time (PT) and activated partial thromboplastin time (APTT) were noted. Computed cranial tomography (CT) scans were performed. Results A total of seven infants were diagnosed with intracranial hemorrhage after massaged by a TBA. There were four males and three females (mean age 46 days; range 27-60 days). All infants were referred to Sardjito Hospital, Yogyakarta, Indonesia with bad condition and anemia; mean hemoglobin level was 5.5 g/dl (range 3.7-8.3 g/dl). All infants presented with seizures. Coagulation screening showed normal results in five patients. The remaining patients had a prolonged CT and PT. CT scan showed subdural hemorrhage in four patients, intracerebral hemorrhage in four, epidural hemorrhage in two, and subarachnoid hemorrhage in one. Two patients had chronic hemorrhage, while the rest had acute hemorrhage. Four of them underwent craniotomy, two patients were under an observation only, and one patient was not treated due to parental refusal. Six patients survived and the one who refused to be treated died. Conclusions The parents, midwives, and doctors have to be aware of head massaging since it may harm infants.