Association of Child Neurology-Indian Epilepsy Society Consensus Document on Parental Counseling of Children with Epilepsy.

When a child is diagnosed with epilepsy, counseling regarding the same is done by the treating doctor. Most parents are frightened and have poor knowledge about epilepsy. Therapeutic advice including drug dosage, administration and side effects takes up the major part of physician's time, thereby neglecting important issues like home seizure management, follow up and others. These lacunae in knowledge require systematic patient and family education. To address these issues, an expert group meeting of pediatric neurologists and epileptologists in India along with social workers/epilepsy educators, legal experts, parents, and teachers was held. The various aspects regarding parental counseling in children with epilepsy were discussed and a consensus document was formulated. Here authors present the group consensus statement on counseling parents and caregivers of children with epilepsy. This document is intended to help physicians and pediatricians counsel the families when a child is diagnosed with epilepsy.

Neurodevelopmental disorders in children aged 2-9 years: Population-based burden estimates across five regions in India.

BACKGROUND: Neurodevelopmental disorders (NDDs) compromise the development and attainment of full social and economic potential at individual, family, community, and country levels. Paucity of data on NDDs slows down policy and programmatic action in most developing countries despite perceived high burden. METHODS AND FINDINGS: We assessed 3,964 children (with almost equal number of boys and girls distributed in 2-<6 and 6-9 year age categories) identified from five geographically diverse populations in India using cluster sampling technique (probability proportionate to population size). These were from the North-Central, i.e., Palwal (N = 998; all rural, 16.4% non-Hindu, 25.3% from scheduled caste/tribe [SC-ST] [these are considered underserved communities who are eligible for affirmative action]); North, i.e., Kangra (N = 997; 91.6% rural, 3.7% non-Hindu, 25.3% SC-ST); East, i.e., Dhenkanal (N = 981; 89.8% rural, 1.2% non-Hindu, 38.0% SC-ST); South, i.e., Hyderabad (N = 495; all urban, 25.7% non-Hindu, 27.3% SC-ST) and West, i.e., North Goa (N = 493; 68.0% rural, 11.4% non-Hindu, 18.5% SC-ST). All children were assessed for vision impairment (VI), epilepsy (Epi), neuromotor impairments including cerebral palsy (NMI-CP), hearing impairment (HI), speech and language disorders, autism spectrum disorders (ASDs), and intellectual disability (ID). Furthermore, 6-9-year-old children were also assessed for attention deficit hyperactivity disorder (ADHD) and learning disorders (LDs). We standardized sample characteristics as per Census of India 2011 to arrive at district level and all-sites-pooled estimates. Site-specific prevalence of any of seven NDDs in 2-<6 year olds ranged from 2.9% (95% CI 1.6-5.5) to 18.7% (95% CI 14.7-23.6), and for any of nine NDDs in the 6-9-year-old children, from 6.5% (95% CI 4.6-9.1) to 18.5% (95% CI 15.3-22.3). Two or more NDDs were present in 0.4% (95% CI 0.1-1.7) to 4.3% (95% CI 2.2-8.2) in the younger age category and 0.7% (95% CI 0.2-2.0) to 5.3% (95% CI 3.3-8.2) in the older age category. All-site-pooled estimates for NDDs were 9.2% (95% CI 7.5-11.2) and 13.6% (95% CI 11.3-16.2) in children of 2-<6 and 6-9 year age categories, respectively, without significant difference according to gender, rural/urban residence, or religion; almost one-fifth of these children had more than one NDD. The pooled estimates for prevalence increased by up to three percentage points when these were adjusted for national rates of stunting or low birth weight (LBW). HI, ID, speech and language disorders, Epi, and LDs were the common NDDs across sites. Upon risk modelling, noninstitutional delivery, history of perinatal asphyxia, neonatal illness, postnatal neurological/brain infections, stunting, LBW/prematurity, and older age category (6-9 year) were significantly associated with NDDs. The study sample was underrepresentative of stunting and LBW and had a 15.6% refusal. These factors could be contributing to underestimation of the true NDD burden in our population. CONCLUSIONS: The study identifies NDDs in children aged 2-9 years as a significant public health burden for India. HI was higher than and ASD prevalence comparable to the published global literature. Most risk factors of NDDs were modifiable and amenable to public health interventions.

Consensus Statement of the Indian Academy of Pediatrics on Evaluation and Management of Attention Deficit Hyperactivity Disorder.

JUSTIFICATION: Attention-Deficit/Hyperactivity Disorder (ADHD) is highly prevalent in children worldwide. Management of ADHD requires a systematic, multidisciplinary approach and therefore evidence-based, standardized national guidelines are essential. PROCESS: A meeting for formulation of national consensus guidelines on neurodevelopmental disorders was organized by Indian Academy of Pediatrics in Mumbai, on 18th and 19th December, 2015. The invited experts included Pediatricians, Developmental Pediatricians, Pediatric Neurologists, Psychiatrists, Remedial Educators and Clinical Psychologists. The participants framed guidelines after extensive discussions. OBJECTIVE: To provide consensus guidelines on evaluation and management of ADHD in children in India. RECOMMENDATIONS: ADHD is a chronic condition and thus education of patients, families, and teachers regarding the diagnosis is an integral part of management. Involvement of patient the and the family in the management program is extremely vital. Management of ADHD centers on the achievement of target outcomes, which are chosen in collaboration with the child, parents, and school personnel. Coexisting conditions must be treated concurrently with ADHD. Modalities of management of ADHD include behavioral interventions, medications, and educational interventions. These modalities can be implemented individually or in combination.

Profile of prothrombotic factors in Indian children with ischemic stroke.

This study was undertaken in view of paucity of data regarding the profile of prothrombotic factors in children with ischemic stroke. Sixty-four children with ischemic stroke were prospectively evaluated for prothrombotic factors over a 2 year period. The blood samples were analyzed for protein C (PC), protein S (PS), activated protein C resistance (APCR), factor V Leiden (FVL), anti-thrombin-III (AT-III), lipoprotein (a) [Lp(a)], lupus anticoagulant (LA), anti-cardiolipin antibodies (aCL) immunoglobulin (Ig) M and IgG, homocysteine, and methylenetetrahydrofolate reductase (MTHFR) at least 3 months after the onset of stroke. At least one prothrombotic factor was identified in 45.3% children (29/64). These included hyperhomocysteinemia (11/64), PC deficiency (9/64), aCL (8/64), PS deficiency (5/64), APCR (3/64), AT-III deficiency (2/64) and LA (1/64). Multiple factors were coexistent in 17.2% (11/64). The prevalence of PC deficiency, PS deficiency and co-existence of multiple abnormalities observed were similar to the published literature. Elevated Lp(a) and APCR were less prevalent. FVL and MTHFR were not seen in any of the study children. Forty-five percent of children had at least one prothrombotic abnormality. Hyperhomocysteinemia, PC deficiency, aCL and PS deficiency were the most frequent prothrombotic abnormalities.

Noninvasive screening for preclinical atherosclerosis in children on phenytoin or carbamazepine monotherapy: a cross sectional study.

PURPOSE: This study was carried out to compare the carotid Intimal Media Thickness (IMT), and endothelial function using brachial flow mediated dilatation (FMD), in Epileptic children (6-12 years) on phenytoin (PHT) or carbamazepine (CBZ) monotherapy for ≥18 months with a control group of children. METHODS: In this cross-sectional study 30 children (aged 6-12 years) on PHT monotherapy and 28 children on CBZ monotherapy were compared with an equal number of apparently healthy age and sex matched children unexposed to antiepileptics. Fasting lipids, sugar, Hs-CRP levels and ultrasonographic assessment of carotid IMT and endothelial function using brachial FMD were conducted. RESULTS: The age (years) of the children in the CBZ group (9.1±2), PHT group (9.4±2) and the controls (9.3±2) was comparable. The duration of CBZ therapy was 30.8±13.2 months and that of PHT therapy was 29.5±13.6 months. The mean dose of CBZ was 18.18±8.5mg/kg and that of PHT was 5.5±2.3mg/kg body weight. The time since last seizure was 15.6±8.4 months in the CBZ group and 17.3±10.4 months in the PHT group. The fasting blood sugar was below 110mg/dl in all children. The height, weight, waist and hip measurements, waist hip ratio and blood pressures were similar in the groups. The total cholesterol levels (161.7±24.8 vs 140.2±20.8mg/dl, p=0.001), HDL (53.8±10.5 vs 47.1±8.8mg/dl, p=0.017) and LDL (85±21.1 vs 70.9±19.4mg/dl, p=0.01) were significantly higher in the CBZ group compared to the control group. The HDL levels (54.6±9.4 vs 45.8±7.7mg/dl, p<0.0001) were significantly higher in the PHT group compared to the control group. The right carotid (0.374±0.04 vs 0.339±0.05mm, p=0.012), left carotid (0.382±0.05 vs 0.351±0.05mm, p=0.044) and the overall average carotid intima media thickness (0.378±.048 vs 0.345±.052mm, p=0.018) of the children on CBZ was significantly higher than the carotid IMT in control group children. The right carotid (0.370±0.04 vs 0.342±0.05mm, p=0.032) and the overall average carotid IMT (0.374±0.04 vs 0.348±0.05mm, p=0.035) of the children on PHT was significantly higher than the carotid IMT in controls. The FMD were comparable in the children on CBZ or PHT and the control group. CONCLUSIONS: The results are preliminary but could signal the increased vulnerability of epileptic children on long term antiepileptics to have subclinical atherosclerosis.

Blood lead levels among school children after phasing-out of leaded petrol in Delhi, India.

OBJECTIVES: The use of leaded petrol was prohibited in the Delhi city by the end of 1998. To determine the impact of use of unleaded petrol, this cross-sectional study was conducted to determine blood lead levels in primary school children. METHODS: Blood lead levels were estimated in 300 school children aged 6 to 10 y. The data regarding clinical features and putative risk factors for high blood lead levels was also collected. RESULTS: Of the 300 children, 36 (12 %) had high blood lead levels. Of the 36 children, 32 had blood lead levels between 10 and 19 µg/dl, 4 had 20-44 µg/dl and none had levels >45 µg/dl. Factors such as exposure to peeling paint, recent renovation of housing and near-distance of house to main road were significantly associated with high blood lead levels. CONCLUSIONS: There is significant prevalence of high blood lead levels in school children in Delhi, even after with prohibition of use of leaded petrol.

Effectiveness and safety of donepezil in boys with fragile x syndrome: a double-blind, randomized, controlled pilot study.

The present study was designed as a 12-week, randomized, double-blind, placebo-controlled pilot study to evaluate the effectiveness and safety of donepezil in boys with fragile X syndrome. Twenty boys with fragile X syndrome were randomized to receive 12 weeks of treatment with either placebo or donepezil (2.5 mg daily for initial 4 weeks followed by 5 mg daily for next 8 weeks). The outcome measures included change in intelligence quotient scores on Stanford-Binet Intelligence Scale (Hindi adaptation by Kulshrestha), change in behavioral scores by Conners 3 Parent Rating Scale (Short) and Childhood Autism Rating Scale, safety, and tolerability of donepezil. The study failed to show significant difference in intelligence quotient and behavioral scales with donepezil therapy over 12 weeks. However, donepezil appeared to be safe and well tolerated.

Efficacy of modified constraint induced movement therapy in improving upper limb function in children with hemiplegic cerebral palsy: a randomized controlled trial.

PURPOSE: The objective of this randomized single blind (outcome assessor) controlled trial was to evaluate the efficacy of 4 weeks of modified constraint induced movement therapy (mCIMT) in improving upper limb function in 3-8 years old children with hemiplegic cerebral palsy. METHODS: Thirty-one children were randomly assigned to receive the mCIMT (N=16) with conventional therapy or conventional therapy alone (N=15). Children were evaluated three times (at enrollment, follow up at 4 weeks and 12 weeks). The primary outcome measure was difference in "change in mean total QUEST scores" at 4 weeks of intervention between the intervention and the control arm. RESULTS: After 4 weeks of intervention, mCIMT group showed significant change in the affected upper limb in QUEST scores (10.7 ± 5.2 vs 1.4 ± 1.7, p<0.001) and time (s) to complete nine-hole-pegboard test compared with control group [60(0-130) vs 5(-12 to 30), p<0.001]. The improvement observed in upper limb function after 4 weeks of intervention persisted 8 weeks after discontinuation of intervention in mCIMT group. CONCLUSION: The modified constraint induced movement therapy appears to be effective in improving upper limb function in 3-8 years old hemiplegic cerebral palsy children.

Detection of Mycobacterium tuberculosis GlcB or HspX Antigens or devR DNA impacts the rapid diagnosis of tuberculous meningitis in children.

BACKGROUND: Tuberculous meningitis (TBM) is the most common form of neurotuberculosis and the fifth most common form of extrapulmonary TB. Early diagnosis and prompt treatment are the cornerstones of effective disease management. The accurate diagnosis of TBM poses a challenge due to an extensive differential diagnosis, low bacterial load and paucity of cerebrospinal fluid (CSF) especially in children. METHODOLOGY/PRINCIPAL FINDINGS: We describe the utility of ELISA and qPCR for the detection of Mycobacterium tuberculosis (M. tb) proteins (GlcB, HspX, MPT51, Ag85B and PstS1) and DNA for the rapid diagnosis of TBM. CSF filtrates (n = 532) derived from children were classified as 'Definite' TBM (M. tb culture positive, n = 29), 'Probable and Possible' TBM (n = 165) and 'Not-TBM' including other cases of meningitis or neurological disorders (n = 338). ROC curves were generated from ELISA and qPCR data of 'Definite' TBM and Non-Tuberculous infectious meningitis (NTIM) samples and cut-off values were derived to provide ≥ 95% specificity. devR qPCR, GlcB, HspX and PstS1 ELISAs showed 100% (88;100) sensitivity and 96-97% specificity in 'Definite' TBM samples. The application of these cut-offs to 'Probable and Possible' TBM groups yielded excellent sensitivity (98%, 94;99) and specificity (98%, 96;99) for qPCR and for GlcB, HspX and MPT51 antigen ELISAs (sensitivity 92-95% and specificity 93-96%). A test combination of qPCR with GlcB and HspX ELISAs accurately detected all TBM samples at a specificity of ~90%. Logistic regression analysis indicated that these tests significantly added value to the currently used algorithms for TBM diagnosis. CONCLUSIONS: The detection of M. tb GlcB/HspX antigens/devR DNA in CSF is likely to improve the utility of existing algorithms for TBM diagnosis and also hasten the speed of diagnosis.

Novel non-identical MECP2 mutations in Rett syndrome family: a rare presentation.

INTRODUCTION: Rett syndrome (RS), an X-linked neurodevelopmental disorder and the common cause of mental retardation in females, is caused by methyl CpG binding protein 2 (MECP2) gene mutations with a frequency of more than 95% in classical Rett patients. Majority of RS cases are sporadic but few familial cases caused by either skewed X-chromosome inactivation in healthy female carriers or mosaicism in male carriers are also reported. Most of the times, the mutation carried in a family is the same as found in affected child. METHODS AND RESULTS: Here we report a unique family carrying non-identical MECP2 mutations in exon 2 wherein the proband with classical RS was carrying a de-novo early truncating frameshift mutation while her asymptomatic mother was carrying a missense mutation, both predicted as pathogenic mutations. CONCLUSIONS: These findings further validate the importance of MECP2 mutation screening in parents of all mutation positive patients and careful evaluation of the pathogenicity of the mutation found in asymptomatic carriers before providing genetic counseling to the family. The results also propose the role of other factors including other gene mutations, environmental and epigenetics factors in modifying the expression of MECP2 mutations.

Fourth ventricular hamartoma presenting with status epilepticus treated with emergency surgery in an infant.

A 4-week-old infant presented with hemifacial spasms noticed from the 4th day after delivery. These progressed in severity, with generalization every 3-4 h. On admission, the infant went into refractory status epilepticus and had to be electively ventilated and taken for surgery on a semi-emergency basis. MRI showed a fourth ventricular hamartoma and video EEG showed spikes that were synchronous with the facial 'twitches' with generalization. Following the first surgery, the infant had an initial complete recovery, but developed recurrence of facial twitches after 2 weeks. Repeat MRI showed a small residual tumor which was re-operated and completely excised (at 8 weeks). Following this, the patient had complete recovery from seizures (5-year follow-up). This is the youngest patient reported presenting with status epilepticus with a fourth ventricular hamartoma operated successfully.

Genomic profiling identifies novel mutations and SNPs in ABCD1 gene: a molecular, biochemical and clinical analysis of X-ALD cases in India.

X-linked adrenoleukodystrophy (X-ALD) affects the nervous system white matter and adrenal cortex secondary to mutations in the ABCD1 gene that encode the peroxisomal membrane protein. We conducted a genomic and protein expression study of susceptibility gene with its clinical and biochemical analysis. To the best of our knowledge this is the first preliminary comprehensive study in Indian population that identified novel mutations and SNPs in a relatively large group. We screened 17 Indian indigenous X-linked adrenoleukodystrophy cases and 70 controls for mutations and SNPs in the exonic regions (including flanking regions) of ABCD1 gene by direct sequencing with ABI automated sequencer along with Western blot analysis of its endogenous protein, ALDP, levels in peripheral blood mononuclear cells. Single germ line mutation was identified in each index case in ABCD1 gene. We detected 4 novel mutations (2 missense and 2 deletion/insertion) and 3 novel single nucleotide polymorphisms. We observed a variable protein expression in different patients. These findings were further extended to biochemical and clinical observations as it occurs with great clinical expression variability. This is the first major study in this population that presents a different molecular genetic spectrum as compared to Caucasian population due to geographical distributions of ethnicity of patients. It enhances our knowledge of the causative mutations of X-ALD that grants holistic base to develop effective medicine against X-ALD.

Molecular analysis of ABCD1 gene in Indian patients with X-linked adrenoleukodystrophy.

BACKGROUND: X-linked Adrenoleukodystrophy (X-ALD), with an incidence of 1:14,000 is the most frequent monogenic demyelinating disorder worldwide. The principal biochemical abnormality in X-ALD is the increased levels of saturated, unbranched very long chain fatty acids (VLCFA). It is caused by mutations in ABCD1 gene. No molecular data on X-ALD is available in India and mutational spectrum in Indian patients is not known. METHODS: We standardized conformation sensitive gel electrophoresis (CSGE) method to detect mutations in ABCD1 gene in twenty Indian patients with X-ALD. The results were confirmed by sequencing. Genotype-phenotype correlation was also attempted. Prenatal diagnosis (PND) in one family was done using chorionic villi (CV) sample at 12 weeks of gestation. RESULTS: Out of twenty, causative mutations could be identified in twelve patients (60%). Six reported and four novel mutations were identified. Three polymorphisms were also observed. No hot spot was found. No significant genotype-phenotype correlation could be established. CONCLUSIONS: The study identified the mutation spectrum of Indian X-ALD patients, which enabled us to offer accurate genetic counseling, carrier detection and prenatal diagnosis where needed.

The presence of Mycoplasma pneumoniae infection and GM1 ganglioside antibodies in Guillain-Barré syndrome.

INTRODUCTION: Guillain-Barré syndrome (GBS) is an autoimmune disorder affecting the peripheral nervous system, usually triggered by an acute infection. GBS patients are known to have antecedent bacterial infections associated with auto-antibodies to various gangliosides. This investigation aimed to evaluate GBS patients for serological evidence of Mycoplasma pneumoniae infection and anti GM1 ganglioside antibodies. METHODOLOGY: This cross-sectional study included 57 pediatric GBS patients, 42 neurological controls (i.e., non-GBS Acute Flaccid Paralysis cases) and 35 non-neurological controls. Enzyme linked immune sorbent assay (ELISA) was performed on the sera of the subjects to detect IgM and IgG antibodies against Mycoplasma (M.) pneumoniae and GM1 gangliosides. RESULTS: The results showed that 15.79% and 21.05% GBS patients were positive for IgG and IgM antibodies against M. pneumoniae as compared to 2.38% (P < 0.05) and 14.2% in non-GBS-AFP and 5.7% and 14.2% in non-neurological controls respectively. Additionally, 43.85% and 38.54% GBS patients were positive for IgG and IgM antibodies against GM1 gangliosides as compared to 38.09% and 28.57% in non-GBS-AFP and 14.2% and 2.84% in non-neurological controls respectively (P < 0.05). CONCLUSIONS: Significant difference in levels of IgG antibodies against M. pneumoniae was observed between GBS patients and neurological controls, suggesting M. pneumoniae to be an important antecedent to GBS. Significant difference in levels of anti GM1 ganglioside antibodies (IgG & IgM) was seen between GBS patients and non-neurological controls, highlighting its possible role in the pathogenesis of GBS.

Efficacy of 4:1 (classic) versus 2.5:1 ketogenic ratio diets in refractory epilepsy in young children: a randomized open labeled study.

PURPOSE: The ketogenic (lipid to non-lipid) ratio may play an important role in the efficacy and tolerability of ketogenic diets (KD). This study was planned to compare the efficacy and tolerability of 2.5:1 versus 4:1 lipid:non-lipid ratio KD in young children with refractory epilepsy. METHODS: Children aged 6 months to 5 years with refractory epilepsy were enrolled. They were randomized to receive either a 4:1 or 2.5:1 ketogenic ratio diet, which was introduced using a non-fasting protocol. Seizure frequency, biochemical profile (liver and kidney function tests, fasting lipid profile, and spot urinary calcium-creatinine ratio), and adverse effects were recorded at three months in both groups. RESULTS: Thirty eight children were enrolled, 19 in each group. At three months, 11 children (58%) in the 4:1 group and 12 (63%) in the 2.5:1 group had more than 50% reduction in seizures (p=0.78). Five children (26%) in the 4:1 group and four (21%) in 2.5:1 group became seizure free. There was no significant difference in the biochemical parameters between the two groups. CONCLUSION: 2.5:1 ratio KD is possibly as effective as 4:1 KD in controlling seizures and has fewer adverse effects.

Molecular genetic studies in Indian patients with megalencephalic leukoencephalopathy.

Mutations in the MLC1 gene cause megalencephalic leukoencephalopathy with subcortical cysts. We sought to identify mutations in the MLC1 gene, to evaluate the genotype-phenotype correlation, and to develop a strategy for diagnosing Indian patients with megalencephalic leukoencephalopathy. Forty patients were enrolled. We developed a rapid restriction fragment length polymorphism method to screen a common mutation, c.135_136insC. Rare and novel mutations were screened by conformation-sensitive gel electrophoresis, followed by sequencing. Three previously reported and two novel mutations were identified in 37 patients. The presence of the c.135_136insC mutation in 29 patients of the Agarwal community suggests a founder effect. The mutation c.959C>A was evident in four patients, and appears to be the second commonest mutation. Genotype could not predict phenotype. We recommend screening for the commonest mutation (c.135_136insC), followed by the next commonest mutation (c.959C>A), and then other rare mutations, using conformation-sensitive gel electrophoresis analysis or direct sequencing.

Fundal changes in children receiving Vigabatrin.

Visual field defects and other abnormalities are reported in patients receiving the newer antiepileptic Vigabatrin (VGB). Field testing in children younger than 6 years and those with mental retardation is difficult. The authors, therefore, studied ophthalmoscopic abnormalities in seven pediatric patients receiving VGB for median duration of 9 month (range, 3-32 months). Abnormal findings were seen in two (33.3%) in the form of surface wrinkling retinopathy and abnormal macular reflexes. The proportion of abnormal findings was in agreement with previous reports. Thus it is concluded that simple ophthalmoscopy by an ophthalmologist picks up the abnormalities due to ocular toxicity of VGB, and helps in rationalizing further AED therapy in the clinic.

Intranasal versus intravenous lorazepam for control of acute seizures in children: a randomized open-label study.

PURPOSE: Intravenous lorazepam is considered the drug of first choice for control of acute convulsive seizures. However, resource or personnel constraints necessitate the study of alternative routes and medications. This study compared the efficacy and adverse effects of intranasal versus intravenous lorazepam in children aged 6-14 years who presented with acute seizures. METHODS: This was a randomized open-label study conducted at an Indian hospital from August 2008 to April 2009. One hundred forty-one consecutive children aged 6-14 years who presented convulsing to the emergency room were included. After stabilization, the children were randomized to receive either intravenous or intranasal lorazepam (0.1 mg/kg, maximum 4 mg). The primary outcome measure was clinical seizure remission within 10 min of drug administration. The study was registered with clinicaltrials.gov (NCT00735527). KEY FINDINGS: Seventy patients were randomized to receive intravenous and 71 to receive intranasal lorazepam. The patients in the two groups were comparable at baseline. Clinical seizure remission within 10 min of drug administration was found in 80% of the intravenous group as compared to 83.1% of intranasal group. The lower limit of 95% confidence interval for effect size was approximately -9.7%, with an a priori cutoff for noninferiority of -10%. SIGNIFICANCE: Intranasal administration of lorazepam is not found to be inferior to intravenous administration for termination of acute convulsive seizures in children.

A novel MECP2 change in an indian boy with variant rett phenotype and congenital blindness: implications for genetic counseling and prenatal diagnosis.

Mutations in MECP2 gene are the primary cause of Rett syndrome, a neurodevelopmental disorder that primarily affects girls, and affect 90% to 95% patients with classical Rett syndrome. MECP2 mutations, once thought to be lethal in males, now present a broad spectrum of clinical manifestations in males. This article reports a family with a 9-year-old boy with Rett-like phenotype and congenital blindness, who inherited a novel MECP2 variant (p.P430S) from his asymptomatic mother. The variant was also identified in the asymptomatic maternal grandfather and maternal aunts of the proband, ruling out the possibility that the p.P430S was involved in the phenotype. Findings of the study suggest that a careful evaluation of the pathogenic nature of MECP2 variants identified in males be conducted before proposing genetic counseling or prenatal diagnosis to the family and that the interference of other factors like modifier genes, environment, epigenetics, and mosaicism be taken into account.