KCTD7-related progressive myoclonic epilepsy: Report of 42 cases and review of literature.

OBJECTIVE: KCTD7-related progressive myoclonic epilepsy (PME) is a rare autosomal-recessive disorder. This study aimed to describe the clinical details and genetic variants in a large international cohort. METHODS: Families with molecularly confirmed diagnoses of KCTD7-related PME were identified through international collaboration. Furthermore, a systematic review was done to identify previously reported cases. Salient demographic, epilepsy, treatment, genetic testing, electroencephalographic (EEG), and imaging-related variables were collected and summarized. RESULTS: Forty-two patients (36 families) were included. The median age at first seizure was 14 months (interquartile range = 11.75-22.5). Myoclonic seizures were frequently the first seizure type noted (n = 18, 43.9%). EEG and brain magnetic resonance imaging findings were variable. Many patients exhibited delayed development with subsequent progressive regression (n = 16, 38.1%). Twenty-one cases with genetic testing available (55%) had previously reported variants in KCTD7, and 17 cases (45%) had novel variants in KCTD7 gene. Six patients died in the cohort (age range = 1.5-21 years). The systematic review identified 23 eligible studies and further identified 59 previously reported cases of KCTD7-related disorders from the literature. The phenotype for the majority of the reported cases was consistent with a PME (n = 52, 88%). Other reported phenotypes in the literature included opsoclonus myoclonus ataxia syndrome (n = 2), myoclonus dystonia (n = 2), and neuronal ceroid lipofuscinosis (n = 3). Eight published cases died over time (14%, age range = 3-18 years). SIGNIFICANCE: This study cohort and systematic review consolidated the phenotypic spectrum and natural history of KCTD7-related disorders. Early onset drug-resistant epilepsy, relentless neuroregression, and severe neurological sequalae were common. Better understanding of the natural history may help future clinical trials.

Stillbirth undercount in the sample registration system and national family health survey, India.

Objective: To assess the extent of under-reporting of stillbirths in India by comparing stillbirth and neonatal mortality rates from two national data sources and to review possible reasons for undercounting of stillbirths. Methods: We extracted data on stillbirth and neonatal mortality rates from the annual reports for 2016-2020 of the sample registration system, the Indian government's main source of vital statistics. We compared the data with estimates of stillbirth and neonatal mortality rates from the fifth round of the Indian national family health survey covering events from 2016-2021. We reviewed the questionnaires and manuals from both surveys and compared the sample registration system's verbal autopsy tool with other international tools. Findings: The stillbirth rate for India from the national family health survey (9.7 stillbirths per 1000 births; 95% confidence interval: 9.2-10.1) was 2.6 times higher than the average rate reported in the sample registration system over 2016-2020 (3.8 stillbirths per 1000 births). However, neonatal mortality rates in the two data sources were similar. We identified issues with the definition of stillbirth, documentation of gestation period, and categorization of miscarriages and abortions that could result in undercounting stillbirths in the sample registration system. In the national family health survey only one adverse pregnancy outcome is documented, irrespective of the number of adverse pregnancy outcomes in the given period. Conclusion: For India to attain its 2030 target of single-digit stillbirth rate and to monitor actions to end preventable stillbirths, efforts are needed to improve the documentation of stillbirths in its data collection systems.

Primary amoebic meningoencephalitis in children- report of two cases from South India.

Primary Amoebic meningoencephalitis is a rare and fatal neuro-infection caused by free-living fresh-water amoeba Naegleria fowleri. It is a ubiquitous organism and the infection occurs usually via contact with warm water-bodies. The clinical presentation is often indistinguishable from acute bacterial meningitis and the diagnosis can be made by CSF wet smear examination if there is a high index of suspicion. The disease progresses rapidly compared to pyogenic meningitis and usually has a fatal outcome. Reports of two confirmed cases of primary amoebic meningoencephalitis in children from different centres in Kerala state of India are presented here. In spite of early diagnosis and treatment, both these patients demised. Primary amoebic meningoencephalitis should be considered in the differential diagnosis of acute meningitis, especially in patients with recent freshwater exposure. Implementation of chlorination of pools of water bodies, especially if re-opened for recreational purpose after prolonged periods of non-use, needs vigorous implementation.