A 10-YEAR STUDY OF CHILDREN WITH GONADAL TUMORS AND DISORDERS OF SEX DIFFERENTIATION, IN ROMANIA.

Context: Children having gonadal tumors and disorder of sex differentiation (DSD) are rare. Objective: To investigate the presentation of DSD children with malignant gonadal tumors. Methods: A retrospective study from 2010-2020, that evaluated 17 children with DSD, including 13 females, eight months to 16 years, with congenital adrenal hyperplasia, 5-alpha reductase deficiency, androgen insensitivity syndrome, Turner, Sywer, and Klinefelter syndromes. Results: Ten children had malignant gonadal tumor; nine had germ cell tumors and one person granulosa cell tumors, while seven children with non-malignant tumor had gonadoblastoma, cystadenoma (five children), and cysts. Systemic malformations, obesity, elevated tumor markers, and psychosocial issues were observed in 90%, 90%, 70%, and 50% of children with malignancy unlike 28.6%, 42.9%, 14.35%, and 57.1% children without malignancy respectively. Most (9/10) children >12 years, had psychosocial issues, unlike 0/7 children ≤12 years. From 8/17 children presenting with symptoms suggestive of tumor, 75% had malignancy, while from 9/17 children with DSD presentation, 44% had malignant tumors. Malignancy was observed in 3/10 children between eight months to age six, while 7/10 children had stage 1-2 tumors. We reported a child, identified as female, aged 13 years, with partial androgen insensivity syndrome (PAIS) 46,XY, and testicular papillary serous cystadenoma with genomic variant AR NM_000044.4:c.2750del. p.(F917Sfs*27) chromosome Xq12, never published in people with PAIS nor population databases (GnomAD). Conclusion: DSD diagnosis raises numerous challenges. People with DSD have increased risk of malignancy, especially when obesity and, systemic malformations are present; also, psychosocial issues in these children are associated with postpubertal age.

Explaining the complex impact of the Covid-19 pandemic on children with overweight and obesity: a comparative ecological analysis of parents' perceptions in three countries.

BACKGROUND: The Covid-19 pandemic has changed children's eating and physical activity behaviours. These changes have been positive for some households and negative for others, revealing health inequalities that have ramifications for childhood obesity. This study investigates the pandemic's impact on families of children aged 2-6 years with overweight or obesity. METHODS: Drawing on interviews conducted as part of a randomised controlled trial (RCT) for childhood obesity, thematic analysis was used to examine how parents of pre-schoolers perceived changes in their eating, screentime and physical activity behaviours between the first and second waves of Covid-19. Parents (n = 70, representing 68 families) were interviewed twice during a period of 6 months in three countries with markedly different pandemic policies - Sweden, Romania, and Spain. The analysis is informed by Bronfenbrenner's ecological systems theory, which embeds home- and school-based influences within societal and policy contexts. RESULTS: The findings show that, although all participants were recruited from an RCT for families of children with excess weight, they reported different responses to the pandemic's second wave, with some children engaging in healthier eating and physical activity, and others engaging in comfort eating and a more sedentary lifestyle. Differences in children's obesity-related behaviours were closely related to differences in parents' practices, which were, in turn, linked to their emotional and social wellbeing. Notably, across all sites, parents' feeding and physical activity facilitation practices, as well as their emotional and social wellbeing, were embedded in household resilience. In resilient households, where parents had secure housing and employment, they were better able to adapt to the challenges posed by the pandemic, whereas parents who experienced household insecurity found it more difficult to cope. CONCLUSIONS: As the Covid-19 pandemic is turning into a long-term public health challenge, studies that address household resilience are crucial for developing effective prevention and treatment responses to childhood obesity.

Genetic and phenotypic characterization of NKX6-2-related spastic ataxia and hypomyelination.

BACKGROUND AND PURPOSE: Hypomyelinating leukodystrophies are a heterogeneous group of genetic disorders with a wide spectrum of phenotypes and a high rate of genetically unsolved cases. Bi-allelic mutations in NKX6-2 were recently linked to spastic ataxia 8 with hypomyelinating leukodystrophy. METHODS: Using a combination of homozygosity mapping, exome sequencing, and detailed clinical and neuroimaging assessment a series of new NKX6-2 mutations in a multicentre setting is described. Then, all reported NKX6-2 mutations and those identified in this study were combined and an in-depth analysis of NKX6-2-related disease spectrum was provided. RESULTS: Eleven new cases from eight families of different ethnic backgrounds carrying compound heterozygous and homozygous pathogenic variants in NKX6-2 were identified, evidencing a high NKX6-2 mutation burden in the hypomyelinating leukodystrophy disease spectrum. Our data reveal a phenotype spectrum with neonatal onset, global psychomotor delay and worse prognosis at the severe end and a childhood onset with mainly motor phenotype at the milder end. The phenotypic and neuroimaging expression in NKX6-2 is described and it is shown that phenotypes with epilepsy in the absence of overt hypomyelination and diffuse hypomyelination without seizures can occur. CONCLUSIONS: NKX6-2 mutations should be considered in patients with autosomal recessive, very early onset of nystagmus, cerebellar ataxia with hypotonia that rapidly progresses to spasticity, particularly when associated with neuroimaging signs of hypomyelination. Therefore, it is recommended that NXK6-2 should be included in hypomyelinating leukodystrophy and spastic ataxia diagnostic panels.