Background: Genetic testing in cardiomyopathies has a great impact on diagnosis and further management. Considering novel technologies developed for DNA sequencing, it is important to understand the indication and limits of genetic testing available, while taking cost-efficiency into account. Aim: The focus of this review is to summarize the current genetic testing approach in cardiomyopathies in order to determine the best patient pathway in reaching a genetic diagnosis. Methods: For this narrative review, we performed a search of several electronic databases, selected and evaluated relevant manuscripts. Results: Each method of genetic testing in cardiomyopathies was assessed in terms of the diagnosis yield, benefits, limitations and turnaround time. Conclusion: Whether the use of whole exome or genome sequencing can improve the performance of genetic diagnosis in cardiomyopathies over standard custom panels is challenging and needs to be determined in future researches.

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 20102020, 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.

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.

Introduction. The Antley-Bixler syndrome (ABS) is an extremely rare syndrome characterized by congenital craniosynostosis and radiohumeral synostosis. Many patients demonstrate defects in steroidogenesis and disturbances of sexual development.Aim: To present the first documented case of a Romanian patient with ABS.Material and Methods. Alexandru, a 3 year old child, was referred to our department for elucidating a complex malformative syndrome that consisted of ambiguous genitalia and skeletal anomalies. We performed a complete assessment that ranged from obtaining a detailed medical history to gene sequencing.The hospital's Ethical Committy gave the authors its approval for using the medical data concerning the case, after the parents signed an informed consent.Results. Medical history. We note 4 previous admissions to our hospital during which efforts were made to diagnose the child's disorder of sexual development. At 3 months Edwards syndrome was suspected, which was later infirmed. During the third and fourth admission (8 months, 10 months respectively) the suspicion of congenital adrenal hyperplasia (CAR) was raised and then confirmed (impaired steroidogenesis, 46 XX karyotype). The patient was lost to follow-up since then, probably due to the parents' inability to cope with the implications of their child's condition.

Aims. To provide growth references for school-aged children in western Romania, to compare them with other national and international growth charts and evaluate the prevalence of overweight and obesity.Methods. A total of 3731 children, aged 7-19 years, from Timis county, were examined by medical students, between February 2010-June 2011. Growth references for height, weight, and body mass index (BMI) were constructed with LMS method and LMSChartMaker software. The Romanian 3rd, 50th and 95th percentile for height and BMI were compared with national and international growth references. The prevalence of overweight and obesity was determined with IOTF definition.Results. Crude and smoothed percentiles for weight, height and 13M1 were shown for this population. The comparison provided data regarding the variation of growth models in different populations. Our results demonstrated a high prevalence of overweight (18.2%) and obesity (7.2%) in our population, higher in boys versus girls.Conclusions. Our study constructed growth references for a Romanian population. The comparison with other growth references reflected the regional differences in growth patterns between populations.

Background. The increase in prevalence of obesity in children is well known worldwide, with important implications for health.Aim. To evaluate the growth patterns of normal weight, overweight, obese and underweight schoolchildren from western Romania,. in order to understand how body mass is related to height gain.Material and method. A total of 3626 children aged 7-18 years, were examined, between February 2010-June 2011. Children were classified as normal weight, underweight, overweight and obese, using IOTF criteria.Results. We present the growth curves in regard to BMI class and the comparison of the 50th percentile of each BM! class, in boys and girls separately. The period of significant height difference/year at the 50th percentile for each BMI class indicates that overweight and obese boys have important height gain between 11-14 years, while for underweight boys it is constant between 11-18 years. In overweight and obese girls, an important height difference/year is observed between 7-11 years, while in underweight group it is seen between 10-13 years.Conclusions. In boys, increased BMI leads to taller young stature, delayed growth spurt, but similar height at age of 18 years, while in the underweight group we observed a prolonged growth spurt with increased height at 18 years. Increased BMI, in girls, resulted in early growth spurt and similar height at 18 years when compared to normal weight peers. Final height was independent of BMI in both girls and boys.