RESUMO
OBJECTIVES: To determine the prevalence of tuberous sclerosis complex (TSC) in the paediatric Saudi population and to characterise the range of clinical symptoms, neurocutaneous findings, neuroimaging results, and complications of the disease. METHODS: A total of 61 genetically confirmed TSC patients from the National Guard Health Affairs (NGHA) in Saudi Arabia were the subject of this retrospective descriptive analysis. The data were presented using descriptive measures. RESULTS: The mean age at diagnosis was found to be 4.9 years. Subependymal nodules (86.9%), numerous cortical tubers and/or radial migration lines (63.9%), and hypomelanotic macules (63.9%) were the 3 most common significant criteria. The vast majority (86.9%) of those diagnosed had epilepsy, of which 50% were considered medically intractable. Nearly half of our subjects underwent genetic testing, which revealed that TSC2 predominated over TSC1. Symptoms of Tuberous Sclerosis Complex-Associated Neuropsychiatric Disorders (TAND) were present in 66.7% of TSC1 patients and 73.9% of TSC2 patients. CONCLUSION: The findings of this study demonstrate that the clinical spectrum of TSC among Saudi children is consistent with the body of existing literature. The TSC2 was more prevalent than TSC1. The most frequent signs were cutaneous and neurological. Monitoring TSC patients regularly is crucial to identify any issues as soon as possible.
Assuntos
Proteína 2 do Complexo Esclerose Tuberosa , Esclerose Tuberosa , Humanos , Esclerose Tuberosa/epidemiologia , Esclerose Tuberosa/complicações , Arábia Saudita/epidemiologia , Feminino , Masculino , Pré-Escolar , Criança , Proteína 2 do Complexo Esclerose Tuberosa/genética , Estudos Retrospectivos , Lactente , Adolescente , Proteína 1 do Complexo Esclerose Tuberosa/genética , Proteínas Supressoras de Tumor/genética , Epilepsia/epidemiologia , Epilepsia/etiologia , PrevalênciaRESUMO
Wiedemann-Rautenstrauch Syndrome (WRS; MIM 264090) is an extremely rare and highly heterogeneous syndrome that is inherited in a recessive fashion. The patients have hallmark features such as prenatal and postnatal growth retardation, short stature, a progeroid appearance, hypotonia, facial dysmorphology, hypomyelination leukodystrophy, and mental impairment. Biallelic disease-causing variants in the RNA polymerase III subunit A (POLR3A) have been associated with WRS. Here, we report the first identified cases of WRS syndrome with novel phenotypes in three consanguineous families (two Omani and one Saudi) characterized by biallelic variants in POLR3A. Using whole-exome sequencing, we identified one novel homozygous missense variant (NM_007055: c.2456C>T; p. Pro819Leu) in two Omani families and one novel homozygous variant (c.1895G>T; p Cys632Phe) in Saudi family that segregates with the disease in the POLR3A gene. In silico homology modeling of wild-type and mutated proteins revealed a substantial change in the structure and stability of both proteins, demonstrating a possible effect on function. By identifying the homozygous variants in the exon 14 and 18 of the POLR3A gene, our findings will contribute to a better understanding of the phenotype-genotype relationship and molecular etiology of WRS syndrome.
Assuntos
Progéria , Gravidez , Feminino , Humanos , Fenótipo , Progéria/genética , Retardo do Crescimento Fetal/genética , Mutação de Sentido Incorreto , Síndrome , RNA Polimerase III/genéticaRESUMO
Purpose: The aim of this manuscript was to assess the epidemiology and clinical features of Neurofibromatosis type 1 (NF-1) based on the newly published revised NF-1 diagnostic criteria and to evaluate complications of NF-1 including neurodevelopmental disorders. Patients and methods: A retrospective cross-sectional observational study was conducted in the Ministry of National Guard Health Affairs (MNGHA) healthcare organization branches including four tertiary hospitals and 51 primary health care centers in different regions in Saudi Arabia. This study included all patients diagnosed with NF1 using the revised NIH diagnostic criteria published in 2021 that were registered at the electronic medical records (EMR) from 2015 to 2021. Results: A total of 184 patients fulfilled the diagnostic criteria and were included in this study. The median age at diagnosis was 11 years (IQR: 4.00-20.25). The most encountered diagnostic criteria in this study were Café-au-lait macules (85.3%), and (42.9%) were found to have two or more neurofibromas with plexiform neurofibroma being the most common subtype (23.36%), approximately (36.4%) of the patient with optic pathway glioma. Nearby (26.6%) of the patients displayed different type of tumors. Iris Lisch nodules were presented in 36.4% of patients at a median age of 12 years (IQR: 9.0-21.8). Cardiovascular abnormality was encountered in 9.8% of the patients. Around 27.7% of the patients reported headache and 11.4% of the patient suffered from different type of epilepsy. Besides, 10.5% of the patients had intellectual disability, 33.8% suffered from communication disorders, and 4.9% patients had ADHD. Conclusion: The results of this study will enable practitioners to adopt a more holistic approach and prioritize numerous attributes, which they can subsequently incorporate into their therapeutic methodologies. Furthermore, the identification of these attributes will facilitate an expeditious and accurate diagnosis. Hence, the implementation of intervention during its nascent phase may result in a more advantageous consequence.
RESUMO
Congenital disorders of glycosylation (CDG) are a group of more than 100 rare genetic disorders characterized by impaired glycosylation of proteins and lipids. The clinical presentation of CDG varies tremendously, from single-organ to multi-organ involvement and from prenatal death to a normal adult phenotype. In this case study, we report a large consanguineous family with multiple children suffering from cerebral palsy, seizure, developmental and epileptic encephalopathy, and global developmental delay. Whole-exome sequencing (WES) analysis revealed a homozygous variant in the UDP-glucose dehydrogenase (UGDH) gene (c.950G>A; p.R317Q) which segregates with the familial phenotype with a plausible autosomal recessive mode of inheritance, indicating a potential disease-causing association. The UGDH gene encodes the UDP-glucose dehydrogenase, a key enzyme in the synthesis of specific extracellular matrix constituents (proteoglycans and glycolipids) involved in neural migration and connectivity during early brain development. Many pathogenic mutations of UGDH have been reported in recent literature works. However, the variant identified in this study has been observed only in the Saudi population (13 families) and not in any other ethnic background, suggesting that it may be an ancient founder mutation.