A descriptive genomic observation of a teenage boy presenting with epilepsy, intellectual disability, and mild facial dysmorphism, found to carry a 48.55 kb 2q13 microdeletion restricted to the BUB1 locus alongside a concurrent 11q21 microdeletion is presented.
Abstract
Background: The chromosomal microdeletion syndrome 2q13 is characterized by craniofacial dysmorphism, developmental delay, intellectual disability, autism spectrum disorder, attention deficit hyperactivity disorder, cardiac abnormalities, and seizures. Case Presentation: In this study, we present a descriptive genomic observation of a teenage boy presenting with epilepsy, intellectual disability, and mild facial dysmorphism, found to carry a 48.55 kb 2q13 microdeletion restricted to the BUB1 locus alongside a concurrent 11q21 microdeletion. While his clinical features overlap with the 2q13 microdeletion spectrum, the exact pathogenic contribution of each variant remains a subject of hypothesis due to the lack of parental inheritance data. Conclusions: Further research is necessary to ascertain the impact of the concurrence of small deletions on these disorders. This case underscores the clinical complexity introduced by compound minor copy number variations and emphasizes the value of molecular cytogenetics in evaluating idiopathic neurodevelopmental disorders.
Background: Epilepsy and behavioral disorders in children can result from various genetic etiologies. We report the case of a child with refractory epilepsy and behavioral disturbances in whom two rare variants were identified in the SLC2A1 and SMC1A genes. This case highlights the importance and challenges of early molecular diagnosis in resource-limited African settings. Case Presentation: A male child presented with early-onset epilepsy and significant behavioral disturbances. Neurological examination showed no malformations. Brain MRI was normal. Sleep EEG revealed no interictal epileptiform activity. Psychomotor assessment indicated hyperactivity, attentional deficits, fine and gross motor difficulties, and opposition to limits. Initial developmental screening was performed using the Denver Developmental Screening Test II, which showed mild delay in fine motor coordination and expressive language. A subsequent comprehensive evaluation using the Bayley Scales of Infant and Toddler Development, 3rd edition, confirmed a global psychomotor delay predominantly affecting coordination and attention. Genetic analysis from a buccal swab using targeted next-generation sequencing revealed two heterozygous rare variants: SLC2A1 c.580_585del (p. Phe194_Ile195del) and SMC1A c.2414A>G. These variants have not been previously reported in African literature. The patient received adapted antiepileptic therapy and multidisciplinary follow-up. Conclusion: This case illustrates the exceptional coexistence of SLC2A1 and SMC1A variants and underlines the value of early molecular diagnosis even in resource-limited contexts, to guide personalized management.
Kouakou Kouamé Cyprien, Doumbia-Ouattara Mariam, Dainguy Marie Evelyne et al.· Journal of Pediatric Genetic...· 0 citations
This study expands the mutational landscape of JS in the Iranian population and underscores the utility of WES as a first-tier diagnostic tool for JS and related ciliopathies.
Sheyda Khalilian, Mohadeseh Fathi, Zahra Farbood et al.· Molecular Genetics and Metab...· 0 citations
This case expands the clinical spectrum associated with RFX3 variants, supporting a potential role in IESS and early neurodevelopmental disruption, and highlights the relevance of including RFX3 in the genetic evaluation of patients with IESS and co-occurring neurodevelopmental disorders.
Graziana Ceraolo, Giulia Spoto, M. Trivisano et al.· International Journal of Mol...· 0 citations
KBG syndrome is a rare autosomal dominant neurodevelopmental disorder caused by pathogenic variants
in the ANKRD11 gene. The clinical presentation is highly variable and may include characteristic craniofacial
features, developmental delay, learning disabilities, behavioral abnormalities, and growth impairment. Here
we describe a Lebanese female patient who was followed for 11 years because of failure to thrive,
developmental delay, attention deficit, behavioral difficulties, and persistent learning disabilities. Longitudinal follow-up documented gradual neurocognitive improvement with multidisciplinary interventions and
pharmacological treatment for attention and behavioral difficulties. Whole Exome Sequencing (WES),
performed at the age of 11 years, identified a novel heterozygous frameshift pathogenic variant in the
ANKRD11 gene (p.Tyr808fs), confirming the diagnosis of KBG syndrome. To our knowledge, this is the first
reported Lebanese patient carrying this specific ANKRD11 variant. This case expands the molecular
spectrum of KBG syndrome and highlights the importance of genomic testing in children presenting with
developmental delay, learning difficulties, and subtle dysmorphic features, particularly when the diagnosis
remains uncertain during early childhood.
The 15q11.2 microdeletion is a chromosomal condition associated with a broad epileptic phenotype. It is differentiated from Angelman syndrome, which is typically a larger maternal deletion in an overlapping area. We describe a patient with a 15q11.2 microdeletion that has clinical and EEG biomarker features similar to those seen in Angelman syndrome. The patient was found to have a maternally inherited, likely pathogenic 258 kb deletion at 15q11.2. Novel electroclinical features associated with this finding included myoclonic absence seizures and other EEG findings consistent with the syndrome of Epilepsy with Myoclonic absences. The 15q11.2 microdeletion syndrome has a broad phenotype, and accuracy of diagnosis appears variable and inconsistent. EEG and knowledge of unique biomarkers may be a tool that can further refine genetic diagnosis.
Clinical heterogeneity among children with NRXN1 deletions illustrates clinical heterogeneity among children with autism spectrum disorder and supports the need for larger studies to better define genotype-phenotype relationships.
Samira Said AlHousni, A. Idris, Watfa Al-Mamari et al.· Sultan Qaboos University Med...· 0 citations