Aug 2026· Scholars Journal of Medical Case Reports· 0 citations
TL;DR
This case shows that a well-characterized clinical gestalt remains sufficient to diagnose Kabuki syndrome despite negative first-line genetic testing, and that residual possibilities are shown.
Abstract
Background: Kabuki syndrome is a rare multisystem neurodevelopmental disorder usually caused by pathogenic KMT2D or KDM6A variants, although a substantial minority of clinically typical patients remain molecularly unresolved. Autism spectrum disorder (ASD) has been reported in this population, but its prevalence and relationship to genotype remain poorly characterized. Case Presentation: We report a 12-year-old Moroccan boy, born to consanguineous parents, referred for severe behavioral disturbances including psychomotor hyperactivity, self-injurious behavior, and marked language delay. Physical examination showed characteristic craniofacial dysmorphism, long palpebral fissures with eversion of the lateral lower eyelids, blue sclerae, broad arched eyebrows, a depressed nasal tip, and a high-arched palate, together with microcephaly, postnatal growth restriction, infantile hypotonia, a waddling gait, and possible scoliosis, fulfilling international consensus criteria on dysmorphology, growth restriction, hypotonia, and musculoskeletal abnormalities for a clinical diagnosis of Kabuki syndrome. He also presented with severe ASD, attention-deficit/hyperactivity disorder, intellectual developmental disorder, and generalized epilepsy, established according to DSM5 criteria. Whole-exome sequencing identified no pathogenic variant in KMT2D or KDM6A, but revealed a heterozygous variant of uncertain significance in YWHAG (NM_012479.3:c.340G>A; p.Glu114Lys), a gene associated with developmental and epileptic encephalopathy. Pharmacological management included extended-release methylphenidate, which was discontinued because of paradoxical worsening of hyperactivity, followed by low-dose aripiprazole, which improved self-injurious behavior and agitation but caused a persistent tremor. Conclusions: This case shows that a well-characterized clinical gestalt remains sufficient to diagnose Kabuki syndrome despite negative first-line genetic testing, and that residual possibilities
Abstract Background Kabuki syndrome (KS) is a multiple malformation syndrome characterized by distinctive facial features (long palpebral fissures; eversion of the lower lateral eyelid; arched eyebrows with sparse or dispersed lateral one-third; depressed nasal tip; and large, prominent ears), intellectual disability, and postnatal growth deficiency. This condition is caused by pathogenic mutations in either KMT2D (autosomal dominant) or KMD6A (X-linked dominant) and generally occurs as a de novo mutation. To date, KS has been diagnosed only in 350 patients worldwide. The prevalence of Autism Spectrum Disorder (ASD) has been reported to be 1 in 88 individuals. In the literature, there are a few studies reporting patients having KS with ASD. The random comorbidity of these two disorders in our patient was thought to be interesting in terms of possible common etiologic features and gene association. Aims & Objectives - To report a rare case of co-occurrence of Kabuki syndrome and Autism Spectrum Disorder in a 12-year-old boy with severe behavioral and neurodevelopmental impairment. -To discuss the potential shared genetic and etiological mechanisms between Kabuki syndrome and Autism Spectrum Disorder, and to highlight the importance of early multidisciplinary assessment in such complex neurodevelopmental disorders. Method: Descriptive study of a clinical case Our patient is a 12-year-old boy, was brought by his mother in 2023, with complaints of no speech, hyperactivity, temper tantrums, self-injury, and impaired social interaction. He is originally from Errachidia in the south-eastern region of Morocco. He is born to first-degree consanguineous parents. The pregnancy was well followed with no complications. Delivery was a medically assisted vaginal birth, with a birth weight of 3000 g and a history of delayed crying at birth. Psychomotor development was marked by a delay in the acquisition of walking and language. Results We determined the lack of speech and eye contact, stereotypical behavior, and impaired social interaction and diagnosed him with autism, severe mental retardation, attention-deficit/hyperactivity disorder (ADHD) via a psychiatric assessment. In addition to a kabuki syndrome and idiopathic generalized epilepsy, that were diagnosed in the pediatrician department. The patient presents an uncertain significance variant on YWHAG that could be related to his clinical phenotype. Discussion & Conclusions Our case is a new example of the coexistence of KS and ASD in addition to the very few cases in the literature, and that could provide opportunities for understanding the genetic etiology of ASD and new scope in terms of novel treatment approaches.
M. Nokrou, S. Bounouh, Z. Maataoui et al.· International Journal of Neu...· 0 citations
Williams syndrome is a rare multisystem genetic disorder caused by a microdeletion at chromosome 7q11.23 involving the ELN gene. It is characterized by distinctive facial features, cardiovascular abnormalities, developmental delay, endocrine disturbances, and a characteristic hypersocial behavioral profile. We report a 7-year-old girl with genetically confirmed Williams syndrome who presented with urinary tract infection. She had been diagnosed at 1 year of age after recognition of dysmorphic features and congenital cardiac disease, followed by confirmation by chromosome analysis and fluorescence in situ hybridization. Clinical findings included depressed nasal bridge, posteriorly rotated ears, long philtrum, retrognathia, mild pectus deformity, deep-set nails, and mild muscular ventricular septal defect. At follow-up, she had typical “elfin” facies and an unusually friendly personality. This case highlights the importance of early recognition and long-term multidisciplinary follow-up, including cardiovascular, developmental, behavioral, metabolic, renal, hearing, and visual surveillance.
Nooreen, Nagamani Kulkarni, Shivakumar Indi et al.· International Journal of Con...· 0 citations
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 proband, despite carrying a truncating variant, presented without classic digital anomalies or ocular involvement, underscoring that even loss-of-function alleles can produce atypical CSS4 phenotypes.
Xiu-Ling Chen, J. Dumbuya, Jing Qi· Frontiers in Genetics· 0 citations
This Saudi case series adds to the growing evidence of clinical heterogeneity in KBGS, suggesting possible underrecognized systemic involvement and cautious interpretation is required given the small sample size.
Mai S. Labani, Z. Rahbeeni· Frontiers in Pediatrics· 0 citations
A child with refractory epilepsy and behavioral disturbances in whom two rare variants were identified in the SLC2A1 and SMC1A genes 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
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