Aug 2026· Journal of Child Neurology· pp.
8830738261474029
· 0 citations· 6 references
Medicine
TL;DR
This case broadens the mutational spectrum of YIF1B-related disease and highlights the distinctive clinical pattern of KABAMAS, with an 11-month-old Turkish girl with profound developmental delay, absent head control, poor feeding, laryngomalacia and cortical visual impairment.
Abstract
BackgroundKaya-Barakat-Masson syndrome (KABAMAS) is a recently described autosomal recessive neurodevelopmental disorder caused by biallelic pathogenic variants in YIF1B, a gene crucial for trafficking between the endoplasmic reticulum and the Golgi apparatus. Disruption of this pathway leads to Golgi disorganization and neuronal dysfunction, resulting in severe developmental delay, visual impairment, and progressive spasticity.Case PresentationWe report an 11-month-old Turkish girl with profound developmental delay, absent head control, poor feeding, laryngomalacia and cortical visual impairment. Brain magnetic resonance imaging (MRI) revealed corpus callosum thinning and mild ventriculomegaly. Comprehensive metabolic investigations were unrevealing. Whole exome sequencing analysis identified a novel homozygous YIF1B frameshift variant, c.440_441delinsA (p.Ala147Aspfs*51), predicted to cause loss of function.ConclusionThis case broadens the mutational spectrum of YIF1B-related disease and highlights the distinctive clinical pattern of KABAMAS. Recognition of the combination of developmental delay, cortical visual loss, and normal metabolic studies should prompt early genetic analysis. Timely molecular diagnosis enables accurate counseling and multidisciplinary management for affected families.
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André Luiz Santos Pessoa, T. Guimarães, Diego de Castro Dos Santos et al.· Movement Disorders Clinical...· 0 citations
Findings support a dose-dependent SLC20A2 disease spectrum and expand the phenotype associated with biallelic loss of function from primary brain calcification toward severe early-onset neurodevelopmental disorder with prominent vascular and leptomeningeal calcification.
Mehmet Burak Mutlu, Abdullah Sezer, Elif Özdemir et al.· Journal of Human Genetics· 0 citations
The novel NR2F1 variant was classified as likely pathogenic according to ACMG guidelines, confirming the diagnosis of BBSOAS and the ARF3 variant, identified as a secondary finding of uncertain clinical significance, is unlikely to account for the patient's phenotype.
Sina Babaei, Haneieh Honarmand, Mortaza Bonyadi et al.· Molecular Biology Reports· 0 citations
A 9-year-old male patient presenting with developmental delay, behavioral abnormalities, dysmorphic facial features, epilepsy, and congenital cardiac anomalies is reported, highlighting the importance of detailed neurological, electroencephalographic, cardiac, and genetic evaluation in patients with suspected DESSH.
Burak Yavuz, Soner Uzun, Ayhan Kütükçü et al.· American Journal of Medical...· 0 citations
The LAMB1 gene encodes the laminin β1 chain, an essential component of the pial basement membrane required for neural morphogenesis. While biallelic LAMB1 mutations typically result in cobblestone lissencephaly and brainstem abnormalities, we report an extreme, lethal syndromic phenotype that significantly expands the gene's known clinical spectrum. Through genomic sequencing of a 36-week stillborn male fetus from consanguineous parents, we identified a novel homozygous frameshift variant in LAMB1 (NM_002291.3:c.3330dup, p.Gly1111Argfs*23). This fetus exhibited severe growth restriction and a massive occipital meningoencephalocele, alongside pansutural craniosynostosis and an underdeveloped cranial base. Multi-system anomalies included gallbladder agenesis and abnormal lung lobation, alongside secondary endocrine failure and placental vascular defects. This report includes a systematic review of 23 confirmed cases, proposing a 4-category phenotypic classification that positions this case as a lethal extreme. Mechanistically, we propose that this loss-of-function variant impairs integrin-β1-mediated mechanotransduction during human neural tube closure, thereby disrupting the extracellular matrix-planar cell polarity axis. Under this mechanism, the primary encephalocele drives downstream pansutural craniosynostosis by reducing intracranial pressure, and endocrine failure by disrupting the hypothalamo-hypophyso-adrenal axis. Ultimately, these findings highlight LAMB1 as an essential, non-redundant scaffold required for both neural architecture and systemic visceral morphogenesis.
S. Darouich, Samia Darouich, Ahmed Khemiri et al.· Pediatric and Developmental...· 0 citations
Pelizaeus-Merzbacher-like disease type 1 (PMLD1), also known as hypomyelinating dystrophy 2, is a typical slowly progressive hypomyelinating leukodystrophy (HLD) that manifests in the neonatal period or early infancy. In humans, PMLD1 is inherited as an autosomal recessive trait, with genetic variants identified in the gap junction protein gamma 2 (GJC2) gene. Six juvenile-age Toy Poodle dogs exhibited coarse, vertical head and trunk tremors from immediately after birth. Conventional magnetic resonance imaging revealed uniform signal hyperintensities throughout the subcortical white matter in all dogs. All dogs were euthanized. Subsequent histopathological examination revealed vacuolar changes and demyelination in the cerebral and cerebellar white matter, leading to a diagnosis of HLD. Genetic analysis of five affected dogs identified a shared homozygous 14-base pair deletion in the GJC2 gene, XM_038556433.1:c.920_933del. To the best of our knowledge, this is the first report of a pathogenic GJC2 variant in dogs or any other domestic animal species. The results will enable genetic testing and provide a spontaneous large animal model for the homologous human disease.
Yuki Hajiri, Hiroshi Ueno, Gaku Tahara et al.· Journal of Veterinary Medica...· 0 citations