Am J Med Genet A. 2025 Apr 21:e64091. doi: 10.1002/ajmg.a.64091. Online ahead of print.
ABSTRACT
Lateral meningocele syndrome is a rare skeletal syndrome caused by truncating variants in the final exon of the NOTCH3 gene. It is characterized by multiple lateral meningoceles that may result in neurological sequelae. A wider systemic phenotype has been demonstrated, including musculoskeletal abnormalities, feeding difficulties, structural cardiac and renal anomalies, and facial dysmorphism. We describe the clinical details of a child who was initially diagnosed with Copenhagen syndrome (progressive non-infectious anterior vertebral body fusion), based on radiological findings, in the context of kyphosis and back pain. Later, a novel de novo c.6723_6736del p.(Glu2241AspfsTer8) NOTCH3 variant was identified from the 100,000 Genomes Project, in keeping with a genetic diagnosis of lateral meningocele syndrome. Without the context of additional features that may point toward an underlying syndrome, radiological findings-when reviewed in isolation-may be suggestive of alternate diagnoses. In this case, the radiological finding of anterior vertebral fusion suggested Copenhagen syndrome, whereas the identification of dural ectasia prompted further investigation into Ehlers-Danlos syndrome subtypes. Recognition of dysmorphology prompted wider investigation by Whole Genome Sequencing. Features of lateral meningocele syndrome significantly overlap with those of connective tissue disorders including EDS, Marfan syndrome, and Loeys-Dietz syndrome. We describe the clinical features of the here-reported proband with a novel NOTCH3 variant, and compare the phenotypes of these differential diagnoses.
PMID:40256810 | DOI:10.1002/ajmg.a.64091
