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Genetic Insights into Snijders Blok Campeau Syndrome: A Case Study of a Homozygous CHD3 Variant and Comorbidities 

Clinical Genetics and Therapeutics
  • Primary Categories:
    • Clinical- Pediatric
  • Secondary Categories:
    • Clinical- Pediatric
Introduction
Snijders Blok Campeau syndrome (SNIBCPS) is a rare, recently described, neurodevelopmental disorder linked to heterozygous pathogenic variants in the CHD3 gene, which plays a crucial role in chromatin remodeling and gene expression. Patients typically present with developmental delays, speech difficulties, behavioral disorders, intellectual disabilities, and distinctive facial features including macrocephaly, hypertelorism, spare eyebrows, broad forehead, prominent nose, and pointed chin. With only 60 or so cases reported thus far, the full phenotypic spectrum associated with SNIBCPS remains poorly defined. Furthermore, the phenotype of homozygous CHD3 pathogenic variants has not been characterized. Previously, only a single pair of siblings has been reported with homozygous CHD3 in frame duplication pathogenic variants presenting with severe intellectual disability, skeletal abnormalities, and much more striking facial dysmorphism compared to heterozygotes. This report discusses a novel homozygous variant in CHD3 identified in a young patient, alongside additional genetic diagnoses that contribute to a complex clinical picture.

 

Case Presentation
A 23-month-old female was referred to our clinic for establishment of biochemical and pediatric genetic care due to a complex medical history, which included multiple genetic diagnoses: transcobalamin receptor deficiency, SNIBCPS, and DFNB106 related hearing loss. The patient had initially presented in the NICU with a positive newborn screen and dysmorphic features.

Clinically, the patient presented with profound developmental delays, particularly in language acquisition and motor skills. Hypotonia was observed, along with facial features characteristic of SNIBCPS including hypertelorism, midfacial hypoplasia, sparse eyebrows, a high, broad forehead, a wide or prominent nose, a thin upper lip, and low-set, posteriorly rotated ears.

 

Diagnostic Workup
Prior genetic testing included chromosomal microarray, MMA/HCU genetic panel, and exome sequencing.

Discussion
This case represents one of few documented instances of a patient with SNIBCPS harboring homozygous variants in CHD3. This patient presented with a more severe neurodevelopmental phenotype than has been reported in heterozygous SNIBCPS patients with development approximating that of a 4-month-old at nearly 3 years old (most recent visit). This is even more severe than the reported more severe neurodevelopmental phenotype of the two siblings also with homozygous CHD3 variants. The combination of the additional diagnoses of transcobalamin receptor deficiency and DFNB106 hearing loss complicates the clinical presentation. Understanding the implications of these findings could enhance knowledge of SNIBCPS and its associated phenotypes.

Conclusion
The identification of the homozygous CHD3 variant offers a unique opportunity to further delineate the spectrum of CHD3-related disorders

Agenda

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