Neonatal myoclonus in Bryant-Li-Bhoj syndrome associated with a novel H3F3A variant

Area of Science:

• Genetics
• Neurodevelopmental Disorders
• Histone Biology

Background:

• Bryant-Li-Bhoj syndrome (BLBS) is a rare genetic disorder linked to germline variants in H3F3A and H3F3B genes, which encode histone H3.3.
• The syndrome is primarily characterized by developmental delay, intellectual disability, failure to thrive, abnormal muscle tone, and distinctive facial features.

Purpose of the Study:

• To report a novel H3F3A variant associated with BLBS.
• To describe an expanded phenotypic spectrum of BLBS, including previously unrecognized symptoms.

Main Methods:

• Case report of a Japanese patient with BLBS.
• Genetic sequencing to identify variants in H3F3A and H3F3B.
• Clinical evaluation and phenotypic characterization.

Main Results:

• Identification of a novel heterozygous p.A48G variant in the H3F3A gene.
• The patient presented with classic BLBS features and newly observed neonatal myoclonus.
• This finding expands the known clinical manifestations of BLBS.

Conclusions:

• The p.A48G variant in H3F3A is associated with BLBS.
• Neonatal myoclonus represents a previously unrecognized symptom of BLBS.
• This case broadens the understanding of the phenotypic variability in BLBS.