Expanding the Phenotypic Spectrum of DPH2 -Related Disorder

Area of Science:

• Genetics
• Neurology
• Pediatrics

Background:

• Biallelic variants in DPH2 are associated with diphthamide deficiency syndrome-2.
• This syndrome presents with developmental delay, short stature, dysmorphic features, and sparse hair.

Purpose of the Study:

• To report a novel case of DPH2-related disorder in an Indian child.
• To describe the clinical, neuroimaging, and electroencephalogram findings.
• To expand the phenotypic spectrum of DPH2-related disorders.

Main Methods:

• Clinical case description.
• Genetic analysis identifying a biallelic loss-of-function variant (p.Arg477*) in DPH2.
• Neuroimaging (MRI) and electroencephalogram (EEG) analysis.

Main Results:

• The patient presented with developmental delay, failure to thrive, sparse hair, seizures, proportionate short stature, dysmorphism, and hypotonia.
• Neuroimaging revealed cerebral atrophy, periventricular white matter hyperintensities, and prominent subarachnoid spaces.
• EEG showed findings suggestive of modified hypsarrhythmia.

Conclusions:

• This case expands the known phenotype of DPH2-related disorders to include seizures and specific neuroimaging abnormalities.
• This is the third reported case globally and the first from India, highlighting the importance of DPH2 in neurodevelopmental disorders.