Case Report: Diffuse Polymicrogyria Associated With a Novel ADGRG1 Variant
Fábio Carneiro1, Júlia Duarte2, Francisco Laranjeira3
1Neurology Department, Hospital Garcia de Orta, Almada, Portugal.
Frontiers in Pediatrics
|September 13, 2021
Summary
A novel ADGRG1 gene variant causes diffuse polymicrogyria and severe developmental delay, challenging previous understandings of this condition. This finding expands the known spectrum of ADGRG1-related brain malformations.
Area of Science:
- Genetics
- Neuroscience
- Developmental Biology
Background:
- Pathogenic variants in the ADGRG1 gene are linked to bilateral frontoparietal polymicrogyria.
- This condition is characterized by specific radiological features including an anterior-posterior gradient of polymicrogyria, pontine and cerebellar hypoplasia, and white matter abnormalities.
Observation:
- A patient presented with motor delay, esotropia, hypotonia, and refractory epilepsy.
- Clinical assessment revealed a severe motor and cognitive phenotype, with failure to acquire head control, sitting, or language by age 12.
- Brain MRI showed diffuse polymicrogyria without an anterior-posterior gradient, diffuse hypomyelination, and pontine/cerebellar hypoplasia.
Findings:
- Genetic analysis identified a novel, unreported homozygous ADGRG1 nonsense variant (dbSNP rs746634404).
- This variant was present in the heterozygous state in both parents, indicating autosomal recessive inheritance.
- The identified variant is associated with a diffuse polymicrogyria pattern and a severe clinical presentation.
Implications:
- This case expands the known phenotypic spectrum associated with ADGRG1 pathogenic variants.
- It highlights the potential for atypical presentations, including the absence of an anterior-posterior gradient in polymicrogyria.
- The findings suggest a significant clinico-anatomical overlap between different polymicrogyria syndromes, emphasizing the importance of genetic analysis in diagnosis.
