LAMB1-associated leukoencephalopathy: a continuum from a prenatal, recessive syndrome to a dominant, adult-onset disorder

Area of Science:

• Genetics
• Neurology
• Biochemistry

Background:

• Leukodystrophies are a group of inherited white matter disorders.
• The LAMB1 gene plays a role in brain development and function.
• Genetic variants in LAMB1 can lead to diverse neurological phenotypes.

Purpose of the Study:

• To investigate the genetic basis of leukoencephalopathy in a pediatric patient with focal seizures.
• To analyze the clinical and neuroimaging findings associated with LAMB1 variants.
• To understand the phenotypic spectrum of LAMB1-related leukoencephalopathies.

Main Methods:

• Clinical assessment and neuroimaging (MRI) of the patient.
• Genetic analysis using a leukodystrophy gene panel.
• Segregation analysis to determine inheritance patterns of identified variants.
• Literature review of LAMB1-related conditions.

Main Results:

• The patient presented with focal seizures and bilateral, symmetrical white matter hyperintensities on MRI.
• Compound heterozygous variants (c.3659_3660delTG and c.2942A>T) in the LAMB1 gene were identified, inherited from both parents.
• Published data show a broad phenotype for biallelic LAMB1 variants and overlapping features with monoallelic variants.

Conclusions:

• This case expands the understanding of LAMB1-related leukoencephalopathies, demonstrating a pediatric presentation with compound heterozygous variants.
• The findings underscore the complexity of LAMB1-related disorders, with both recessive and dominant forms exhibiting overlapping clinical and imaging features.
• Comprehensive literature review is crucial for interpreting genetic findings and understanding conditions with shared genetic etiology.