Shreya Goyalpatel1, Neelam Goyal2, May Han2, Jacinda Sampson3
1Los Altos High School, 2Stanford University, 3Stanford
Objective:
To report adult-onset, autosomal dominant leukodystrophy associated with novel LAMA2 nonsense mutation in two sisters presenting with white matter abnormalities in absence of myopathy.
Background:
The LAMA2 gene (chromosome 6q22-q23), encodes for the alpha-2 subunit of laminin-211(merosin), which is expressed in skeletal muscle. Merosin is involved with cell adhesion, cell differentiation, neurite growth, and schwann cell migration. LAMA2 mutations (autosomal recessive) lead to LAMA2-related muscular dystrophy (LAMA2 MD) with varying phenotypic presentation from severe congenital to milder late-onset. White matter abnormalities in children with early onset LAMA2 MD is well appreciated, however, only one case report of LAMA2 mutation mimicking MS exists. LAMA2-mediated leukodystrophy may be related to merosin’s role in the blood brain barrier.
Results:
Case #1: 55 y/o female, history of epilepsy, thyroid cancer, seen for incidental findings of confluent progressive white matter lesions on MRI brain. She had no neurological symptoms and neurological examination including a comprehensive neuropsychological testing was normal.
Case #2: 58 y/o female, history of multiple cancers (thyroid cancer 2006, breast cancer 2006, lung cancer 2021), seen in 2007 for incidental findings of white matter lesions on MRI brain. Laboratory and CSF evaluation negative. Repeat MRI showed progression (see imaging). She had no neurological symptoms, but 3/2022 examination showed increased tone in legs and reduced vibration at toes with absent ankle jerks. Neuropsychiatric testing revealed average cognitive function with deficiency in some functional domains.
Genetic testing in both patients (sisters) showed the same single nucleotide nonsense LAMA2 gene mutation, suggesting pathogenesis.
Conclusions:
We present a case series of two sisters with an atypical presentation of a LAMA2 mutation related disorder: 1) no neuromuscular findings, 2) multiple cancers in the two patients and first degree relatives, and 3) autosomal dominant inheritance pattern. This unique presentation allows us to better understand the variable presentation of LAMA2 caused disorders.