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

A 1 year 11 months-old female patient displayed focal seizures symptoms with good response to oxcarbazepine. Her brain magnetic resonance imaging (MRI) showed white-matter, bilateral and symmetrical hyperintense foci in periventricular parietal and frontal regions with U-fiber sparing. A gene panel requested for the study of leukodystrophies and subsequent segregation reported compound heterozygous variants in LAMB1 gene: c.3659_3660delTG (p.Val1220Glyfs*31), maternally inherited, and c.2942 A > T (p.Asn981Ile), paternally inherited. Published cases with biallelic, loss-of-function LAMB1 variants displayed a broad phenotype that depends on the deleteriousness of the variants, ranging from mildly affected individuals to severely affected ones with multiple other anomalies. Also, monoallelic, presumably toxic gain-of-function LAMB1 variants can also cause leukoencephalopathy but whose onset of manifestations is in adulthood. The cases affected by the dominant condition also exhibit a broad range of manifestations and brain imaging anomalies, some of them overlap to those seen in the recessive LAMB1-related leukoencephalopathy. This work unveils the relevance of performing a comprehensive literature review for a better comprehension of overlapping conditions caused by variants in the same gene.