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. 2023 Apr 12;9(3):e200069.
doi: 10.1212/NXG.0000000000200069. eCollection 2023 Jun.

Extension of the Clinicoradiologic Spectrum of Newly Described End-Truncating LAMB1 Variations

Hélène Morel  1 , Laurent Bailly  1 , Cédric Urbanczyk  1 , Dominique Hervé  1 , Stéphane Berroir  1 , Raphaël Le Bouc  1 , Richard Levy  1 , Mylène Meyer  1 , Chaker Aloui  1 , Elisabeth Tournier-Lasserve  1 , Guillaume Mathey  1
Affiliations

Extension of the Clinicoradiologic Spectrum of Newly Described End-Truncating LAMB1 Variations

Hélène Morel et al. Neurol Genet. .

Abstract

Objectives: To refine the clinical spectrum of a very recently identified phenotype associated with LAMB1 end-truncating pathogenic variations.

Methods: Detailed clinical, neuropsychological, and MRI investigation of 6 patients from 2 unrelated families segregating end-truncating LAMB1 variations.

Results: All patients harbored a LAMB1 end-truncating pathogenic variation. The specific association of a hippocampal type episodic memory dysfunction and a diffuse leukoencephalopathy was observed in all 4 patients aged older than 50 years, slightly worsening over time in 2 patients with several years of follow-up. Additional unspecific neurologic symptoms are reported, such as episodes of numbness, language troubles, or faintness in these 4 patients and the 2 younger ones.

Discussion: The association of an extensive leukoencephalopathy with an episodic memory dysfunction of the hippocampal type is strongly suggestive of a LAMB1 end-truncating variation in adults older than 50 years. Early cognitive complaints and imaging abnormalities might exist decades before. Additional transient manifestations can be observed, and this association should lead to LAMB1 screening to avoid unnecessary invasive investigations.

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Conflict of interest statement

H. Morel reports no disclosures relevant to the manuscript; L. Bailly reports no disclosures relevant to the manuscript; C. Urbanczyk reports no disclosures relevant to the manuscript; D. Hervé reports no disclosures relevant to the manuscript; S. Berroir reports no disclosures relevant to the manuscript; R. Le Bouc reports no disclosures relevant to the manuscript; R. Levy reports no disclosures relevant to the manuscript; M. Meyer reports no disclosures relevant to the manuscript; C. Aloui reports no disclosures relevant to the manuscript; E. Tournier-Lasserve reports no disclosures relevant to the manuscript; G. Mathey reports no disclosures relevant to the manuscript. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/NG.

Figures

Figure 1
Figure 1. Genealogical Trees of F1 and F2 Families and Location of the 2 Mutations Identified in LAMB1
(A) Genealogical trees of F1 and F2 families. Square = male; circle = female; diagonal black line = deceased individual; black filled symbol = clinically and MRI-proven affected individual; open symbol = clinically healthy individuals based on family history but no MRI performed; open symbol with a question mark = unknown clinical status; arrow symbol = proband. (B) Schematic representation of LAMB1 protein and location of pathogenic variations identified in F1 (dot) and F2 (triangle). Dark gray box = laminin N-terminal domain; light gray boxes = laminin EGF domains; dashed vertical line = NMD boundary (∼c.5166/p.1722); triangle = pathogenic variation identified if F2 (p.(Lys1708IlefsTer23)), dot = pathogenic variation identified if F1 (p.(Asn1750LysfsTer4)).
Figure 2
Figure 2. Selected Brain MRI Data (Axial Fluid-Attenuated Inversion Recovery Sequences) of Symptomatic Patients
Fluid-Attenuated Inversion Recovery sequence images showing diffuse white matter hyperintensities in all patients. Hyperintensities affect deep white matter, especially the external capsule (except for the youngest patient) and the centrum semiovale. Gyral white matter is also affected in part, although juxtacortical white matter remains spared. No infarcts, lacunar infarcts, microbleed, or hemorrhage was noticed.
See this image and copyright information in PMC

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