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. 2020 Dec;35(12):2343-2347.
doi: 10.1002/mds.28244. Epub 2020 Sep 19.

Paroxysmal Cranial Dyskinesia and Nail-Patella Syndrome Caused by a Novel Variant in the LMX1B Gene

Sara Bech  1 , Annemette Løkkegaard  1 , Troels T Nielsen  2 , Anne Nørremølle  3 , Sabine Grønborg  4   5 , Lis Hasholt  3 , Gudrun K Steffensen  6 , Gabor Graehn  7 , Jess H Olesen  5 , Niels Tommerup  3 , Yuan Mang  3 , Mads Bak  5 , Jørgen E Nielsen  2   3 , Hans Eiberg  3 , Lena E Hjermind  2   3
Affiliations

Paroxysmal Cranial Dyskinesia and Nail-Patella Syndrome Caused by a Novel Variant in the LMX1B Gene

Sara Bech et al. Mov Disord. 2020 Dec.

Abstract

Background: In a Danish family, multiple individuals in five generations present with early-onset paroxysmal cranial dyskinesia, musculoskeletal abnormalities, and kidney dysfunction.

Objective: To demonstrate linkage and to identify the underlying genetic cause of disease.

Methods: Genome-wide single-nucleotide polymorphisms analysis, Sequence-Tagged-Site marker analyses, exome sequencing, and Sanger sequencing were performed.

Results: Linkage analyses identified a candidate locus on chromosome 9. Exome sequencing revealed a novel variant in LMX1B present in all affected individuals, logarithm of the odds (LOD) score of z = 6.54, predicted to be damaging. Nail-patella syndrome (NPS) is caused by pathogenic variants in LMX1B encoding a transcription factor essential to cytoskeletal and kidney growth and dopaminergic and serotonergic network development. NPS is characterized by abnormal musculoskeletal features and kidney dysfunction. Movement disorders have not previously been associated with NPS.

Conclusions: Paroxysmal dyskinesia is a heretofore unrecognized feature of the NPS spectrum. The pathogenic mechanism might relate to aberrant dopaminergic circuits. © 2020 International Parkinson and Movement Disorder Society.

Keywords: dyskinesia; dystonia; nail-patella syndrome; paroxysmal dyskinesia.

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Figures

FIG. 1.
FIG. 1.
Pedigree. All black indicates the presence of nail‐patella syndrome (NPS) musculoskeletal features and paroxysmal dyskinesia (PxD); black and white indicates musculoskeletal phenotype only. Asterisks (*) indicate availability of SNP6.0 data. The haplotypes for Individuals I‐1, I‐2, and II‐6 are inferred.
See this image and copyright information in PMC

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