Heterozygous loss-of-function variants in SPTAN1 cause an early childhood onset distal myopathy.

Purpose: Heterozygous pathogenic variants in SPTAN1 cause a diverse spectrum of neurogenetic disorders ranging from peripheral and central nervous system involvement to complex syndromic presentations. We set out to investigate the role of SPTAN1 in genetically unsolved hereditary myopathies.

Methods: Through international collaboration we identified 14 families with distal weakness and heterozygous SPTAN1 loss-of-function variants.

TBP Repeat Expansion Analysis in Patients Carrying Heterozygous STUB1 Variants.

Background: The cooccurrence of intermediate (40-49 CAG/CAA) TBP repeat expansions with STUB1 variants questions the pathogenicity of monoallelic STUB1 variants in cerebellar ataxia.

Objective: The objective of this study was to describe the phenotypic spectrum of heterozygous STUB1 variants with or without intermediate TBP repeat expansions.

Methods: We determined the presence of TBP repeat expansions and STUB1 variants in six families with cerebellar ataxia.

Long-Term Follow Up in Anti-Contactin-1 Autoimmune Nodopathy.

Objective: To analyze long-term clinical and biomarker features of anti-contactin-1 (CNTN1) autoimmune nodopathy (AN).

Methods: Patients with anti-CNTN1 autoimmune nodopathy detected in our laboratory from which clinical information was available were included. Clinical features and treatment response were retrospectively collected.

Reduction of sacsin levels in peripheral blood mononuclear cells as a diagnostic tool for spastic ataxia of Charlevoix-Saguenay.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay is a rare neurodegenerative disease caused by biallelic variants in the gene encoding for sacsin. More than 200 pathogenic variants have been identified to date, most of which are missense. It is likely that the prevalence of autosomal recessive spastic ataxia of Charlevoix-Saguenay is underestimated due to the lack of an efficient diagnostic tool able to validate variants of uncertain significance.

Overarching pathomechanisms in inherited peripheral neuropathies, spastic paraplegias, and cerebellar ataxias.

International consortia collaborating on the genetics of rare diseases have significantly boosted our understanding of inherited neurological disorders. Historical clinical classification boundaries were drawn between disorders with seemingly different etiologies, such as inherited peripheral neuropathies (IPNs), spastic paraplegias, and cerebellar ataxias. These clinically defined borders are being challenged by the identification of mutations in genes displaying wide phenotypic spectra and by shared pathomechanistic themes, which are valuable indications for therapy development.

Distinct features in adult polyglucosan body disease: a case series.

Adult polyglucosan body disease (APBD) is caused by bi-allelic pathogenic variants in GBE1 and typically shows middle age onset urinary symptoms followed by progressive gait disturbances and possibly cognitive decline. Here we present a Belgian cohort of four patients from three families showing both classical and atypical signs of APBD. By clinical phenotyping, detailed neuroimaging of both central nervous system and skeletal muscle, genetic and biochemical testing, we confront our findings with the classical presentation of adult polyglucosan body disease and emphasize the importance of a multidisciplinary approach when diagnosing these patients.

RFC1 repeat expansions: A recurrent cause of sensory and autonomic neuropathy with cough and ataxia.

Background And Purpose: Ataxia and cough are rare features in hereditary sensory and autonomic neuropathies (HSAN), a group of diseases of mostly unknown genetic cause. Biallelic repeat expansions in RFC1 are associated with cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS). This study aimed to investigate the prevalence of RFC1 repeat expansions in a cohort of HSAN patients.

De Novo and Dominantly Inherited SPTAN1 Mutations Cause Spastic Paraplegia and Cerebellar Ataxia.

Background: Pathogenic variants in SPTAN1 have been linked to a remarkably broad phenotypical spectrum. Clinical presentations include epileptic syndromes, intellectual disability, and hereditary motor neuropathy.

Objectives: We investigated the role of SPTAN1 variants in rare neurological disorders such as ataxia and spastic paraplegia.

Autochthonous Cases of Tick-Borne Encephalitis, Belgium, 2020.

We report 3 confirmed autochthonous tick-borne encephalitis cases in Belgium diagnosed during summer 2020. Clinicians should include this viral infection in the differential diagnosis for patients with etiologically unexplained neurologic manifestations, even for persons without recent travel history.