Pathogenic variants in three families with distal muscle involvement.

Three families suspected of distal hereditary motor neuropathy underwent genetic screening with the aim to identify the molecular defect underlying the disease. The description of the identification reflects the shift in molecular diagnostics that was made during the last decades. Our candidate gene approach yielded a known pathogenic variant in BSCL2 (p.Asn88Ser) in one family, and via a CMT-capture, in HSPB1 (p.Arg127Trp), in addition to five other variations in Charcot-Marie-Tooth-related genes in the proband of the second family. In the third family, using whole exome sequencing, followed by linkage-by-location, a three base pair deletion in exon 33 of MYH7 (p.Glu1508del) was found, a reported pathogenic allele albeit for a myopathy. After identification of the causative molecular defect, cardiac examination was performed for patients of the third family and this demonstrated abnormalities in three out of five affected family members. Heterogeneity and expansion of clinical phenotypes beyond known characteristics requires a wider set of genes to be screened. Whole exome/genome analysis with limited prior clinical information may therefore be used to precede a detailed clinical evaluation in cases of large families, preventing screening of a too narrow set of genes, and enabling the identification of novel disease-associated genes. In our cases, the variants had been reported, and co-segregation analysis confirmed the molecular diagnosis.

[White matter abnormalities following attempted suicide]. / Wittestofafwijkingen na een zelfmoordpoging.

BACKGROUND: Delayed post-hypoxic leukoencephalopathy (DPHL) is a demyelinating disorder characterized by neuropsychiatric symptoms occurring a few days to some weeks following cerebral hypoxia. CASE DESCRIPTION: A 50-year old female patient showed rapidly progressive cognitive deterioration with apathy, mutism and regressive behaviour a few weeks after a suicide attempt with carbon monoxide (CO). This eventually leads to a state of akinetic mutism. Magnetic resonance imaging (MRI) of the brain showed diffuse white matter abnormalities. These MRI findings combined with CO intoxication and the clinical picture were highly suggestive for DPHL. CONCLUSION: This case emphasizes that a neurological cause should be considered if rapidly progressive neuropsychiatric symptoms occur, and that after suspected auto intoxication it is important to take possible hypoxia and its after-effects into consideration. Recognition of DPHL is important so that unnecessary invasive diagnostics and treatment can be avoided. Considering the favorable natural course of DPHL appropriate measures should be taken in order to provide supportive care and rehabilitation.