SOD1-related ALS with anticipation in a large family from Martinique.

Amyotrophic Lateral Sclerosis (ALS) is a rare neurological disorder that causes degeneration of upper and lower motor neurons and their axons. ALS is mostly sporadic, but there are familial forms. In more than half of the familial forms, a pathogenic variant is found in one of the following genes: C9ORF72, SOD1, TDP-43, FUS, and VCP. SOD1 is the 2nd most common gene involved in genetic forms of ALS. Genotype-phenotype relationships are occasionally established in genetic forms of ALS associated with SOD1 mutations pathogenic variants. The c.281G > T (p.[G93V]) variant in SOD1 is associated with a rarely described and unexplained anticipation phenomenon. We report a large family from Martinique in whom ALS is associated with a c.281G > T (p.[G93V]) pathogenic variant in SOD1 and a statistically suggested anticipation. A whole-exome study and detection of CNVs (CoDESeq) from 3 affected members of this family revealed the presence of variants of uncertain signification (VUS) in other ALS genes. VUS in DCTN1 and NEFH were present in patients of the 2nd generation, and CNVs involving UBQLN2 and C21orf2 were found in the youngest case of the family.

Retrospective clinic and urodynamic study in the neurogenic bladder dysfunction caused by human T cell lymphotrophic virus type 1 associated myelopathy/tropical spastic paraparesis (HAM/TSP).

INTRODUCTION: HTLV-I associated tropical spastic paraparesis (TSP) and HTLV-I associated myelopathy (HAM) is an endemic disease in Caribbean Island. Bladder-sphincter dysfunctions are almost present. The objectives of the study are to describe clinic and urodynamic characteristics of voiding disorders in Martiniquan population, evaluate if there is a relationship between motor and urinary handicap, and evaluate prognosis factors of urologic complications. METHODS: Retrospective study of 60 patients suffering from HAM/TSP. Clinical, urodynamic datas, scale of urinary and motor handicap (Urinary Symptom Profile [USP] questionnaire and Osame Score) were collected. RESULTS: Storage symptoms were the most frequent (75%) whatever type of detrusor activity. Detrusor overactivity was the most frequent disorder (68.3%). Bladder compliance was normal in half percent of the cases. Urethral activity was increased in 47% of the cases. Detrusor sphincter dysynergia was found in 78% of the cases, post-void residual in 58% of cases. Sixty five percent of the patients present at least one urologic complication (morphologic and/or infectious) but there was no correlation with motor enablement (P = 0.3097), neither urodynamic study (P = 0.432 for detrusor overactivity, P = 0.107 for detrusor underactivity, P = 0.058 for high urethral activity, P = 0.893 for detrusor sphincter dysynergia, P = 0.850 for post-void residual volume), neither with evolution duration of HAM/TSP (P = 0.348). USP score was not in correlation with Osame score (P = 0.07). CONCLUSION: Urologic symptoms are not always in relationship with urodynamic study: a systematic urodynamic study is necessary to evaluate HAM/TSP neurogenic bladder. No clinic or urodynamic criterias are predictive of urologic complications. These patients need a close follow up. Neurourol. Urodynam. 36:449-452, 2017. © 2016 Wiley Periodicals, Inc.