Cataract as a phenotypic marker for a mutation in WFS1, the Wolfram syndrome gene

PURPOSE: Wolfram syndrome (WS) or diabetes insipidus, diabetes mellitus, optic atrophy, and deafness (DIDMOAD) (OMIM 222300) is an inherited neurodegenerative disease characterized by diabetes mellitus and optic atrophy as the 2 major criteria, followed later in life by deafness, diabetes insipidus, and various signs of neurologic impairment. The presence of a cataract has been variably mentioned in WS. METHOD: Two members of a family had thorough ophthalmic examination and their DNA was screened for mutations in mitochondrial DNA, WFS1, OPA1, and OPA3 genes. RESULTS: We report a patient who first had surgery for bilateral cataract at age 5 and who subsequently presented typical signs of WS, i.e., diabetes mellitus, optic atrophy with reduced visual acuity at 20/400 on both eyes at age 22, and mild deafness. The patient was found to be a compound heterozygote for 2 truncating mutations in WFS1, the major WS gene. She carried the previously reported c.1231_1233 delCT and a novel c.2431_2465dup35 mutation. She also was heterozygote for a novel OPA1 sequence variant, c.929A>G in exon 9, whose pathogenicity remains uncertain. The patient\u27s mother was a heterozygous carrier of the c.2431_2465dup35 mutation. She did not have diabetes mellitus or optic atrophy but had bilateral polar cataract. She did not carry the OPA1 sequence variant. CONCLUSIONS: Cataract could be a marker for the WFS1 heterozygosity in this family, namely the c.2431_2465dup35 mutation

Partial acute transverse myelitis is a predictor of multiple sclerosis in children

International audienceBackground: Acute transverse myelitis (ATM) in children is a rare and often severe disease for which there are few known prognostic factors, particularly the subsequent risk of multiple sclerosis (MS) diagnosis.Objectives: To determine the clinical course and prognostic factors after a first episode of ATM in children.Methods: Thirty children below 16 years of age diagnosed with a first neurological episode of ATM were included retrospectively. Clinical evaluation, treatment, laboratory, and MRI data were collected.Results: Median age at onset was 11 years (range 3-15 years). Follow-up data were available for a median of 4 years (range 0.5-16.7 years). Five patients subsequently had a diagnosis of MS (17%), which was associated with acute partial transverse myelitis (odds ratio 5; 95% confidence interval 2.3-11), with a 60% probability of having a relapse at five years (p < 0.01). The 2011 Verhey criteria correctly identified MS in children with the highest specificity (96%) and sensitivity (80%).Conclusion: Acute partial transverse myelitis and brain MRI abnormalities at initial presentation are significantly predictive of a subsequent diagnosis of MS in children with ATM. These findings suggest that closer brain MRI monitoring after acute partial transverse myelitis might make the earlier introduction of disease-modifying therapies possible

Effects of seizures, kindling, and carbamazepine on sleep organization in cats

We studied the relationships between epilepsy, sleep, and anticonvulsant drugs in kindled cats. No sleep alteration was present at midkindling. When the animals became fully kindled, a reduction in REM sleep percentage and the number of entries into REM sleep were observed compared to baseline. In addition, with further seizures, an increase in the percentage of wakefulness appeared, accompanied by a further reduction in the number of entries into REM sleep. It therefore seems that there is a progressive disruption of sleep, dependent on the increasing number of tonic-clonic generalized seizures. After a seizure-free interval, REM sleep and wakefulness returned to baseline values. A reduction in the percentage of stage II compared to baseline was found and remained as a long-term effect of the kindling process. Acute administration of carbamazepine (CBZ) reduced the REM sleep percentage. This effect, paralleled by a reduction in the number of entries into REM sleep, was evident both at baseline and when the animals were fully kindled. After a large number of seizures, however, CBZ administration did not cause a further reduction in the already low percentage of REM sleep. Results are discussed with reference to previous literature. We propose a hypothesis of competition between seizure and REM sleep in the elimination of epileptogenic and hypnogenic factors