AChR deficiency due to ε-subunit mutations: Two common mutations in the Netherlands

Congenital myasthenic syndromes are a clinically and genetically heterogeneous group of hereditary disorders affecting neuromuscular transmission. We have identified mutations within the acetylcholine receptor (AChR) ε-subunit gene underlying congenital myasthenic syndromes in nine patients (seven kinships) of Dutch origin. Previously reported mutations ε1369delG and εR311Q were found to be common; ε1369delG was present on at least one allele in seven of the nine patients, and εR311Q in six. Phenotypes ranged from relatively mild ptosis and external ophthalmoplegia to generalized myasthenia. The common occurrence of εR311Q and ε1369delG suggests a possible founder for each of these mutations originating in North Western Europe, possibly in Holland. Knowledge of the ethnic or geographic origin within Europe of AChR deficiency patients can help in targeting genetic screening and it may be possible to provide a rapid genetic diagnosis for patients of Dutch origin by screening first for εR311Q and ε1369delG

Incidence and outcome of acquired demyelinating syndromes in Dutch children: update of a nationwide and prospective study

Introduction: Acquired demyelinating syndromes (ADS) are immune-mediated demyelinating disorders of the central nervous system in children. A nationwide, multicentre and prospective cohort study was initiated in the Netherlands in 2006, with a reported ADS incidence of 0.66/100,000 per year and MS incidence of 0.15/100,000 per year in the period between 2007 and 2010. In this study, we provide an update on the incidence and the long-term follow-up of ADS in the Netherlands. Methods: Children < 18 years with a first attack of demyelination were included consecutively from January 2006 to December 2016. Diagnoses were based on the International Paediatric MS study group consensus criteria. Outcome data were collected by neurological and neuropsychological assessments, and telephone call assessments. Results: Between 2011 and 2016, 55/165 of the ADS patients were diagnosed with MS (33%). This resulted in an increased ADS and MS incidence of 0.80/100,000 per year and 0.26/100,000 per year, respectively. Since 2006 a total of 243 ADS patients have been included. During follow-up (median 55 months, IQR 28–84), 137 patients were diagnosed with monophasic disease (56%), 89 with MS (37%) and 17 with multiphasic disease other than MS (7%). At least one form of residual deficit including cognitive impairment was observed in 69% of all ADS patients, even in monophasic ADS. An Expanded Disability Status Scale score of ≥ 5.5 was reached in 3/89 MS patients (3%). Conclusion: The reported incidence of ADS in Dutch children has increased since 2010. Residual deficits are common in this group, even in monophasic patients. Therefore, long-term follow-up in ADS patients is warranted

Positional plagiocephaly and excessive folic acid intake during pregnancy

Objective: To assess the relationship between high intake of folic acid and positional plagiocephaly. Design: Retrospective case-control study with questionnaires administered in the clinic to biological mothers of children with positional plagiocephaly (PP group) and mothers of children without it (CO group). Setting: Tertiary, institutional clinic. University Hospital of Maastricht, The Netherlands. Patients, Participants: Exclusion criteria: mothers of children with syndromic disease or bone deformation and of children with clearly continuous forces on the skull (torticollis). A total of 94 mothers were included in the PP group (response rate: 85%), and 74 were included in the CO group (response rate: 75%). Final sample sizes were 75 in the PP group and 54 in the CO group. Main Outcome Measures: The recommended daily dosage of folic acid in The Netherlands is 400 mg. The primary outcome was folic acid dosage in relation to the recommended dosage. A secondary outcome was duration of folic acid intake in relation to the recommended period of use during pregnancy. Results: In the PP group, 20% used double the recommended dosage of folic acid, compared with 6% in the CO group (p < .05). In the CO group, 59% used folic acid longer than recommended compared with 56% in the PP group (not significant). There were no differences in baseline characteristics except for gestational period: 39.5 weeks in the PP group and 37.9 in the CO group (p<.05). Conclusion: Excessive daily intake of folic acid during pregnancy is seen among mothers of positional plagiocephaly patients