Case Report: Evidence of Tungiasis in the Amazon Rain Forest of Ecuador

Tungiasis occurs in tropical and subtropical areas in Central and South America and sub-Saharan Africa and is a Neglected Tropical Disease. We diagnosed three cases of tungiasis in a Dutch family visiting indigenous communities in the Amazon basin of Ecuador. Eight days after returning, they presented papular, pruritic, and painful lesions on the feet, with a whitish halo and a blackish central point with abundant whitish eggs upon extraction. For the first time, we demonstrate that Tunga spp. transmission is present in remote indigenous communities in the Amazon rainforest of Ecuador. It will be important to investigate the occurrence of tungiasis and associated morbidity among local inhabitants and consider prevention measures among locals and travelers to these areas.

Unusual cause of congenital hypothyroidism in a term infant

Both insufficient and excessive maternal iodine consumption can result in congenital hypothyroidism. In East Asian cultures, seaweed is traditionally consumed in high quantities by peripartum women as it is thought to improve lactation. We present a case of transient congenital hypothyroidism due to maternal seaweed consumption at a daily basis during pregnancy and lactation in a Dutch family without Asian background. This case highlights that even in families of non-Asian background, high maternal intake of iodine-rich seaweed occurs and can result in transient or permanent hyperthyrotropinemia in the neonate with risk of impaired neurodevelopmental outcome if untreated.

Effects of a Dutch Family Literacy Program: The Role of Implementation

It is hypothesized that variability found in the effects of family literacy programs results from differences in implementation by parents. In this study, the implementation and effects of a Dutch program were examined in a sample of 207 kindergarteners (mean age at pre-test: 64 months). No main intervention effects on children’s literacy development were found. The quality of implementation proved to be higher for high-SES and native Dutch (speaking) parents than for low-SES, ethnic-minority parents with other home languages. Parent SES, ethnic-minority status, and home language did not moderate the program effects on child language scores and the program failed to impact targeted parental attributes, namely, the home literacy environment and parent self-efficacy. Finally, children’s development proved unrelated to implementation variables. Our results stress the importance of delivery for adequate implementation.

Rare functional missense variants in CACNA1H: What can we learn from Writer’s cramp?

Writer’s cramp (WC) is a task-specific focal dystonia that occurs selectively in the hand and arm during writing. Previous studies have shown a role for genetics in the pathology of task-specific focal dystonia. However, to date, no causal gene has been reported for task-specific focal dystonia, including WC. In this study, we investigated the genetic background of a large Dutch family with autosomal dominant‒inherited WC that was negative for mutations in known dystonia genes. Whole exome sequencing identified 4 rare variants of unknown significance that segregated in the family. One candidate gene was selected for follow-up, Calcium Voltage-Gated Channel Subunit Alpha1 H, CACNA1H, due to its links with the known dystonia gene Potassium Channel Tetramerization Domain Containing 17, KCTD17, and with paroxysmal movement disorders. Targeted resequencing of CACNA1H in 82 WC cases identified another rare, putative damaging variant in a familial WC case that did not segregate. Using structural modelling and functional studies in vitro, we show that both the segregating p.Arg481Cys variant and the non-segregating p.Glu1881Lys variant very likely cause structural changes to the Cav3.2 protein and lead to similar gains of function, as seen in an accelerated recovery from inactivation. Both mutant channels are thus available for re-activation earlier, which may lead to an increase in intracellular calcium and increased neuronal excitability. Overall, we conclude that rare functional variants in CACNA1H need to be interpreted very carefully, and additional studies are needed to prove that the p.Arg481Cys variant is the cause of WC in the large Dutch family.

Exploring the Prescribing Process of Domperidone for Low Milk Supply: A Qualitative Study Among Mothers, IBCLCs, and Family Doctors

Background When mothers are confronted with milk supply problems, taking domperidone is regularly suggested. However, domperidone has been associated with sudden cardiac death and caution in prescribing is advised. In 2016, a multidisciplinary group of authors from a tertiary academic hospital (Erasmus MC) published a clinical protocol in a leading Dutch physicians’ journal to support Dutch family physicians in prescribing domperidone to stimulate lactation. Research aim To explore consumer and health care provider perspectives and experiences regarding the prescribing of domperidone for lactation insufficiency following publication of a national clinical protocol. Methods A cross-sectional qualitative study was performed using semi-structured interviews ( N = 40) based on a topic list covering the prescribing process. Participants were mothers ( n = 18) who had been advised to try domperidone to boost their milk supply between November 2016 and May 2018, their International Board Certified Lactation Consultants ( n = 9), and their family physicians ( n = 15). Another group of participants (mothers; n = 6) answered short questionnaires. All interviews were recorded, transcribed and analyzed using ATLAS.ti software. The resulting list of codes was organized according to the topics. Results In the process leading to domperidone use to stimulate lactation, participant family physicians relied on the IBCLC, pharmacist, or mother to guide the prescription of domperidone, often citing the published national clinical protocol as back up. The medical safeguards incorporated in the protocol (e.g., taking medical history, physical exam, performing electrocardiograms, limiting dosage) were usually not implemented. Conclusions Though the availability of a national clinical protocol in which the prescribing of domperidone for lactation is supported appeared to increase the willingness of participant family physicians to prescribe, gaps were identified between clinical practice and this clinical protocol for prescribing domperidone.

NEK11 as a candidate high-penetrance melanoma susceptibility gene

BackgroundA proportion of patients diagnosed with cutaneous melanoma reports a positive family history. Inherited variants in CDKN2A and several other genes have been shown to predispose to melanoma; however, the genetic basis of familial melanoma remains unknown in most cases. The objective of this study was to provide insight into the genetic basis of familial melanoma.MethodsIn order to identify novel melanoma susceptibility genes, whole exome sequencing (WES) analysis was applied in a Dutch family with melanoma. The causality of a candidate variant was characterised by performing cosegregation analysis in five affected family members using patient-derived tissues and digital droplet PCR analysis to accurately quantify mutant allele frequency. Functional in-vitro studies were performed to assess the pathogenicity of the candidate variant.ResultsApplication of WES identified a rare, nonsense variant in the NEK11 gene (c.1120C>T, p.Arg374Ter), cosegregating in all five affected members of a Dutch family. NEK11 (NIMA-related Kinase 11) is involved in the DNA damage response, enforcing the G2/M cell cycle checkpoint. In a melanoma from a variant carrier, somatic loss of the wildtype allele of this putative tumour suppressor gene was demonstrated. Functional analyses showed that the NEK11 p.Arg374Ter mutation results in strongly reduced expression of the truncated protein caused by proteasomal degradation.ConclusionThe NEK11 p.Arg374Ter variant identified in this family leads to loss-of-function through protein instability. Collectively, these findings support NEK11 as a melanoma susceptibility gene.