Sodium dependent multivitamin transporter (SMVT) deficiency is a very rare autosomal recessive disorder characterized by multisystemic clinical manifestations due to combined biotin, panthotenic acid ...and lipoic acid deficiency. About 10 families have been described so far. Accurate diagnosis is crucial because of the possibility of a supplementation treatment with proven efficacy. Here we describe 4 new patients (3 additional families) originating from the same world region (Algeria, Maghreb). All patients, born form consanguineous parents, were homozygous carriers of the same intronic variation, outside of canonical sites, in the
SLC5A6
gene encoding SMVT. RNA study in one family allowed confirming the pathogenic effect of the variation and re-classifying this variant of uncertain significance as pathogenic, opening the possibility of genetic counseling and treatment. The identification of the same variation in three distinct and apparently unrelated families is suggestive of a founder effect. The phenotype of all patients was very similar, with systematic optic atrophy (initially considered as a very rare sign), severe cyclic vomiting, and rapidly progressive mixed axonal and demyelinating sensory motor neuropathy.
Sodium dependent multivitamin transporter (SMVT) deficiency is a very rare autosomal recessive disorder characterized by multisystemic clinical manifestations due to combined biotin, panthotenic acid ...and lipoic acid deficiency. About 10 families have been described so far. Accurate diagnosis is crucial because of the possibility of a supplementation treatment with proven efficacy. Here we describe 4 new patients (3 additional families) originating from the same world region (Algeria, Maghreb). All patients, born form consanguineous parents, were homozygous carriers of the same intronic variation, outside of canonical sites, in the
gene encoding SMVT. RNA study in one family allowed confirming the pathogenic effect of the variation and re-classifying this variant of uncertain significance as pathogenic, opening the possibility of genetic counseling and treatment. The identification of the same variation in three distinct and apparently unrelated families is suggestive of a founder effect. The phenotype of all patients was very similar, with systematic optic atrophy (initially considered as a very rare sign), severe cyclic vomiting, and rapidly progressive mixed axonal and demyelinating sensory motor neuropathy.
In this study, we describe the phenotype and genotype of the largest cohort of patients with Joubert syndrome (JS) carrying pathogenic variants on one of the most frequent causative genes,
.
We ...selected 53 patients with pathogenic variants on
, compiled and analysed their clinical, neuroimaging and genetic information and compared it to previous literature.
Developmental delay (motor and language) was nearly constant but patients had normal intellectual efficiency in 74% of cases (20/27 patients) and 68% followed mainstream schooling despite learning difficulties. Epilepsy was found in only 13% of cases. Only three patients had kidney cysts, only three had genuine retinal dystrophy and no subject had liver fibrosis or polydactyly. Brain MRIs showed typical signs of JS with rare additional features. Genotype-phenotype correlation findings demonstrate a homozygous truncating variant p.Arg950* linked to a more severe phenotype.
This study contradicts previous literature stating an association between
-related JS and ventriculomegaly. Our study implies that
-related JS is linked to positive neurodevelopmental outcome and low rate of other organ defects except for homozygous pathogenic variant p.Arg950*. This information will help modulate patient follow-up and provide families with accurate genetic counselling.
Objective
To describe the MR features enabling prenatal diagnosis of pontocerebellar hypoplasia (PCH).
Method
This was a retrospective single monocentre study. The inclusion criteria were decreased ...cerebellar biometry on dedicated neurosonography and available fetal Magnetic Resonance Imaging (MRI) with PCH diagnosis later confirmed either genetically or clinically on post‐natal MRI or by autopsy. The exclusion criteria were non‐available MRI and sonographic features suggestive of a known genetic or other pathologic diagnosis. The collected data were biometric or morphological imaging parameters, clinical outcome, termination of pregnancy (TOP), pathological findings and genetic analysis (karyotyping, chromosomal microarray, DNA sequencing targeted or exome). PCH was classified as classic, non‐classic, chromosomal, or unknown type.
Results
Forty‐two fetuses were diagnosed with PCH, of which 27 were referred for decreased transverse cerebellar diameter at screening ultrasound. Neurosonography and fetal MRI were performed at a mean gestational age of 29 + 4 and 31 + 0 weeks, respectively. Termination of pregnancy occurred. Pregnancy was terminated in 24 cases. Neuropathological examination confirmed the diagnosis in 24 cases and genetic testing identified abnormalities in 29 cases (28 families, 14 chromosomal anomaly). Classic PCH is associated with pontine atrophy and small MR measurements decreasing with advancing gestation.
Conclusion
This is the first large series of prenatally diagnosed PCHs. Our study shows the essential contribution of fetal MRI to the prenatal diagnosis of PCH. Classic PCHs are particularly severe and are associated with certain MR features.
Key points
What is already known about this topic?
Pontocerebellar hypoplasia (PCH) is a very rare disorder usually diagnosed after birth.
PCH is associated with severe psychomotor delay or even early death in childhood.
The onset of PCH is most often prenatal; however, prenatal identification is challenging with only single cases or very short case series being reported in the literature.
What does this study add?
We present the first large case series of 42 patients with prenatally diagnosed PCH.
MRI can accurately diagnose PCH with some imaging features predicting classic PCH.
On prenatal MRI, cerebellar area measurements correlate with psychomotor development.
Introduction
Microsurgical training is an asset for deployed military orthopaedic surgeons who frequently treat hand or nerve injuries in the field. The objective of this study was to evaluate a ...microvascular surgery simulation model intended to prepare residents prior to their enrolment in conventional microsurgery degree training.
Methods
An experimental study was conducted to evaluate technical progress and satisfaction of military surgical residents using a model based on Japanese noodles with four tests of increasing difficulty. Objective endpoints included instruments handling, distribution, and quality of stitches, as well as anastomoses duration. Responses to the Structured Assessment of Microsurgery Skill self-assessment questionnaire were also analyzed.
Results
Nine residents from different specialties participated in the study. Their anastomoses quality and average satisfaction significantly increased between the first and the last session (
p
< 0.05). Conversely, the average operating time decreased significantly over the sessions (
p
< 0.001).
Conclusion
This simulation model seems to constitute a satisfactory initiation to microsurgery and could limit the use of animal models. It could also be included in the continuing education of military surgeons who have an occasional microsurgical practice during deployments.
