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PLPHP (pyridoxal-phosphate homeostasis protein) deficiency is caused by biallelic pathogenic variants in PLPBP and is a rare cause of pyridoxine-responsive disorders. We describe three French-Canadian individuals with PLPHP deficiency, including one with unusual paroxysmal episodes lacking EEG correlation with a suspicious movement disorder, rarely reported in B6RDs. In addition, we review the clinical features and treatment responses of all 51 previously published individuals with PLPHP deficiency. Our case series underlines the importance of considering PLPBP mutations in individuals with partially B6-responsive seizures and highlights the presence of a founder effect in the French-Canadian population.

Abstract Pyridoxine‐dependent epilepsy (PDE) is a relatively rare subgroup of epileptic disorders. They generally present in infancy as an early onset epileptic encephalopathy or seizures, refractory to standard treatments, with rapid and variable responses to vitamin B6 treatment. Whole exome sequencing of three unrelated families identified homozygous pathogenic mutation c.370_373del, p.Asp124fs in PLPBP gene in five persons. Haplotype analysis showed a single shared profile for the affected persons and their parents, leading to a hypothesis about founder effect of the mutation in Saguenay‐Lac‐St‐Jean region of French Canadians. All affected probands also shared one single mitochondrial haplotype T2b3 and two rare variations in the mitochondrial genome m.801A>G and m.5166A>G suggesting that a single individual female introduced PLPBP mutation c.370_373del, p.Asp124fs in Quebec. The mutation p.Asp124fs causes a severe disease phenotype with delayed myelination and cortical/subcortical brain atrophy. The most noteworthy radiological finding in this Quebec founder mutation is the presence of the temporal cysts that can be used as a marker of the disease. Also, both patients, who are alive, had a history of prenatal supplements taken by their mothers as antiemetic medication with high doses of pyridoxine. In the context of suspected PDE in patients with neonatal refractory seizures, treatment with pyridoxine and/or Pyridoxal‐5‐phophate has to be started immediately and continued until the results of genetic analysis received. Even with early appropriate treatment, neurological outcome of our patient is still poor.

Abstract Background Primary microcephaly is defined as reduced occipital-frontal circumference noticeable before 36 weeks of gestation. Large amount of insults might lead to microcephaly including infections, hypoxia and genetic mutations. More than 16 genes are described in autosomal recessive primary microcephaly. However, the cause of microcephaly remains unclear in many cases after extensive investigations and genetic screening. Case presentation Here, we described the case of a boy with primary microcephaly who presented to a neurology clinic with short stature, global development delay, dyskinetic movement, strabismus and dysmorphic features. We performed microcephaly investigations and genetic panels. Then, we performed whole-exome sequencing to identify any genetic cause. Microcephaly investigations and genetic panels were negative, but we found a new D317V homozygous mutation in TELOE-2 interacting protein 2 (TTI2) gene by whole-exome sequencing. TTI2 is implicated in DNA damage response and mutation in that gene was previously described in mental retardation, autosomal recessive 39. Conclusions We described the first French Canadian case with primary microcephaly and global developmental delay secondary to a new D317V homozygous mutation in TTI2 gene. Our report also highlights the importance of TTI2 protein in brain development.

There are recent reports of associations of variants in the HPDL gene with a hereditary neurological disease that presents with a wide spectrum of clinical severity, ranging from severe neonatal encephalopathy with no psychomotor development to adolescent-onset uncomplicated spastic paraplegia. Here, we report two probands from unrelated families presenting with severe and intermediate variations of the clinical course. A homozygous variant in the HPDL gene was detected in each proband; however, there was no known parental consanguinity. We also highlight reductions in citrate synthase and mitochondrial complex I activity detected in both probands in different tissues, reflecting the previously proposed mitochondrial nature of disease pathogenesis associated with HPDL mutations. Further, we speculate on the functional consequences of the detected variants, although the function and substrate of the HPDL enzyme are currently unknown.

Nemaline myopathy is a rare disorder affecting the muscle sarcomere. Mutations in nebulin gene (NEB) are known to be responsible for about 50% of nemaline myopathy cases. Nebulin is a giant protein which is formed integrally with the sarcomeric thin filament. This complex gene is under extensive alternative splicing giving rise to multiple isoforms. In this study, we report a 6-year-old boy presenting with general muscular weaknesses. Identification of rod-shaped structures in the patient' biopsy raised doubt about the presence of a nemaline myopathy. Next-generation sequencing was used to identify a causative mutation for the patient syndrome. A homozygous deep intronic substitution was found in the intron 144 of the NEB. The variant was predicted by in silico tools to create a new donor splice site. Molecular analysis has shown that the mutation could alter splicing events of the nebulin gene leading to a significant decrease of isoforms level. This change in the expression level of nebulin could give rise to functional consequences in the sarcomere. These results are consistent with the phenotypes observed in the patient. Such a discovery of variants in this gene will allow a better understanding of the involvement of nebulin in neuromuscular diseases and help find new treatments for the nemaline myopathy.

Abstract Background Pleuropulmonary blastoma (PPB) is a rare childhood dysontogenetic intrathoracic neoplasm associated with an unfavourable clinical behaviour. Cases presentation We report pathological and cytogenetic findings in two cases of PPB at initial diagnosis and recurrence. Both tumors were classified as type III pneumoblastoma and histological findings were similar at diagnosis and relapse. In both cases, conventional cytogenetic techniques revealed complex numerical and structural chromosomal abnormalities. Molecular cytogenetic analysis (interphase/metaphase FISH and multicolor FISH) identified accurately chromosomal aberrations. In one case, TP53 gene deletion was detected on metaphase FISH. To date, only few cytogenetic data have been published about PPB. Conclusion The PPB genetic profile remains to be established and compared to others embryonal neoplasia. Our cytogenetic data are discussed reviewing cytogenetics PPBs published cases, illustrating the contribution of multicolor FISH in order to identify pathogenetically important recurrent aberrations in PPB.

Insomnia, the inability to sleep and feel refreshed the next morning is a common problem reported as the most prevalent sleep disorder worldwide. Recently, special interest has focused on the use of herbal anxiolytics such as valerian root. In the Arab world, and particularly Jordan where it is prescribed by pharmacists, valerian root may be considered a relatively new non-prescription sleep aid. The objective of the current study was to assess pharmacists’ perception and knowledge of valerian pharmacology, explore their dispensing practice of sedatives/hypnotics and to investigate the Jordanian customers’ behaviour and preferences towards sedative/hypnotics. Data from 568 community pharmacists surveyed in Jordan was analysed. Almost one-third of the pharmacists admitted that they were unaware of the anxiolytic mechanism of valerian and half of them described valerian as a “hypnotic” instead of an “anxiolytic”. None knew that it could be hazardous to co-administer valerian with benzodiazepines. Additionally, diphenhydramine was preferred in general over valerian as a sleep aid. It was also found that pharmacists and customers thought valerian to be less effective than pharmaceutical medication in the treatment of insomnia. Our findings reflect a poor knowledge among pharmacists and the community about valerian. The authors suggest it would be beneficial to instigate measures to increase the awareness of herbal products amongst pharmacists. [ABSTRACT FROM AUTHOR]

Summary: Introduction: The role of fine-needle aspiration cytology (FNAC) in the management of parotid tumours is still the subject of controversy. The purpose of this study was to determine the diagnostic value of FNAC in our institution in order to define its place in the diagnostic strategy. Patients and methods: This retrospective study was based on 249 patients who had undergone preoperative FNAC before being operated in our institution between 2001 and 2008. All examinations were performed and interpreted by the same experienced pathologist. Results: Among the 249 patients included in this study, 187 (75%) had a benign tumour and 62 (25%) had a malignant tumour. No complications of FNAC were observed. Cytological findings were non-contributory in 47 patients (18%). The sensitivity of FNAC for the diagnosis of malignancy was 80% with a specificity of 89.5%. Among the 11 false-negative results, lymphomas and low-grade mucoepidermoid carcinomas were the most common histological types. Among the 16 false-positive results, Warthin''s tumours, pleomorphic adenomas and lymphoepithelial lesions were the most common histological types. Accurate histological classification of the tumour was reported in 79.5% of cases (86% for benign tumours and 44% for malignant tumours). Conclusion: FNAC is a reliable examination providing important information to the surgeon in the preoperative diagnostic assessment. [Copyright &y& Elsevier]

The complex regional pain syndrome type 1 from the surgeon's point of view: description of the symptoms, imaging (nuclear medicine, MRI) and of the associated psychological context. Importance of the need for a multi-disciplinary organization from the diagnostic to the therapeutic care., (Copyright © 2011 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.)

Purpose of the Study: We present the cases of six adolescents (four high-level gymnastics specialists) with osteochondritis dissecans of the capitulum who were treated with an en bloc osteochondral autograft. There are few series of this rare condition reported in the literature., Material and Methods: All six patients presented pain over the lateral aspect of the elbow and limited extension; pronosupination was unaffected. Physical examination and plain X-rays enabled the diagnosis of osteochondritis dissecans. Postoperative X-rays confirmed good integration of the bone graft. These patients underwent lateral arthrotomy for curettage and avivement followed by an en bloc grafting. The graft was harvested from the homolateral knee via minimal arthrotomy, from a non-weight-bearing zone of the lateral condyle., Results: At three months, complete pain-free range of motion was achieved in four of six patients. Graft integration was confirmed in all six patients on the three months plain X-rays, arthro-CT, or MRI. The four gymnastic specialists resumed their high-level sports activities at one year (at six months for one of them)., Discussion: Various surgical methods have been proposed. Series reported in the literature, like ours, have been small, with short follow-up. We have observed good results with an en bloc graft, encouraging us to continue with this surgical strategy.

On the basis of 12 cases, the authors suggest use of the axillary approach in everyday surgery on the shoulder and the upper end of the humerus, because of the quality of healing it offers. They describe its safety and limitations. Problems are restricted to slight transverse adhesions across the axilla which are easily cured and even more easily avoidable.