Particularités du cancer du larynx chez le sujet jeune / Epidemiological and clinical predictive factors of success in septoplasty: Study of 250 patients

Discuter à travers une étude descriptive ainsi qu'une revue de la littérature, les particularités cliniques, démographiques et pronostiques des patients de moins de 45 ans, ayant un cancer du larynx. Materiels et Methodes: Il s'agit d'une étude rétrospective descriptive portant sur des patients atteints d'un cancer du larynx, âgés de moins de 45 ans suivis dans le service d'ORL et de chirurgie cervico-faciale du CHU Habib Bourguiba Sfax durant la période s'étendant de 1989 à 2018. Resultats: Nous avons trouvé 31 patients avec une prédominance masculine. Un cancer dans la famille a été trouvé dans 16,12% des cas sans corrélation statistique avec le stade avancé de la maladie. Une importante intoxication tabagique a été trouvée (96%). Trois patients avaient une laryngite chronique et un patient une papillomatose laryngée avec des lésions de dysplasie. Les motifs de consultation étaient dominés par la dysphonie (87%). La maladie a été classée en stades avancés dans 70% des cas. Le traitement chirurgical était préconisé chez 87% des patients et la préservation fonctionnelle chez 38,7%. Le taux de survie globale et sans maladie étaient respectivement, à un an de 96% et 84%, à 3 ans de 87% et 76%, et à 5 ans de 77% et 75% Conclusion: Notre travail n'a pas permis de retenir de différence en termes de données cliniques, de l'évolution de la maladie, de l'algorithme thérapeutique ni du pronostic entre les jeunes patients et les plus âgés

SQSTM1 mutation: Description of the first Tunisian case and literature review.

BACKGROUND: Mutations in SQSTM1 gene have been recently identified as a rare cause of progressive childhood neurodegenerative disorder. So far, only 25 patients from 10 unrelated families were reported. METHODS AND RESULTS: We report on the first Tunisian case of an 11-year-old girl with cerebellar ataxia, chorea and ophthalmoparesis. Brain MRI was normal. Whole-exome sequencing revealed a homozygous mutation c.823_824del(p.Ser275Phefs*17) in SQSTM1 gene (GenBank: NM_003900.4). CONCLUSION: By pooling our data to the data of literature, we delineated the phenotypic spectrum and stressed on genetic heterogeneity of this rare neurodegenerative disease.

[Parathyromatosis: An uncommon cause of recurrent hyperparathyroidism]. / Parathyromatose : une cause rare d'hyperparathyroïdie récidivante.

INTRODUCTION: Parathyromatosis is a rare cause of recurrent hyperparathyroidism. It results from hyperfunctioning parathyroid tissue scattered throughout the thyroid bed region. CASE REPORT: A 51-year-old man with a history of parathyroidectomy, presented 18 years later with recurrent primary hyperparathyroidism. Surgical exploration identified a single parathyroid gland. The act was completed by a central compartment dissection and ipsilateral lobectomy. The patient was free of recurrence after a one-year follow-up. CONCLUSION: Parathyromatosis a rare cause of recurrent hyperparathyroidism. Its management is challenging. Extensive surgery is required with clearance of the central neck compartment and homolateral lobectomy. Medical therapy could be used to decrease parathormone level in recurrent parathyromatosis.

Burkitt lymphoma in a child with Bloom syndrome.

BACKGROUND: Bloom syndrome is a rare disease characterized by chromosomal instability and increased risk of developing lymphoma. OBSERVATION: We report on a case of Bloom syndrome in a 5-year-old boy with Burkitt lymphoma. The diagnosis was suspected by growth retardation, repeated respiratory infections, facial telangiectasia, and a low immunoglobulin level, then confirmed cytogenetically by sister chromatid exchanges. Chemotherapy was poorly tolerated, which required reducing the doses. Unfortunately, it was not sufficient to control the neoplasm and the patient died 14 months after diagnosis. CONCLUSIONS: Cancers in Bloom syndrome are a challenge since the potentially life-threatening side effects of the chemotherapy may require modifications in standard treatment such as dose reduction, which can compromise the tumor prognosis.

Clinical and genetic characterization of Bardet-Biedl syndrome in Tunisia: defining a strategy for molecular diagnosis.

Bardet-Biedl syndrome (BBS, OMIM 209900) is a rare genetic disorder characterized by obesity, retinitis pigmentosa, post axial polydactyly, cognitive impairment, renal anomalies and hypogonadism. The aim of this study is to provide a comprehensive clinical and molecular analysis of a cohort of 11 Tunisian BBS consanguineous families in order to give insight into clinical and genetic spectrum and the genotype-phenotype correlations. Molecular analysis using combined sequence capture and high-throughput sequencing of 30 ciliopathies genes revealed 11 mutations in 11 studied families. Five mutations were novel and six were previously described. Novel mutations included c.1110G>A and c.39delA (p.G13fs*41) in BBS1, c.115+5G>A in BBS2, c.1272+1G>A in BBS6, c.1181_1182insGCATTTATACC in BBS10 (p.S396Lfs*6). Described mutations included c.436C>T (p.R146*) and c.1473+4A>G in BBS1, c.565C> (p.R189*) in BBS2, deletion of exons 4-6 in BBS4, c.149T>G (p.L50R) in BBS5, and c.459+1G>A in BBS8; most frequent mutations were described in BBS1 (4/11, 37%) and BBS2 (2/11, 18%) genes. No phenotype-genotype correlation was evidenced. This data expands the mutations profile of BBS genes in Tunisia and suggests a divergence of the genetic spectrum comparing Tunisian and other populations.

[Rubella seroprevalence in Tunisian childbearing women two years after vaccination program introduction]. / Séroprévalence de la rubéole chez la femme en âge de procréer deux ans après l'introduction de la vaccination en Tunisie.

UNLABELLED: Acquiring rubella during the first 20 weeks of pregnancy can lead to teratogenic effects. AIM: The aim of the study was to investigate the impact of rubella vaccination strategy two years after its introduction in Tunisia in 2005. METHODS: This study was conducted over two periods, 2000 and 2007-2008. A total of 15,776 childbearing women were enrolled in the sample. Serological studies were performed by using the ELISA method. RESULTS: Overall, rubella infection seroprevalence did not increase between 2000 and 2007-2008. Nevertheless, a significant increase in seroprevalence, from 78.2% in 2000 to 92% in 2007-2008 (P=0.006), was especially noted in the age group under 20 years. Seroprevalence did also statistically increase with parity in 2007-2008 from 77.4% in women without any parity to 89.8% in women with over three parities (P=0.01). CONCLUSIONS: Results improvements seem most likely due to mass vaccination campaign for girls aged from 13 to 18 years in 2005, and also routinely post-partum vaccination of seronegative pregnant women or women ignoring their rubella status. In the coming years, systematic selective immunization of 12-year-old schoolgirls who are not yet entering their prime childbearing years will achieve female population sufficient immunity.

[Nonketotic hyperglycemia-induced hemiballism]. / Hémiballisme secondaire à une hyperglycémie sans cétose.

Nonketotic hyperglycemia-induced hemichorea or hemiballism is a well-recognized entity that is rarely encountered. Particular computed tomography and magnetic resonance imaging findings have been described. The pathophysiological mechanism of this disease remains uncertain. We report here on two female patients that presented with hemiballism secondary to nonketotic hyperglycemia and underwent brain computed tomography and magnetic resonance imaging.

Only two mutations detected in 15 Tunisian patients with 11ß-hydroxylase deficiency: the p.Q356X and the novel p.G379V.

Steroid 11ß-hydroxylase deficiency is the second most common cause of congenital adrenal hyperplasia, resulting in virilization, glucocorticoid deficiency and hypertension. The 11ß-hydroxylase enzyme is encoded by the CYP11B1 gene and mutations in this gene are responsible for this disease. The aim of this study was to characterize mutations in the CYP11B1 gene and to determine their frequencies in a cohort of Tunisian patients. The molecular genetic analysis was performed by direct nucleotide sequencing of the CYP11B1 gene in 15 unrelated Tunisian patients suffering from classical 11ß-hydroxylase deficiency. Only two mutations were detected in homozygous state in the CYP11B1 gene of all patients, the p.Q356X in exon 6 (26.6%) and the novel p.G379V in exon 7 with large prevalence (73.3%). This is the first report of screening for mutations of CYP11B1 gene in the Tunisian population and even in the Arab population.

A novel UBE3A truncating mutation in large Tunisian Angelman syndrome pedigree.

We identified in a large Tunisian pedigree a novel UBE3A frameshift mutation in exon 16 coding region, and we expect that the resulting UBE3A truncated protein in our patients is non-functional since the mutation implies the catalytic region of the enzyme. The family includes 14 affected patients born from four sisters. This mutation was found in all surviving affected individuals and their mothers pointing out the importance of genetic counseling possibility in Angelman syndrome (AS). All patients had severe mental retardation with epilepsy and microcephaly. Minor clinical expression variation was observed among the investigated patients. The severity of clinical expression is related to the detected molecular variation: deletion of 15 bp and insertion of 7 bp. These results are concordant with the gene expression observed in previously reported individuals with AS and truncated UBE3A protein.

Comparison of hepatitis A seroprevalence in blood donors in South Tunisia between 2000 and 2007.

The aim of the study was to assess hepatitis A virus (HAV) seroprevalence in blood donors from South Tunisia in two periods 2000 and 2007. Serum samples collected from 376 blood donors in each period aged 18 to 30 years from different regions of South Tunisia were analysed for anti-HAV IgG. The global seroprevalence of HAV infection was 85.9% in 2007 as compared with 94.9% in 2000. The seroprevalence in the 18-20 years age group was 91.9% in 2000 vs 80.6% in 2007, and increased to 99% in 2000 and 92% in 2007 in the subjects over 26. Taking account of geographic area, the HAV seroprevalence in Sfax city decreased from 88.9% in 2000 to 62.7% in 2007 (p < 0.001), but it is still approximatively the same in rural areas (98.4% and 96%) and in the governorates of South Tunisia (97.6% and 99.2%). In conclusion, the number of adults in the city of Sfax which are not immunized against HAV is increasing. Thus, adolescents and young adults are at risk to develop symptomatic and potentially severe hepatitis A.

[Genetic analysis of Turner syndrome: 89 cases in Tunisia]. / Analyse génétique du syndrome de Turner : étude tunisienne de 89 cas.

Turner's syndrome (TS) affects about 1/2500 female infants born alive. The syndrome results from total or partial absence of one of the two X chromosomes normally present in females. We report the results of a retrospective analysis of 89 cases of TS observed during a six-year period (2000-2005). The patients' age ranged from two days to 51 years at the time of this analysis. Most patients were adults (48%). The aim of this study is to ascertain the principal clinical features leading to a request for a karyotype, searching for a possible relationship between chromosomal anomalies and clinical expression of TS. Pediatric patients were referred for statural retardation or dysmorphic features, while reproduction anomalies were the main indication for karyotyping in patients aged over 20 years. Mosaicism was prevalent (47%), whereas the homogeneous karyotype 45,X was found in only 32% of the patients; structural anomalies were found in 21%. Regarding the advanced age of our patients, we established a relationship between chromosome anomalies and the clinical expression of TS, based on an analysis of stature and reproduction disorders. Short stature and primary amenorrhea were correlated with total deletion of one chromosome X or imbalanced gene dosage due to structural X anomalies. Whereas cases of infertility, recurrent miscarriages and secondary amenorrhea were associated with a mosaic karyotype pattern (45,X/46,XX or 45,X/46,XX/47,XXX ...), with a slight mosaicism in most cases. Thus, chromosome investigations should be performed in cases of reproduction failure even for women with normal stature.

[Retinal neovascularization with myelinated nerve fibers]. / Néovaisseaux rétiniens compliquant des fibres à myéline.

INTRODUCTION: The prevalence of myelinated retinal nerve fibers is 0.3%-0.6% of eyes. Although they often constitute benign lesions, they are rarely associated with retinal vascular abnormalities including preretinal neovascularization. CASE REPORT: A 31-year-old patient, with no previous pathological antecedents, consulted us for myodesopsia in her left eye. The exam found a visual acuity of 10/10 and a normal anterior segment in the two eyes. At the ophthalmoscopic examination of the left eye, we noted myelinated nerve fibers in the inferotemporal quadrant that were associated with a temporal neovascular bouquet covering area of 1.5 optic disks. A small amount of intravitreal hemorrhage was found. The ophthalmoscopic examination of the right eye was normal. The treatment consisted in sector-based photocoagulation with argon laser and cryotherapy. DISCUSSION: The source of neovascularization in the myelinated retinal nerve fibers was discussed. Underlying retinal ischemia is the most probable mechanism. The treatment was based on sector-based or panretinal photocoagulation. CONCLUSION: Preretinal neovascularization is a rare complication of myelinated nerve fibers. The earlier the care is given, the more complications can be avoided.

Y chromosome microdeletions in Tunisian infertile males.

AIM: To determine frequency of Y microdeletions in azoospermic and oligospermic Tunisian infertile males. METHODS: A Sample of 146 Tunisian infertile males with a low sperm count (<5 x 10(6) sperms per mililiter) and normal karyotype was screened for Y chromosome microdeletions. 76 men were azoospermic and 70 men were oligospermic. Genomic DNA was isolated from blood and multiplex PCR was carried out with a set of 20 AZFa, AZFb and AZFc STS markers to detect the microdeletions as recommended by the European Academy of Andrology. RESULTS: In 10/146 (6.85%) subjects AZF deletions were observed. Of these ten males with microdeletions, 9/10 subjects were azoospermic (90%), 1/10 was oligospermic (10%). Frequency of microdeletions in azoospermic men was 9/76 (11.84%). None of the patients showed isolated microdeletion in the AZFa region, but one azoospermic man had deletion in the AZFb region. Eight azoospermic patients and one oligospremic man have AZFc microdeletions. AZFc and AZFb were deleted in three azoospermic patients. AZFc, AZFb and AZFa were deleted in three azoospermic patients We estimate the sensitivity of the test comprising six STS in our sample to be 90%. CONCLUSION: The incidence of Yq microdeletions in the study population of infertile Tunisian men falls within the range published in other countries. We suggest to analyze 9STS in the first step to detect efficiently Y microdeletions in our population.

[Devic's neuromyelitis optica in children: a case report and review of the literature]. / Neuromyélite optique de Devic chez l'enfant: à propos de 1 cas, avec revue de la littérature.

UNLABELLED: Devic neuromyelitis optica (NMO) or Devic's syndrome is an uncommon clinical syndrome associating unilateral or bilateral optic neuritis and transverse myelitis. Usually reported in adults, childhood cases constitute a distinctive clinical entity. CASE REPORT: We report a case of NMO occurring in a 9-year-old girl, admitted for paraplegia, sphincter troubles as acute installation bladder retention and of a sudden decline of the visual acuity. Magnetic resonance imaging (MRI) revealed abnormalities of spinal cord signal with hypo intensity in T1-weighted images and hyper intensity in T2-weighted images along the spinal cord. However, the cerebral region was normal. Visual evoked potentials were consistent with retrobulbar optic neuropathy. Our patient received corticosteroids (methyl prednisolone) during 5 days followed by oral prednisone. At week three, an immunosuppressant (azathioprine) was added. Clinical outcome was favourable with disappearance of sphincter troubles, a correction of the visual acuity and a progressive disappearance of motor troubles. CONCLUSION: Pediatric Devic's NMO is rare. It is a different clinical entity with an excellent visual and neurological prognosis. Review of the literature shows that recurrence is rare in children and seems to be without long-term sequelae with corticosteroids and immunosuppressant therapy.

[Mucopolysaccharidosis type I: identification of alpha-L-iduronidase mutations in Tunisian families]. / La mucopolysaccharidose de type I: identification des mutations du gène alpha-L-iduronidase dans des familles tunisiennes.

UNLABELLED: Mucopolysaccharidosis type I (MPS I) is a lysosomal disease due to mutations in the gene encoding alpha-l-iduronidase (IDUA) leading to variable clinical phenotypes with progressive severe organomegaly, bone and neurological involvement in the most severe forms. The aim of our study was to propose in Tunisia a strategy of molecular and prenatal diagnosis of the MPS I. POPULATION AND METHODS: Our study was carried out on 8 MPS I patients recruited from different Tunisian regions and issued from 5 unrelated families. All the patients were offspring of consanguineous marriages. RESULTS: The clinical and biological study led to diagnose 5 Hurler patients and 3 Hurler-Scheie patients. Three IDUA mutations were identified by molecular analysis within 6 different families: a novel mutation p.F602X and 2 already described mutations p.P533R and p.R628X. DISCUSSION: MPS I is a heterogeneous disease characterized by variability of the phenotypes. The missense mutation p.P533R associated with the intermediate phenotype was the most frequent in the Tunisian but also in the Moroccan population. In Tunisia, the incidence of p.P533R mutation seems to be associated with the high frequency of consanguineous marriages. CONCLUSION: The identification of known MPS I mutations (p.P533R and p.R628X) and of the novel mutation p.F602X permits reliable genetic counselling of at-risk relatives and molecular prenatal diagnosis.

[Diagnostic strategy of mucopolysaccharidosis type I in Tunisia]. / La mucopolysaccharidose de type I: stratégie diagnostique en Tunisie.

A Tunisian patient affected by mucopolysaccharidosis (MPS) was investigated for a biological analysis (quantitative and qualitative glycosaminoglycans (GAG) screening). We have also done an enzymatic determination of alpha-L-iduronidase activity (IDUA). The most common mutation (p.Gln 70 X, p.Trp 402X and p.Pro 533 Arg) were researched by an enzymatic restriction and sequencing of the IDUA gene. Enzymatic and urinary diagnostics suggested a MPS I phenotype. The patient investigated had the mutation p.Pro 533 Arg in the homozygous status, whereas his parents were heterozygous for this mutation.

[Clinical, biologic and molecular characteristics of two Tunisian MPS IV A patients]. / Etude de la maladie de Morquio A dans une famille tunisienne présentant deux enfants atteints.

Mucopolysaccharidosis type IV A (MPS IV A) is an autosomal recessive disorder resulting from the deficient activity of the lysosomal enzyme, N-acetylgalactosamine-6-sulfate sulfatase (GALNS) and the progressive lysosomal accumulation of keratane sulfate. Clinically, the MPS IV A differs from the other MPS by the localisation of the keratane sulfate in skelet and in eyes associated to the conservation of a normal intelligence. To date, the characterization and purification of the GALNS gene made a research for pathogenic mutations in patients with MPS IV A easier. These mutations are responsible of severe, intermediate or mild phenotype. The aim for this work was the research of clinical, biologic and molecular characteristics of two Tunisian MPS IV A patients who were offsprings of consanguineous mating. Enzymatic and urinary diagnostics suggested a MPS IV A phenotype. A novel homozygous mutation IVS1+1G-A was identified by direct sequencing in the GALNS gene of the two patients. Identification of GALNS mutations provide genotype/phenotype correlations and permit the precision of anomalies responsible of Morquio A phenotype in concerned families.