Occurrence of Hypopituitarism in Tunisian Turner Syndrome patients: familial versus sporadic cases.

OBJECTIVE: To explore unusual association between Turner Syndrome (TS) and Hypopituitarism in a Tunisian cohort. METHODS: We reported 6 patients with TS associated to Hypopituitarism, including three familial cases except the fourth sister who showed only a TS phenotype. Biochemical analysis, resonance magnetic imaging and cytogenetic analyses were performed. RESULTS: The average age of our patients was 17.2 years (11-31 years). They were all referred for short stature and pubertal delay, except for the fourth sister who presented spontaneous puberty with the integrity of the pituitary axis and the presence of an X ring chromosome. Karyotype analysis showed monosomy in 3 cases and a mosaic TS in the 3 remaining cases, including one patient with abnormal X chromosome structure. Somatotropic and corticotropic deficiencies were confirmed in 2 sporadic cases while the gonadotropic and thyrotropic axes were spared. In contrast; familial cases were consistently affected by the integrity of the corticotropic axis. MRI showed pituitary hypoplasia in all familial cases and pituitary stalk interruption syndrome in only one sporadic case. No correlation was found between the chromosome formula and the anterior pituitary involvement. CONCLUSION: Co-segregation of congenital Hypopituitarism with pituitary hypoplasia and X chromosome aberrations could imply a molecular anomaly of transcription factors responsible for the differentiation and development of pituitary cells such as PROP1, POUF1, Hesx1, Lhx3, Lhx4. The etiopathogenic link between X chromosome abnormalities and the occurrence of Hypopituitarism remains unclear; however, the progress of molecular biology may clarify the interrelation between transcription factors and sex chromosome segregation abnormalities.

[General practitioners' management of childhood asthma in Sfax, Tunisia]. / Prise en charge de l'asthme de l'enfant par le médecin de première ligne au Gouvernorat de Sfax, Tunisie.

AIMS: To study primary care physicians' attitudes toward childhood asthma management and their adherence to international guidelines. METHODS: Cross-sectional, descriptive and analytical survey conducted among 400 primary care physicians practicing in the governorate of Sfax. Data collection was done through a self-administered questionnaire with 36 questions. RESULTS: the participation rate was 53.75%. The average age was 49.72years and the sex ratio=1.52. 56.3% reported that they assisted in childhood asthma medical education between 2019 and 2020. Poor knowledge was found in 53.3% of practitioners. It concerns in 60.5% of cases the long-term asthma treatment. We found that 49.8% of doctors did not use the GINA guidelines in their daily practice. These guidelines were considered too complex by 45.8%. Oral salbutamol was prescribed by 10.2% of physicians in childhood asthma exacerbation and 64.2% antibiotics as therapy for childhood febrile asthma exacerbation. The practice of prescribing antihistamines as long-term therapy is still present in 28.8% of physicians. In front of exercise-induced asthma, sports exemptions were given by 33% of participants. Adherence to asthma guidelines was found in 34,41%. Physicians who are aged between 35 and 45years and who used GINA guidelines had better childhood asthma management score than other physicians. CONCLUSION: Despite guidelines, childhood asthma is still underdiagnosis and undertreated. Our study revealed difficulties faced by primary care physicians in the management of childhood asthma.

Relationship between electropherotypes and VP7/VP4 genotypes of group A rotaviruses detected between 2000 and 2007 in Tunisian children.

BACKGROUND: Rotaviruses are the most frequent agents associated with diarrhoea in children worldwide. Analysis of mobility of the 11 segments of genomic RNA by polyacrylamide gel electrophoresis (PAGE) yields a pattern which is characteristic for a particular rotavirus isolate. The group A rotaviruses can be further characterized by analysis of VP7 and VP4 genes specificities, responsible for rotavirus classification into G and P genotypes, respectively. The aim of the present study was to detect a relationship between electropherotype pattern and molecular characteristics of the rotavirus strains. MATERIAL AND METHODS: Were analyzed 278 rotavirus-positive specimens by PAGE and G/P-genotyped by multiplex semi-nested RT-PCR. Pearson's correlation tests were used for statistical analysis. RESULTS: Twelve different electropherotypes were visualized, eight with a long profile (186 cases) and four with a short one (87 cases). Concerning VP7 types, G2 viral strains were found to be predominant and were detected in 91 specimens (32.7%). Strains with G1, G3, G4, G8 and G9 specificities were detected in 62 (22.3%), 82 (29.5%), 13 (4.7%), two (0.7%) and seven cases (2.5%), respectively. The results of VP4 genotyping showed a predominance of P[8] genotype which comprised half of the strains identified (139 cases, 50%). VP4 P[4], P[6] and P[11] were found in 83 (29.9%), 31 (11.1%) and 11 (4.0%) specimens, respectively. A high rate of mixed strains was also found (1.8% mixed electropherotypes, 7.6% G-mixed and 5% P-mixed strains). Electropherotype pattern of rotavirus strains was significantly correlated with VP7 genotype (p=0.018) and with VP4 genotype specificities (p<0.001).

[Evolution of group A Rotavirus strains circulating in Tunisia over a 3-year period (2005-2007)]. / Évolution des souches de Rotavirus du groupe A en circulation en Tunisie sur une période de trois ans (2005-2007).

BACKGROUND: Rotaviruses are the most frequent agents associated with diarrhoea in children worldwide. Analysis of mobility of the 11 segments of genomic RNA by polyacrylamide gel electrophoresis (PAGE) yields a pattern which is characteristic for a particular rotavirus isolate. The group A rotaviruses can be further characterized by analysis of VP7 and VP4 genes specificities, responsible for rotavirus classification into G and P genotypes, respectively. The aim of the present study was to determine the evolution of group A Rotavirus strains circulating in Tunisia over a 3-year period (2005-2007). MATERIAL AND METHODS: A total of 1503 stool samples collected from children less than five years old, consulting or hospitalised in Tunisia for diarrhoea between 2005 and 2007, were screened for the presence of group A Rotaviruses. Rotavirus-positive specimens were further analyzed by PAGE and G/P-genotyped by multiplex semi-nested RT-PCR. RESULTS: Rotaviruses were detected in 323 stool samples over 1503 (21 %). Long electropherotypes predominated in Tunisia during the whole period of study (N=158 vs N=82 short electropherotypes). VP7 genotyping showed the cocirculation of five different genotypes: G1, G2, G3, G4 and G9. VP4 typing detected four different P-genotypes: P[8], P[4], P[6] and P[11]. Rotavirus strains with G3P[8] specificity were predominating in Tunisia in 2005 and 2006, replaced by G2P[4] strains in 2007.

[Aplasia cutis congenita of the scalp (5 observations)]. / Aplasia cutis congenita du vertex (5 observations).

UNLABELLED: Aplasia cutis congenita (ACC) is an uncommon congenital malformation. It is characterized by defects of the skin that occur most frequently on the scalp along the midline, but can also be localized on the trunk, face and limbs, usually with a symmetrical distribution. When it is localized in the skull, it can extend to the dura mater, with only the thin pia mater to protect the brain. PATIENTS AND METHODS: We report a retrospective study during a period of 10 years and we report 5 cases of ACCV hospitalized in the pediatric service in CHU Hédi Chaker and in maxillo-facial surgery service in CHU Habib Bourguiba, Sfax. We studied the epidemiologic, clinical, and therapeutic aspects in our patients. RESULTS: The average age at the admission was 5 days (2-8 days). A consanguinity was found in 2 cases. The clinical examination revealed cutaneous and osseous structures aplasia located in frontoparietal zone in 3 patients and in parieto-occipital zone in a patient. A hypoplasia of the toes was noted in 3 cases and a hypoplasia of the 3rd finger of the 2 hands in a case. Plain X-ray skull (3 cases) showed the osseous defect in all the cases. The cerebral IRM (2 cases) showed osseous and cutaneous defect in two cases and a lipome of the corpus callosum in one patient. A surgical repair using a cutaneous graft was performed for 3 patients. A patient died on the 16th day of life from a haemorrhage of the longitudinal sinus. The evolution was favourable in 4 cases with a cicatrisation of good quality but with subsequent alopecia. CONCLUSION: ACC of the scalp is a rare and often sporadic affection. Our experience confirms that fatal bleeding from the longitudinal sinus can occur during the 1st weeks of life.

[Moyamoya and Down syndrome: about 2 cases]. / Syndrome de Moyamoya et trisomie 21 : à propos de 2 cas.

Moyamoya syndrome has rarely been reported in association with Down syndrome. We report on 2 cases in 3-year-old and 6-year-old female children with Down syndrome, who presented with neurological deficit. Imaging (magnetic-resonance angiography and digital-subtraction angiography) revealed the classical Moyamoya pattern. The neurological deficits persisted in both cases. One patient has developed epilepsy.

CREM variant rs17583959 conferred susceptibility to T1D risk in the Tunisian families.

Type 1 diabetes mellitus (T1D) is a chronic autoimmune disease caused by the destruction of insulin-producing pancreatic ß-cells by autoreactive T cells. Studies in animal models, such as the non-obese diabetic (NOD) mouse reveal that this disease is under the control of several genes that encode molecules implicated in regulation of transcription factors and in T cell activation. In order to underline the role of the genes involved in this regulation pathways, we investigated, using the Sequenom MassARRAY platform, 13 single-nucleotide polymorphisms (SNPs) belonging to CREM, IRF5, STAT4, and STAT5a/b genes in 59 T1D Tunisian families. In the current study, we identified an association with rs17583959 (allele G; Z score=2.27; p=0.02; Genotype GG: score=1.96; p=0.04) of CREM gene. In LD analysis a strong LD between the 3 CREM variants (Block 1) was detected; rs2384352 was in complete LD with rs1148247. When haplotypes were constructed between CREM polymorphisms (rs1148247, rs17583959, rs2384352), AGA haplotype (H2) was significantly over-transmitted from parents to affected offspring (Z score=2.988; P=0.002) and may confer a risk for T1D disease. Whereas, AAG haplotype (H5) (Z score=-2.000; p=0.045) was less transmitted than expected to affected children suggesting its protective effect against T1D pathology. No significant association in IRF5, STAT4, and STAT5a/b genes were observed. In conclusion, this study shows an eventually involvement of CREM gene in the development of T1D pathology in Tunisian families. These facts are consistent with a major role for transcription factor genes involved in the immune pathways in the control of autoimmunity. Further researches of association and functional analysis across populations are needed to confirm these findings.

[Cowden's disease: a new paediatric observation]. / La maladie de Cowden: une nouvelle observation pédiatrique.

We report on a paediatric observation of Cowden's disease in a 6-year-old child. Familial steroid-resistant nephrotic syndrome was associated to papulous and papillomatous lesions of gingiva and oral mucosa, multiple hamartoma of the back and of upper limbs, facial dysmorphism and follicular thyroid cancer. Thyroid cancer evolved favorably after surgical treatment, radioactive iodine and L-thyroxin supplementation. Nephrotic syndrome evolved to chronic renal insufficiency after 11 years. The early diagnosis of Cowden's disease, or multiple hamartoma syndrome, allows a careful monitoring of the patients who are facing the risk of cancer transformation, which is the principal complication of the condition.

Association of TCR/CD3, PTPN22, CD28 and ZAP70 gene polymorphisms with type 1 diabetes risk in Tunisian population: family based association study.

Type 1 diabetes (T1D) is caused by an immune-mediated destruction of the insulin-producing ß-cells. Several studies support the involvement of T cell activation molecules in the pathogenesis of T1D. In order to underline the role of the genes involved in this activation pathway, we investigated, using the Sequenom MassARRAY platform, 45 single-nucleotide polymorphisms (SNPs) belonging to TCR/CD3, CD28, ZAP70, and PTPN22 genes in 59 T1D Tunisian families. In the current study, we identified an association with rs706 (Z score=2.782; p=0.005) of TCRß gene. We also demonstrated that rs10918706 in the intron of the CD3z gene was associated with increased risk of T1D (Z score 2.137; p=0.032). In the same region, rs2949655 (Z score=2.101; p=0.035) and rs1214611 (Z score=4.036; p=0.00005) showed a genotype association with the risk of T1D. When haplotypes were constructed, GAA haplotype displayed significant association with T1D (Z score=2.135; p=0.032), while GGA haplotype (Z score=-1.988; p=0.046) was negatively associated with the disease. We also identified an association with rs3181096 (Z score=2.177; p=0.029), rs17695937 (Z score =2.111; p=0.034) and rs2488457 (Z score=2.219; p=0.026), respectively of CD28, ZAP70 and PTPN22 genes. In addition, our results suggest a significant effect on T1D susceptibility for AC (Z score=2.30; p=0.02) and CTGGC (Z score=2.309, p=0.02) haplotypes of ZAP70 and PTPN22 genes, respectively. While, the GTCT (Z score=-2.114, p=0.034) and CTAGG (Z score=-2.121, p=0.033) haplotypes of CD28 and PTPN22 genes, may confer protection against T1D. These findings confirm the role of PTPN22 and CD28 involved in the T cell activation pathway in the development of T1D in Tunisian families. Interestingly, ZAP70 and TCRß/CD3z seem to contribute to the susceptibility to the disease in our population. However, this finding has to be confirmed in further studies.

[Hypoplasia of the internal carotid artery: a rare cause of cerebral ischemic stroke in children]. / L'hypoplasie de la carotide interne : une cause rare d'accident vasculaire cérébral ischémique chez l'enfant.

Hypoplasia of the carotid arteries is a rare congenital anomaly which, when symptomatic, presents as cerebral ischemia or hemorrhage. We report a case of hypoplasia of the carotid arteries revealed by cerebral ischemic stroke in an infant with hereditary spherocytosis. The diagnosis was confirmed by MR angiography. We describe this rare cause of stroke in children and the characteristics of its association with hereditary spherocytosis.

Descriptive analyses of Turner syndrome: 49 cases in Tunisia.

Turner syndrome is linked to the absence or abnormality of one of the X chromosome leading to haplo-insufficiency of genes involved in the development and maintenance of the ovarian stock in women. We report the results of a 21-year retrospective study, conducted in 49 patients with Turner syndrome. The purpose of this study was to establish the clinical, hormonal, cytogenetic and evolutive pattern of a Tunisian population with Turner syndrome and to search for correlations between genotype and phenotype. The average age of our patients at diagnosis was 14 years (1 day-42 years). Twenty-four percent of them were diagnosed in adulthood (greater than or equal to 20 years). Turner syndrome was diagnosed later in the case of mosaicism (P=0.001). Short stature was present in 85% of cases; it was more frequent among the youngest and monosomics. The dysmorphic syndrome was observed in 85% of cases; it was significantly more frequent in monosomics (P=0.003). Delayed puberty was present in 62.4% of cases, it was almost constant in monosomics (P=0.05). The loss of ovarian function was more severe in case of monosomia compared to other forms (P=0.04). Our results report a high frequency of autoimmune diseases (18/46 cases) including dysthyroidism (eight cases). Hepato biliary affections were more frequent in mosaicism compared to monosomy. The average final height was greater even in mosaicism estimated at 150.5 cm compared to 141 cm in monosomics and 138.8 cm in mosaics with abnormal structures.

[Factor VII deficiency revealed by intracranial hemorrhage]. / Déficit congénital en facteur VII de la coagulation, révélé par une hémorragie cérébrale.

Constitutional factor VII deficiency is a hereditary disease with recessive autosomic transmission. Its incidence is estimated to be 1/1,000,000 in the general population. We report a case of severe factor VII deficiency in infancy revealed by an intracranial hemorrhage in a 2-month-old infant. We describe the clinical, biological and therapeutic characteristics of this disease.