Turner syndrome: results of the first Tunisian study group on Turner syndrome (TuSGOT).

OBJECTIVES: Early diagnosis in Turner syndrome is desirable to optimize growth and puberty and yet, it is often made late. Here, we aim to identify age at diagnosis, clinical features at presentation and potential strategies to improve the care of TS girls. METHODS: Retrospective study, including patients from 14 care centers across Tunisia including neonatal and pediatric care units, adult endocrinology and genetics departments. RESULTS: We identified 175 patients with TS, karyotype showing 45, xmonosomy in 83(47.4 %) with mosaicism in 37(20 %). Mean ± SD, median (range) age at diagnosis available in 173 patients was 13 ± 9.2,12 (birth-48) years. The diagnosis was antenatal in 4(2.3 %), from birth-2 years in 14 (8 %)with lymphoedema (8)and dysmorphic features (9),2-12 years in 53 (35.5 %) including 35 with short stature, 13-18 years in 43(28.8 %) with short stature(28) and delayed puberty(14) and 35(23.5 %) after 18 years, related to ovarian insufficiency (20) and short stature (11). The associated malformations were cardiac in 14 (12.8 %), renal in 22 (19.6 %). A total of 56 girls (32 %) had proven gonadal dysgenesis and 13 (7 %) had otological problems. Parental height was available in 71 girls (40 %) of whom 59 were below the lower end of parental target range (LTR) (83 %). CONCLUSIONS: This first Tunisian multicenter study, the first African of its kind, reveals that more than half of Turner syndrome cases are diagnosed after the age of 12 years. Subsequently, national strategies for an earlier TS diagnosis are needed such as measuring and plotting parental heights as well as introducing a systematic height screening at 5 years in Tunisia with a view to carrying out a re-audit in five years' time.

Autoantibodies to Zinc Transporter 8 and SLC30A8 Genotype in Type 1 Diabetes Childhood: A Pioneering Study in North Africa.

Background: Type 1 diabetes (T1D) occurs as a result of insulin deficiency due to destructive lesions of pancreatic ß cells. In addition to classical autoantibodies (Abs) to islet cell antigens, antizinc transporter 8 Abs (ZnT8-Ab) have been recently described in T1D. Objective: As no data on ZnT8-Ab in Tunisian patients has been reported, we aim to evaluate the relationships between ZnT8-Ab, ZnT8 coding gene (SLC30A8) promoter polymorphism, and T1D risk in newly diagnosed children. Methods: ZnT8-Ab were measured in the serum of T1D newly affected children (n = 156) who were admitted to the pediatric department of the Hedi Chaker University Hospital of Sfax. Rs13266634 was genotyped in T1D children and 79 of their first-degree parents. The SPSS software was used to analyze the serological data. Allelic association analysis was conducted with family-based association tests implemented in the FBAT program v1.5.1. Results: ZnT8-Ab was detected in 66/156 (42.3%) of T1D newly diagnosed children. Among them, 6 (9%) presented ZnT8-Ab as the only humoral marker. The inclusion of ZnT8-Ab increased the number of Ab-positive patients to 90% and reduced the negative ones by 27%. There was no evidence of any overtransmission of any allele of the rs13266634 C/T polymorphism from parents to affected T1D children, nor of any correlation with any clinical or serological parameter. After the T1D disease onset age adjustment, a significant association was observed with the C allele suggesting that it could have a susceptibility role. Conclusion: ZnT8-Ab appears as a relevant diagnostic marker for T1D in Tunisian children, especially at the onset of the disease as teenagers.

Congenital syndactyly: a retrospective study of 18 cases at the Department of Orthopaedic Surgery and Traumatology of the Habib Bourguiba University Hospital, Sfax, Tunisia.

Congenital syndactylies are frequent congenital malformations of the hand. They can be an isolated finding or they can be found in association with other polymalformative syndromes. Several surgical techniques used to treat them have been described in the literature. The most used is the dorsal commissural omega-flap technique. We here report a study of 18 patients with congenital syndactyly, with multiple involvement in several cases, whose data were collected at the Department of Orthopedics and Traumatology of Sfax (Tunisia). All patients were operated using the dorsal commissural omega-flap technique. We operated 42 commissures in 18 patients. The average age of patients was 7 years. Only 3 patients had syndromic forms. Six of these patients were operated in two stages. For scar quality, mean OSAS score was 11.47 (11.35 for simple types and 12 for complex types). All patients with complex types had long-term complications (100%). Six patients with simple types out of 14 had complications (42.85%). The management of congenital syndactylies is surgical. It is important to provide parents with accurate information on the essential role of follow-up appointments in order to avoid complications in the short and the long term.

Genetic diagnosis in Sudanese and Tunisian families with syndromic intellectual disability through exome sequencing.

BACKGROUND: Intellectual disability is a form of neurodevelopmental disorders that begin in childhood and is characterized by substantial intellectual difficulties as well as difficulties in conceptual, social, and practical areas of living. Several genetic and nongenetic factors contribute to its development; however, its most severe forms are generally attributed to single-gene defects. High-throughput technologies and data sharing contributed to the diagnosis of hundreds of single-gene intellectual disability subtypes. METHOD: We applied exome sequencing to identify potential variants causing syndromic intellectual disability in six Sudanese patients from four unrelated families. Data sharing through the Varsome portal corroborated the diagnosis of one of these patients and a Tunisian patient investigated through exome sequencing. Sanger sequencing validated the identified variants and their segregation with the phenotypes in the five studied families. RESULT: We identified three pathogenic/likely pathogenic variants in CCDC82, ADAT3, and HUWE1 and variants of uncertain significance in HERC2 and ATP2B3. The patients with the CCDC82 variants had microcephaly and spasticity, two signs absent in the two previously reported families with CCDC82-related intellectual disability. CONCLUSION: In conclusion, we report new patients with pathogenic mutations in the genes CCDC82, ADAT3, and HUWE1. We also highlight the possibility of extending the CCDC82-linked phenotype to include spastic paraplegia and microcephaly.

[Epidemiology of home accidents in childhood: experience in the Division of General Pediatrics in Southern Tunisia]. / Epidémiologie des accidents domestiques de l'enfant: expérience d'un Service de Pédiatrie Générale du sud tunisien.

Home accidents are a serious public health problem in Pediatrics. They are responsible for heavy morbidity and mortality in the paediatric population. We conducted a retrospective study of 231 cases of domestic accidents in childhood in the Division of General Pediatrics at the Hedi Chaker Hospital, Sfax over a period of 5 years (2008-2012). During the study period, we collected data from 231 domestic accidents. The study involved 124 boys (53.7 %) and 107 girls (46.3%). The average age of patients was 2 years, ranging from 1 day to 14 years; children under 4 years were the most exposed to home accidents (88.7%). Accidental poisonings were the most common accidents (105 cases). Caustics were the most common toxic agents (33 cases), followed by drugs (28 cases) and hydrocarbons (16 cases). Foreign body accidents were the second most common mechanism of injury (64 cases). They included 43 cases of inhalation of foreign bodies and 21 cases of foreign body ingestion. We recorded 28 cases of trauma, 25 cases were caused by a fall from a certain height. We noted 26 cases of scorpion envenomation, 5 cases of drowning, 2 cases of burn and a single case of electric shock. Accidental poisonings and foreign body accidents were the main home accidents noted during our study and the age group 1 -4 years was the most exposed to home accidents.

Hypoparathyroidism in children: a study of eight cases.

BACKGROUND: Hypoparathyroidism is a rare pediatric endocrine disease, which is caused by low circulating levels of PTH or insensitivity to its action in the target tissues. AIM: To report the clinical and biochemical characteristics and theoutcome of 8 patients with hypoparathyroidism. METHODS: We analyzed retrospectively the results of clinical, biochemical, radiological findings of patients with hypoparathyroidism diagnosed in pediatric department of Hedi Chaker Hospital during the period 1994-2013. RESULTS: Eight patients (5 females and 3 males) were diagnosed with hypoparathyroidism during 20 years's period. The median age at the onset of first symptoms was 17,5 months (15 days- 5 years and 10 months). Seizures were the most commonly presenting symptom and were seen in seven cases. Eight patients were diagnosed with hypoparathyroidism (Di-Georges syndrome: one case, Sanjad Sakati syndrome: 3 case, kearns sayre syndrome: 1 case, autoimmune polyendocrinopathy candidiasis- ectodermal dystrophy: one case, idiopathic hypoparathyroidism: two cases. Conventional treatment was based on calcium and vitamin D analogs. The average of follow up was 5 years. Nephrocalcinosis was noted in two patients. The death occurred in five patients; it was related to hypocalcaemia in one patient. CONCLUSION: The diagnosis of hyperparathyroidism is easy; it's established on the association of hypocalcaemia and hyperphosphatemia. Etiologic approach is based on molecular findings. Vitamin D analog treatment of hypoparathyroidism in children involves the challenge, of adjusting treatment dosage to minimize both symptomatic hypocalcemia and asymptomatic, but potentially kidney-damaging, hypercalciuria causing nephrocalcinosis and renal insufficiency.

Adverse Reactions Due to the Bacillus Calmette-Guerin Vaccine: Twenty Tunisian Cases.

BACKGROUND: Bacillus Calmette-Guérin (BCG) vaccine is a widely used vaccine. Management of local BCG complications differs between clinicians, and the optimal approach remains unclear. AIMS: We aim to describe the epidemiological, clinical and therapeutic aspects of the BCG vaccine side effects in Sfax. PATIENTS AND METHODS: This was a retrospective study of all the cases of BCG vaccine adverse reactions recorded in the Dermatology and Paediatrics Departments of Hedi Chaker University Hospital of Sfax over a period of 10 years (2005-2015). RESULTS: Twenty cases of BCG adverse reactions were notified during the study period. Actually, 80% of the patients presented local adverse reactions. The outcome was good in all the followed patients. The rate of disseminated BCG disease was 20%. Biological tests of immunity showed a primary immunodeficiency in three cases, whereas the outcome was fatal in two cases. CONCLUSION: BCG vaccine adverse reactions range from mild to severe. However, the management of benign local reactions remains unclear. Disseminated BCG disease must alert clinicians to the possibility of a primary immunodeficiency.

Factor XIII deficiency in south of Tunisia.

: Factor XIII deficiency is a rare autosomal recessive disorder of hemostasis characterized by a plasmatic factor XIII level less than 1% in homozygote and bleeding as of the youth. The aim of the study is to describe the clinical features and the outcome of the patients and to determine molecular characteristics. A retrospective study, was conducted on seven patients with factor XIII deficiency in the department of hematology and pediatrics, Hedi Chaker Hospital, Sfax, Tunisia during the period of 14 years (2001-2014). The activity of factor XIII in plasma of the patients was less than 1%. Seven patients from five unrelated families were recorded (four men and three women). Median age at diagnosis was 3.5 years. All patients had consanguineous parents. Six patients presented umbilical bleeding and only three patients had intracranial bleeding. Other bleeding features were seen, including skin and mucosal bleeding, muscular hematoma, and splenic rupture. Recurrent abortions were observed in one patient. The standard screening tests were normal. Genetic analysis identified two mutations interesting the subunit A of factor XIII. All patients received transfusion of fresh frozen plasma monthly. One patient was died because of intracranial hemorrhage.Factor XIII deficiency is a rare bleeding disorder which frequently increases in areas with high consanguinity. In our study, we identified a founder mutation. The prognosis of the disorder is related to hemorrhagic complications especially to life-threatening intracranial bleeding. Prophylaxis consists of factor XIII concentrate or recombinant factor XIII. If these are unavailable, fresh frozen plasma may be used.

Clinical and Genetic Characterization of Tunisian Children with Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets.

BACKGROUND: Hereditary vitamin D-resistant rickets (HVDRR) is an autosomal recessive disorder characterized by the early onset of rickets and is caused by mutations in the vitamin D receptor (VDR) gene. Some HVDRR patients also have alopecia. PATIENTS AND METHODS: We retrospectively studied the clinical features, laboratory findings, genetic defects, as well as responses to treatment in a series of children with HVDRR. RESULTS: Eight patients from 7 families met the inclusion criteria. Alopecia was noted in 7 patients. Two different homozygous mutations in the VDR gene were identified in 6 patients: the p.K45E mutation located in the DNA-binding domain (5 patients with alopecia) and a novel p.T415R mutation located in the ligand-binding domain. A p.E143del CYP24A1 mutation, in the gene encoding the 25-hydroxyvitamin D3-24-hydroxylase, was identified in 2 brothers carrying the VDR gene mutation p.K45E. Six patients were treated with intermittent intravenous calcium treatment via the peripheral route with a clear improvement in 5 cases. CONCLUSION: To the best of our knowledge, this is the first major series reporting on HVDRR in Tunisia. The same mutation (p.K45E) was found in 5 apparently unrelated affected individuals. We have also extended the mutation spectrum by studying 1 novel VDR mutation.

Febrile seizures: an epidemiological and outcome study of 482 cases.

INTRODUCTION: Febrile seizures (FSs) are the most common type of seizures seen in children. After the first FS, 3 to 12% of children develop epilepsy, and 30% of these patients present with recurrent FS. The purpose of this study was to describe the epidemiological aspects of FS in order to better define the long-term outcomes in children with first FS and to identify the risk factors associated with the recurrence of FS as well as the development of epilepsy. METHODS: A retrospective study of 482 children with FS was conducted from January of 2004 to December of 2009 in the pediatric department of Hedi Chaker University Hospital in Sfax, Tunisia. The medical records for each patient were first collected and then analyzed at a later time. RESULTS: The study included 482 children. Simple FSs were found in 55.2% of children, and complex FSs were observed in 44.8%. The mean duration for follow-up examinations was 2 years and 4 months, and ranged from 1 to 5 years. No deaths or permanent neurological deficits due to FSs were observed, and only six children (1%) developed epilepsy. A total of 57 children (11.7%) developed recurrent seizures. Our findings suggest that a family history of FS, young age at onset, and a low degree of fever were predictive of recurrent FSs. CONCLUSION: Children with FSs encounter a minor risk of mortality and morbidity. While recurrent seizures are observed in these children, only a minority of these patients develop epilepsy.