Response to growth hormone therapy in ring chromosome 15: Review and evidence from a new case on possible beneficial effect in neurodevelopment.

Type 1 Insulin-like Growth Factor Receptor(IGF1R) plays a fundamental role in normal growth and development. Its disruption is usually characterized by severe intrauterine and postnatal growth retardation, microcephaly and neurodevelopmental delay.The efficacy of recombinant human growth hormone treatment remains a challenge for children with IGF1 resistance and pathogenic mutations of IGF1R, with limited data in patients carrying the most severe form of IGF1R defect, the ring chromosome 15. SUBJECT AND METHOD: We tested a high dose of rhGH in a new patient with ring chromosome 15, as confirmed by karyotype and CGH array. We performed a systematic review, and all published r(15) syndrome cases treated by growth hormone(GH) up to April 2023 were searched, and their response to GH therapy was recorded and summarized. RESULTS: Twelve patients with ring chromosome 15 received GH therapy according to a literature review. We expand the spectrum by the 13th case treated by GH, and we report an impressive improvement in intellectual performance and progressive catch-up growth after 5 and 20 months of follow-up. By introducing our new case in the analysis, the sex ratio was 3:10, and GH therapy was started at the age of 5.5 (3/9.4) (years) for an age of diagnosis of 4.75 (1.3/9.5) (years). The height before GH therapy was -5.1(-5.9/-4.1) SDS. The median duration of treatment was 1.7(0.9/2) (years), with a median height gain of 1(0.3/1.8) SDS and an improvement in growth velocity of 4.1(2.8/5.3) (cm/year). CONCLUSION: GH seems to be effective for r(15) syndrome patients with short stature.

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.

Parental self-medication with antibiotics in a Tunisian pediatric center.

INTRODUCTION: Self-medication of antibiotics among children is a very common problem in Tunisia. Its prevalence isn't well established. The aims of this study are to evaluate parents' knowledge concerning antibiotic use, and identify the factors associated with this problem. PATIENTS AND METHODS: We conducted a cross-sectional study over a one year period (between August 2019 and July 2020). Data collection was performed using a questionnaire guided interview. We included parents of children consulting or hospitalized in the pediatric department of the university hospital Taher Sfar in Mahdia. RESULTS: A total of 354 parents were included with an average age of 36.4±9.2 years. The average knowledge score was 2±1.3 points. In fact, 61.6% of the parents had poor knowledge about antibiotics. The frequency of non-prescription antibiotics use among children was 20.6%. Amoxicillin was the most used antibiotic (72.6%). Sore throat, important fever and flu-like symptoms were the main symptoms justifying non-prescription antibiotic use among our pediatric population in 60.3%, 34.2% and 23.3% of cases respectively. The main reason of self-medication was the fact that the same antibiotic was once prescribed to treat the same symptoms (58.9%). The used antibiotic came from an old prescription for the same child in 57.5% of the cases and was recommended by the pharmacist in 39.7% of the cases. After multivariate analysis, the factors associated with parental self-medication with antibiotics were: the advanced parent's age, the ability to name an antibiotic and knowledge's score>2. CONCLUSION: Our study confirmed that parental knowledge about antibiotic use is low. In fact, the government should from one hand, organize antibiotic delivery and prohibit off the counter sells and in the other hand promote the education of the public through different procedures to stop this major health problem.

Kawasaki disease shock syndrome complicated by coronary aneurysms: a case report.

Kawasaki disease is a generalized systemic vasculitis, which primarily affects medium-sized arteries. Kawasaki disease shock syndrome is a rare but severe presentation of this disease. This report describes a case of delayed diagnosis of Kawasaki disease shock syndrome in a 13-year-old boy who presented with cervical adenophlegmon, persistent fever, injected conjunctiva, rash, and hypotension. Echocardiography revealed the presence of bilateral coronary aneurysms. Early recognition of Kawasaki disease shock syndrome can be difficult; however, delay in diagnosis and treatment can increase the risk of coronary artery disease.

Orbital complication of acute ethmoiditis: A Tunisian paediatric cross sectional study.

OBJECTIVE: The anatomical and developmental particularities of sinus cavities in paediatric population lead acute ethmoiditis to be the earliest form of sinusitis in children. Orbital complications are frequent and could lead to visual and neurological impairment. This study investigated the clinical, biological and radiological features of orbital complications. We identified the predictive factors of severe ophthalmological lesions and/or associated cerebral complications of acute ethmoiditis. DESIGN AND METHODS: This cross sectional study included all patients identified as having orbital extension of acute ethmoiditis in the database of a single academic paediatric care centre over a period of 14 years. All orbital and cerebral Scans of the included patients were reviewed and the cohort was classified using Chandler's classification as having less severe lesions (Chandler's 1 and 2) or more serious lesions (Chandler's 3, 4 and 5). RESULTS: In total, 16 patients (12 girls and 4 boys) were included among 39 consecutives cases of ethmoiditis recessed with a complication rate of 41%. Average consultation delay was 4.88 days. The mean age was 4.37 years. Fever was objectified in 13 cases (81%). Six patients (37.5%) had exophthalmos. Orbital extension spectrum was: stage I (n = 4, 25%), stage II (n = 4, 25%), stage III (n = 6, 37.5%), stage IV (n = 1, 6.5%), stage V (n = 1, 6.5%) and intra cranial extension was associated in two cases. Univariate analysis showed that fever, exophthalmos, ophthalmoplegia, positive CRP, age and white blood cells count were not associated with more severe lesions in the CT scan. Initially, all children received intravenous antibiotic treatment. Association of multiple antibiotics was prescribed in 75% of the cases. With 21.07 days ±â€¯5.51 days as a total treatment duration. Only Four patients underwent surgical treatment. CONCLUSION: Orbital complications of ethmoiditis are frequent. No clinical or biological criteria seem to predict the severity of orbital lesions. Both orbital and brain CT scan could help detect eventual complications on time to adapt antibiotic treatment and eventually bring forward surgical intervention.

Phenotypic variability in Tunisian PFIC3 patients harboring a complex genotype with a differential clinical outcome of UDCA treatment.

INTRODUCTION: Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a chronic autosomal recessive disorder characterized by a wide spectrum of clinical severity generally related to the degree of pathogenicity of the causal sequence variation in ABCB4 gene. PATIENTS AND METHODS: The present study reports the molecular investigation by Next Generation Sequencing (NGS) of five related patients with PFIC3 disease followed by bioinformatic analysis. A biochemical follow-up is also performed to assess the response of the ursodeoxycholic acid treatment. RESULTS: The molecular results revealed complex genotype in homozygous state in all patients including a pathogenic c.1436C > T (P479L) variation in the ABCB4 gene and two well-known polymorphisms, the V444A in ABCB11 gene and the D19H in the ABCG8 gene. Although the presence of the same genetic background, all patients present the disease at different ages and clinical signs with a variable degree of clinical severity at diagnosis. Additionally, a differential outcome to the treatment has been pointed out. CONCLUSION: Our results provide evidence regarding the putative intervention of modifier factors in the phenotypic variability reported for the first time in the PFIC3 disease and highlight the importance of an early administration of the UDCA as a good solution to ovoid the disease progression.

Poikiloderma with neutropenia in a Tunisian patient with a novel C16orf57 gene mutation.

Poikiloderma with neutropenia (PN) is a genodermatosis characterized by poikiloderma, permanent neutropenia, recurrent infections, nail abnormalities, and palmoplantar hyperkeratosis. We report the case of a Tunisian patient with PN. Skin lesions started from the face and spread to the extremities and trunk. Neutropenia was initially periodic and concomitant with infections periods. DNA analysis identified a novel homozygous deletion of a 1-bp (c.161delC, p.P54RfsX60) in the C16orf57gene, presumed to be causative. This report presents the variability of the clinical manifestations and evolution of PN and emphasizes the importance of studying other patients with PN to better delineate mutations profile among populations.

Bilateral orbital myeloid sarcoma as initial manifestation of acute myeloid leukemia.

BACKGROUND: Granulocytic sarcoma is a rare orbital complication of acute leukemia. It concerns primarily children under 10 years of age suffering from primitive acute myeloid leukemia. The diagnosis is made by clinical examination, computed tomography and confirmed by haematological investigations. The treatment approach is based on chemotherapy associated with intravenous steroid therapy. CASE REPORT: We report the case of a 6-year-old girl who presented with bilateral proptosis revealing acute myeloid leukemia. The patient was treated by a combination of chemotherapeutic drugs in two phases, associated with intravenous steroids. After a follow-up period of 24 months, the patient was in complete remission. CONCLUSION: The diagnosis of granulocytic sarcoma should be considered in any orbital mass of uncertain origin, particularly if it is bilateral. Special stains and immunohistochemistry play an important role in the diagnosis.

Genetic heterogeneity of megaloblastic anaemia type 1 in Tunisian patients.

Megaloblastic anaemia 1 (MGA1) is a rare autosomal recessive condition characterized by selective intestinal vitamin B12 malabsorption and proteinuria. More than 200 MGA1 patients have been identified worldwide, but the disease is relatively prevalent in Finland, Norway and several Eastern Mediterranean regions. MGA1 is genetically heterogeneous and can be caused by mutations in either the cubilin (CUBN) or the amnionless (AMN) gene. In the present study we investigated the molecular defect underlying MGA1 in nine Tunisian patients belonging to six unrelated consanguineous families. Haplotype and linkage analyses, using microsatellite markers surrounding both CUBN and AMN genes, indicated that four out of the six families were likely to be linked to the CUBN gene. Patients from these families were screened for the Finnish, Mediterranean and Arabian mutations already published. None of the screened mutations could be detected in our population. One family showed a linkage to AMN gene. Direct screening of the AMN gene allowed the identification of the c.208-2A>G mutation, previously described in a Jewish Israeli patient of Tunisian origin and in Turkish patients. This suggests that the c.208-2A>G mutation may derive from a single Mediterranean founder ancestor. For the last family, haplotype analysis excluded both CUBN and AMN genes, suggesting the existence of a third locus that may cause MGA1.

[Severe community acquired pneumonia due to Staphylococcus aureus in children. About two cases]. / Pneumonies staphylococciques graves de l'enfant. A propos de deux observations.

The staphylococcal pneumonia is the prerogative of the infant but rare cases were observed in the childhood. We report the observation of two children aged respectively of six years and three years and a half having presented a particular form of severe staphylococcal pneumonia apart from any context of immunodepression. The identification of the particular strains producing toxins Like the Panton and Valentine leukocidin constitutes the first stage of the comprehension of this atypical form of pneumonia. Through these observations and with a review of literature we underline the specific clinical and biological aspects of this form.