Excess of de novo variants in genes involved in chromatin remodelling in patients with marfanoid habitus and intellectual disability.

PURPOSE: Marfanoid habitus (MH) combined with intellectual disability (ID) (MHID) is a clinically and genetically heterogeneous presentation. The combination of array CGH and targeted sequencing of genes responsible for Marfan or Lujan-Fryns syndrome explain no more than 20% of subjects. METHODS: To further decipher the genetic basis of MHID, we performed exome sequencing on a combination of trio-based (33 subjects) or single probands (31 subjects), of which 61 were sporadic. RESULTS: We identified eight genes with de novo variants (DNVs) in at least two unrelated individuals (ARID1B, ATP1A1, DLG4, EHMT1, NFIX, NSD1, NUP205 and ZEB2). Using simulation models, we showed that five genes (DLG4, NFIX, EHMT1, ZEB2 and ATP1A1) met conservative Bonferroni genomewide significance for an excess of the observed de novo point variants. Overall, at least one pathogenic or likely pathogenic variant was identified in 54.7% of subjects (35/64). These variants fell within 27 genes previously associated with Mendelian disorders, including NSD1 and NFIX, which are known to be mutated in overgrowth syndromes. CONCLUSION: We demonstrated that DNVs were enriched in chromatin remodelling (p=2×10-4) and genes regulated by the fragile X mental retardation protein (p=3×10-8), highlighting overlapping genetic mechanisms between MHID and related neurodevelopmental disorders.

[Etiologic profile of digital necrosis in an internal medicine department]. / Profil étiologique des nécroses digitales dans un service de médecine interne.

BACKGROUND: Digital necrosis is a frequent event in vascular pathology. They are multiple etiologies and are the translation of a general or locoregional pathology. The aim of our study was to clarify the various causes of digital necrosis in an internal medicine department. METHODS: We conducted a retrospective study of 23 cases of digital necrosis collected in the internal medicine department of the hospital Habib Thameur over a period from January 1998 to April 2011 . RESULTS: There were 16 women and 7 men with mean age of 46 years. The cardiovascular risk factors were observed in 39.13% cases. Digital necroses were interested fingers in 73.91% and toes in 30.43% of the cases. The causes were dominated by the connective diseases. The treatment was symptomatic in all cases and etiologic in only two cases. CONCLUSION: In internal medicine, the causes are dominated by connectivites. The prognosis is especially functional. It remains unfavorable in spite of the improvement of the therapeutic and etiologic care.

Deadly cerebral ischemia due to carotid stenosis following a facial shot with a pellet gun: An autopsy case report.

INTRODUCTION: Facial gunshot wounds have devastating functional and aesthetic consequences for the patient. If associated with penetrating craniocerebral injuries, the prognosis is rather compromised even with appropriate medical and surgical treatment. Chop-off injuries with penetrating wounds constitute a challenging situation for the facial reconstructive surgeon in facial trauma. OBSERVATION: This case involved a 49-year-old man who sustained an accidental facial shot from a pellet gun. Radiological and clinical investigations revealed complex ballistic trauma to the maxillofacial region, with projectiles reaching the base of the skull. One of the projectiles migrated via the carotid canal towards a cerebral artery, leading to obstruction of the artery with cerebral infarction. An autopsy was performed which evaluated that the shooting distance was compatible with a long distance, causing the dispersion of lead grains with the absence of a wad inside the trauma site. CONCLUSION: In some cases of facial gunshot wounds, despite a complex and extensive lesion assessment, death may occur due to a neurological complication rather than sustaining hemodynamic shock, depending on the trajectory of the projectiles.

Idiopathic Granulomatous Mastitis Associated with Erythema Nodosum in a Pregnant Woman.

A 32-year-old woman at 17 weeks' gestation presented with fever and a 1-week history of an acute nodular eruption involving her legs, along with bilateral ankle and knee pain. She also had had a recurrent right breast abscess for 2 months for which she had been treated with oral antibiotics and surgical drainage, but with slight improvement. Cultures of the abscess showed no bacteria or fungi. She had no history of tuberculosis, sarcoidosis, trauma to the breast, or a family history of breast pathology. Cutaneous examination revealed multiple, tender, erythematous, subcutaneous nodules on her legs (Figure 1) and an ill-defined tender mass involving the inferior quadrant of the right breast without nipple discharge or retraction. There was a scar with drainage on her right breast (Figure 2). There were no regional lymphadenopathies. Left breast and left axilla examination was unremarkable. Significant laboratory findings included an erythrocyte sedimentation rate of 54 mm/hour (normal levels [NL] < 20 mm/hour), an elevated C reactive protein at 148 mg/L (NL < 5 mg/L), and a high level of white blood cells averaging 15,000 elements/mm3 (NL < 10,000/mm3).

Breast amyloidosis associated with Sjögren syndrome: A diagnostic pitfall in breast pathology.

BACKGROUND: Amyloidosis is an uncommon disorder characterized by the extracellular deposition of amorphous and insoluble proteins in an abnormal fibrillary configuration. Mammary amyloidosis is an unusual and easily overlooked diagnosis with an ambivalent presentation that could mimic breast cancer. CASE REPORT: We here report the case of 60-year-old Caucasian woman who presented to our surgical oncology department for clinically and radiologically suspicious breast mass. A fine needle biopsy was irrelevant, so we performed a lumpectomy. Final histology revealed an amyloid deposit and further workup was consistent with nodular cutaneous and breast AL amyloidosis associated with Sjögren's syndrome. CONCLUSION: Although rare, an awareness of the clinicopathologic characteristics of this easily overlooked entity is of great importance for breast surgeons.

Fast diagnostic of osteoporosis based on hair analysis using LIBS technique.

Currently, the reference method for the diagnose of the osteoporosis pathology is the Dual energy X-ray Absorptiometry (DXA) technique which assesses Bone Mineral Density (BMD). As a major public health problem, classified as such by the World Health Organization, it is necessary to develop new techniques that are more accessible, especially for developing countries. The objective of this work is to propose a new technique based on laser-induced breakdown spectroscopy (LIBS) using calcium and sodium in hair as a biomarker for the detection of osteoporosis pathology. The study involved 90 women aged 50 to 70 years divided in three groups, thirty women with osteoporosis, thirty women with osteopenia and thirty healthy women. The application of LIBS technique on their hair to correlate calcium and sodium lines with T-scores allows a quick and cheap screening of the disease. The results showed strong correlations between calcium lines and disease. We noted a negative correlation between the intensity of calcium and sodium lines. In addition to these results, we show that we were able to cluster the three groups using the emission lines of these two elements. All these results support the idea that the use of LIBS applied to hair to evaluate calcium and sodium elements as effective biomarkers for the detection of osteoporosis is a promising approach.

Managing mass disasters linked to the sinking of illegal migrant boats: experiences of the Sfax forensic medicine service.

Background: The sinking of illegal migrant boats has been unpredictable. It has resulted in mass disasters that cause deaths and attracts huge media attention, thus making it a medico-social emergency. Aims: This paper reports activities of the forensic medicine service in Sfax, Tunisia and describes the forensic management of mass disasters related to the sinking of illegal migrant boats as well as the main challenges. Methods: This is a retrospective, descriptive study that includes all cases of drowning deaths examined at the forensic department of Habib Bourguiba Hospital, Sfax, following the sinking of illegal migrant boats over a four-year period (October 2017 to September 2021). Results: During the study period, we received 539 corpses following the sinking of illegal migrant boats. The median number of deaths was 93 per year. There was a significant decrease in the number of victims in 2019 (13 victims), followed by a significant increase in 2020 (115) and 2021 (271). We noted two frequency peak periods in June and July, 31.4% and 20.8%, respectively. The victims were mostly male (67.5%) with a sex ratio of 2.08. Minors aged under 18 years were 5.8% and pregnant women were 2.4%. The majority (63.1%) of the victims were of sub-Saharan origin and there has been an increase in the number of victims from this region over the past two years. Samples were systematically collected for genetic investigation and 146 (27.1%) victims were identified. Conclusion: There have been significant advances in the identification of the victims of migrant boat sinking around the Tunisian coast, however, there are several challenges in providing information rapidly to the families of the victims to clarify the uncertainty about the fate of their missing loved ones.

Analysis of Dp71 contribution in the severity of mental retardation through comparison of Duchenne and Becker patients differing by mutation consequences on Dp71 expression.

The presence of variable degrees of cognitive impairment, extending from severe mental retardation to specific deficits, in patients with dystrophinopathies is a well-recognized problem. However, molecular basis underlying mental retardation and its severity remain poorly understood and still a matter of debate. Here, we report one of the largest study based on the comparison of clinical, cognitive, molecular and expression data in a large cohort of 81 patients affected with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) bearing mutations predicted to affect either all dystrophin products, including Dp71 or all dystrophin products, except Dp71. In addition to the consistent data defining molecular basis underlying mental retardation in DMD, we show that BMD patients with MR have mutations that significantly affect Dp71 expression or with mutations located in exons 75 and 76. We also show that mutations upstream to exon 62, with DMD phenotype, predicted to lead to a loss-of-function of all dystrophin products, except Dp71 isoform, are associated, predominantly, with normal or borderline cognitive performances. Altogether, these reliable phenotype-genotype correlations in combination with Dp71 mRNA and protein expression studies, strongly indicate that loss-of-function of all dystrophin products is systematically associated with severe form of MR, and Dp71 deficit is a factor that contributes in the severity of MR and may account for a shift of 2 SD downward of the intelligence quotient.

Salmonella osteomyelitis complicating aseptic osteonecrosis: Don't forget about the antiphospholipid syndrome.

Osteonecrosis in antiphospholipid syndrome is a diagnostic challenge for clinicians. Early diagnosis and intervention are important for better prognosis.

Epidemiological, clinical, and therapeutic characteristics of Behçet's disease: a monocentric study in Tunisia.

INTRODUCTION: to describe the epidemiological, clinical, therapeutic and evolving characteristics of Behçet´s disease and identify prognostic factors. METHODS: we have realized a retrospective, single-center study, conducted over a period of 26 years and including 130 patients presenting Behçet´s disease and hospitalized in an Internal Medicine Department. RESULTS: the mean age of the Behçet´s disease at onset was 30.3 ±8.8 years and that at diagnosis was 34.6 ±9.4 years. The sex ratio (male/female) was 2.5. The mean delay of diagnosis was 53.5 months. Oral aphthosis was constant. The frequency of the manifestations was: genital aphtosis 71.5%, pseudofolliculitis 84.6%, erythema nodosum 11.5%, positive pathergy test 50%, ocular disease 36.9%, venous thrombosis 30%, arterial disease 4.6%, joint damage 30.8%, neurological disease 19.2% and digestive disease 0.8%. The male gender was significantly associated with ocular involvement (p =0.02), venous disease (p =0.01) and occurrence of relapses (p =0.01). The mean follow up was 68.5 ± 77.3 months. The poor survival prognostic factors were male gender, ocular involvement, venous disease, cardiovascular disease, a duration of follow up ≤12 months and a diagnostic delay ≤ 24 months. Conclusion: improving the prognosis of Behçet´s disease requires a shortening of the time to diagnosis, multidisciplinary collaboration, intensive treatment of functional threats, regular monitoring, and patient adherence.

Myxofibrosarcoma of the leg: A diagnostic challenge.

We should keep in mind slowly growing malignancies when the lesion is located close to the synovial regions of the extremities. The diagnosis of certainty of myxofibrosarcoma is histological and is based on the demonstration of the myxoid matrix, fibroblastic cells with a curvilinear arrangement of the vessels.

Arterial Hypertension in Systemic Lupus Erythematosus: About 40 Cases.

The aim of this study was to determine the prevalence and the etiologic profile of hypertension (HTN) in systemic lupus erythematosus (SLE). A retrospective analysis was performed on 153 patients with SLE who attended our center for 16 years from January 2000 to December 2016. The diagnosis of SLE was established according to the classification criteria of the American College of Rheumatology in 1990. The prevalence of HTN in patients with SLE was 26.1% (40/153)' with an average delay of appearance of 21 months. There were 37 women and three men with a mean age of 46' eight years (20-70). HTN was associated with lupus nephritis (n = 8)' other renal impairments (n = 6)' and corticosteroid treatment (n = 20). Essential HTN was found in six cases. Cardiovascular factors associated with HTN were: diabetes (n = 14)' sedentary life (n = 15)' obesity (n = 12)' and dyslipidemia (n = 8). Main clinical manifestations associated with HTN were: arthralgia/arthritis (24 cases)' cutaneous involvement (22 cases)' and hematological manifestations (16 cases). Anti-phospholipid syndrome was found in 12 cases. Coronary artery disease' arteritis of lower limb' and transient ischemic attacks complicated the course of HTN in six patients. Angiotensin-converting-enzyme inhibitors were the most commonly used drug for treatment in this group. HTN was frequently associated with corticosteroid treatment in this study. We feel that the use of corticosteroids should be avoided as far as possible in all patients with SLE.

Predictive factors of the lupus nephritis in a Tunisian cohort.

INTRODUCTION: Renal involvement is a common and serious manifestation of systemic lupus erythematosus (SLE) and it is life-threatening. AIM: To identify the predictive factors of the lupus nephritis (LN). METHODS: A descriptive, analytical, single-centre, retrospective study of 115 patients with SLE (ACR 1997) was carried out in an internal medicine department for a period of 20 years from 1997 until 2017. LN was diagnosed by proteinuria ≥ 0.5 g /24h and / or urine sediment abnormality. Eighty patients did not have kidney damage during the follow-up and thirty-five developed renal involvement after SLE diagnosis. RESULTS: The univariate analysis retained several epidemiological, clinical and biological correlation parameters, according to the development of lupus nephritis, statistically significant. They are as follows, the male gender, the age of diagnosis of SLE less than or equal to 34 years, the presence of malar rash by the time of SLE diagnosis, naso/pharyngeal ulcerations, leucopoenia, positivity of anti-Sm antibody and low C3 complement.The multivariate analysis had found that age less than or equal to 34 years at the diagnosis of the SLE was the only predictive factor of the onset of LN (OR=5.1 and HR=3.4). CONCLUSION: Given the seriousness of the pathology and the complexity of its management, LN should be detected as soon as possible and must be treated appropriately by selecting the lupus population at risk for developing a serious LN.

Revised spectrum of mutations in sarcoglycanopathies.

To define the spectrum of mutations in alpha-, beta-, gamma-, and delta-sarcoglycan (SG) genes, we analyzed these genes in 69 probands with clinical and biological criteria compatible with the diagnosis of autosomal recessive limb-girdle muscular dystrophy. For 48 patients, muscle biopsies were available and multiplex western blot analysis of muscle proteins showed significant abnormalities of alpha- and gamma-SG. Our diagnostic strategy includes multiplex western blot, sequencing of SG genes, multiplex quantitative-fluorescent PCR and RT-PCR analyses. Mutations were detected in 57 patients and homozygous or compound heterozygous mutations were identified in 75% (36/48) of the patients with abnormal western blot, and in 52% (11/21) of the patients without muscle biopsy. Involvement of alpha-SG was demonstrated in 55.3% of cases (26/47), whereas gamma- and beta-SG were implicated in 25.5% (12/47) and in 17% (8/47) of cases, respectively. Interestingly, we identified 25 novel mutations, and a significant proportion of these mutations correspond to deletions (identified in 14 patients) of complete exon(s) of alpha- or gamma-SG genes, and partial duplications (identified in 5 patients) of exon 1 of beta-SG gene. This study highlights the high frequency of exonic deletions of alpha- and gamma-SG genes, as well as the presence of a hotspot of duplications affecting exon 1 of the beta-SG gene. In addition, protein analysis by multiplex western blot in combination with mutation screening and genotyping results allowed to propose a comprehensive and efficient diagnostic strategy and strongly suggested the implication of additional genes, yet to be identified, in sarcoglycanopathy-like disorders.