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Myhre syndrome (MS) is a developmental disorder characterized by typical facial dysmorphism, thickened skin, joint limitation and muscular pseudohypertrophy. Other features include brachydactyly, short stature, intellectual deficiency with behavioral problems and deafness. We identified SMAD4 as the gene responsible for MS. The identification of SMAD4 mutations in Laryngotracheal stenosis, Arthropathy, Prognathism and Short stature (LAPS) cases supports that LAPS and MS are a unique entity. The long-term follow up of patients shows that these conditions are progressive with life threatening complications. All mutations are de novo and changing in the majority of cases Ile500, located in the MH2 domain involved in transcriptional activation. We further showed an impairment of the transcriptional regulation via TGFβ target genes in patient fibroblasts. Finally, the absence of SMAD4 mutations in three MS cases may support genetic heterogeneity., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

PCR amplification on single cells is prone to allele drop-out (PCR failure of one allele), a cause of misdiagnosis in preimplantation genetic diagnosis (PGD). Owing to this error risk, PGD usually relies on both direct and indirect genetic analyses. When the affected partner is the sporadic case of a dominant disorder, building haplotypes require spermatozoon or polar body testing prior to PGD, but these procedures are cost and time-consuming. A couple requested PGD because the male partner suffered from a dominant Cowden syndrome (CS). He was a sporadic case, but the couple had a first unaffected child and the non-mutated paternal haplotype was tentatively deduced. The couple had a second spontaneous pregnancy and the fetus was found to carry the at-risk haplotype but not the PTEN mutation. The mutation was present in blood from the affected father, but at low level, confirming the somatic mosaicism. Ignoring the possibility of mosaicism in the CS patient would have potentially led to selection of affected embryos. This observation emphasizes the risk of PGD in families at risk to transmit autosomal-dominant disorder when the affected partner is a sporadic case.

Lipin-1 deficiency is associated with massive rhabdomyolysis episodes in humans, precipitated by febrile illnesses. Despite well-known roles of lipin-1 in lipid biosynthesis and transcriptional regulation, the pathogenic mechanisms leading to rhabdomyolysis remain unknown. Here we show that primary myoblasts from lipin-1-deficient patients exhibit a dramatic decrease in LPIN1 expression and phosphatidic acid phosphatase 1 activity, and a significant accumulation of lipid droplets (LD). The expression levels of LPIN1-target genes [peroxisome proliferator-activated receptors delta and alpha (PPARδ, PPARα), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), acyl-coenzyme A dehydrogenase, very long (ACADVL), carnitine palmitoyltransferase IB and 2 (CPT1B and CPT2)] were not affected while lipin-2 protein level, a closely related member of the family, was increased. Microarray analysis of patients' myotubes identified 19 down-regulated and 51 up-regulated genes, indicating pleiotropic effects of lipin-1 deficiency. Special attention was paid to the up-regulated ACACB (acetyl-CoA carboxylase beta), a key enzyme in the fatty acid synthesis/oxidation balance. We demonstrated that overexpression of ACACB was associated with free fatty acid accumulation in patients' myoblasts whereas malonyl-carnitine (as a measure of malonyl-CoA) and CPT1 activity were in the normal range in basal conditions accordingly to the normal daily activity reported by the patients. Remarkably ACACB invalidation in patients' myoblasts decreased LD number and size while LPIN1 invalidation in controls induced LD accumulation. Further, pro-inflammatory treatments tumor necrosis factor alpha+Interleukin-1beta(TNF1α+IL-1ß) designed to mimic febrile illness, resulted in increased malonyl-carnitine levels, reduced CPT1 activity and enhanced LD accumulation, a phenomenon reversed by dexamethasone and TNFα or IL-1ß inhibitors. Our data suggest that the pathogenic mechanism of rhabdomyolysis in lipin-1-deficient patients combines the predisposing constitutive impairment of lipid metabolism and its exacerbation by pro-inflammatory cytokines., (© 2013.)

Kabuki syndrome (KS) is a rare syndrome associating malformations with intellectual deficiency and numerous visceral, orthopedic, endocrinological, immune and autoimmune complications. The early establishment of a diagnostic of KS leads to better care of the patients and therefore prevents complications such as perception deafness, severe complications of auto-immune diseases or obesity. However, the diagnosis of KS remains difficult because based on the appreciation of facial features combined with other highly variable features. We describe a novel sign, namely the attenuation and/or congenital absence of the IPD crease of the third and fourth fingers associated with limitation of flexion of the corresponding joints, which seems to be specific of KS and could help the clinician to diagnose KS., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Discordant chromosomal anomalies in monozygotic twins may be caused by various timing issues of erroneous mitosis and twinning events. Here, we report a prenatal diagnosis of heterokaryotypic monozygotic twins discordant for phenotype. In a 28-year-old woman, ultrasound examination performed at 26 weeks of gestation, detected intrauterine growth restriction and unilateral cleft lip and palate in twin B, whereas twin A had normal fluid, growth and anatomy. Molecular karyotyping in twin B identified a 18q21.2qter deletion, further confirmed by FISH analysis on amniocytes. Interestingly, in twin A, cytogenetic studies (FISH analysis and karyotype) on amniocytes were normal. Genotyping with microsatellite markers confirmed the monozygosity of the twins. At 32 weeks of gestation, selective termination of twin B was performed by umbilical cord coagulation and fetal blood samples were taken from the umbilical cord in both twins. FISH analyses detected mosaicism in both twins with 75% of cells being normal and 25% harboring the 18qter deletion. After genetic counseling, the parents elected to terminate the second twin at 36 weeks of gestation. In postmortem studies, FISH analyses revealed mosaicism on several tissues in both twins. Taking into account this observation, we discuss the difficulties of genetic counseling and management concerning heterokaryotypic monozygotic twins., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Objective: To determine the frequency and types of renal malformations, and to evaluate renal function in a cohort of patients with Kabuki syndrome (KS)., Study Design: Renal ultrasound scans and plasma creatinine measurements were collected from a French cohort of 94 patients with genotyped KS. Renal function was evaluated based on the estimated glomerular filtration rate. A genotype-phenotype study was conducted for renal and urinary tract malformations., Results: Renal malformations were present in 22% of cases, and urinary tract anomalies were present in 15%. Renal malformations were observed in 28% of the MLL2 mutation-positive group and in 0% of the MLL2 mutation-negative group (P = .015). No correlation was found between the presence or absence of renal or urinary tract malformations and the location or type of MLL2 mutation. Renal function was normal except for 1 patient with a MLL2 mutation diagnosed in the first days of life and severe renal disease due to unilateral renal agenesia and controlateral severe hypoplasia that progressed to the terminal stage at age 2 years., Conclusion: Our study emphasizes the need for ultrasound and renal function screening in children diagnosed with KS., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objective: Because available biomarkers (rheumatoid factors [RF], anti-cyclic citrullinated autoantibodies [anti-CCP2], erythrocyte sedimentation rate at 1st hour [ESR]/C-reactive peptide [CRP] and bone erosions) are insufficient to predict rheumatoid arthritis (RA) structural damage, to determine whether synovium expression of greater or equal to 1 markers could constitute new prognostic factor(s)., Method: The study was conducted on 18 prospectively enrolled disease-modifying anti-rheumatic drug (DMARD)- and glucocorticoid-naïve, VErA cohort patients with very-early arthritis (median duration: 4months). Recorded at baseline were: clinical and biological (serum ESR, CRP, RF-isotypes, anti-CCP2, osteoprotegerin, receptor activator of nuclear κB-ligand [RANK-L] and cartilage oligomeric matrix protein [COMP] levels) data; synovium expression (HLA-DR, CD163, CD3, CD20, VEGF, osteoprotegerin, RANK-L, Bcl2 and global inflammation index) for a metacarpophalangeal joint-synovium biopsy. Baseline and 3-year hand-and-foot X-rays were graded with the van der Heijde-modified-Sharp score; the judgment criterion was its progression during follow-up. Pearson's product moment correlation statistics were used to test for association between paired samples., Results: A baseline, a significant relationship was found between erosive damage and markers of B-cell activation, notably the synovium CD20 expression (r=0.68; P=0.0001). Quantified by the modified-Sharp erosion score variation, the 3-year structural damage progression was significantly correlated with: serum levels of RF-IgG (r=0.75; P=0.0003), -IgM (r=0.69; P=0.001), anti-CCP2 (r=0.53; P=0.02) and RANK-L (r=0.61; P=0.007); synovium CD20 expression (r=0.70; P=0.001)., Conclusion: This analysis of the prognostic value of a large panel of synovium markers in a limited sample of prospectively followed, well-documented patients suggested that both synovial CD20 and serum RANK-L levels might be new predictors of structural damage progression in very-early RA., (Copyright © 2011 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Background: Recessive LPIN1 mutations were identified as a cause of severe rhabdomyolysis in pediatric patients. The human lipin family includes two other closely related members, lipin-2 and 3, which share strong homology and similar activity. The study aimed to determine the involvement of the LPIN family genes in a cohort of pediatric and adult patients (n = 171) presenting with muscular symptoms, ranging from severe (CK >10 000 UI/L) or moderate (CK <10 000 UI/L) rhabdomyolysis (n = 141) to exercise-induced myalgia (n = 30), and to report the clinical findings in patients harboring mutations., Methods: Coding regions of LPIN1, LPIN2 and LPIN3 genes were sequenced using genomic or complementary DNAs., Results: Eighteen patients harbored two LPIN1 mutations, including a frequent intragenic deletion. All presented with severe episodes of rhabdomyolysis, starting before age 6 years except two (8 and 42 years). Few patients also suffered from permanent muscle symptoms, including the eldest ones (≥ 40 years). Around 3/4 of muscle biopsies showed accumulation of lipid droplets. At least 40% of heterozygous relatives presented muscular myalgia. Nine heterozygous SNPs in LPIN family genes were identified in milder phenotypes (mild rhabdomyolysis or myalgia). These variants were non-functional in yeast complementation assay based on respiratory activity, except the LPIN3-P24L variant., Conclusion: LPIN1-related myolysis constitutes a major cause of early-onset rhabdomyolysis and occasionally in adults. Heterozygous LPIN1 mutations may cause mild muscular symptoms. No major defects of LPIN2 or LPIN3 genes were associated with muscular manifestations.

We report 2 cases of fatal rhabdomyolysis in children carrying an LPIN1 mutations preceded by similar electrocardiogram changes, including diffuse symmetrical high-amplitude T waves. Our report underlines the severity of this disease and the need for active management of episodes of rhabdomyolysis in a pediatric intensive care unit., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Acrodysostosis is a rare autosomal-dominant condition characterized by facial dysostosis, severe brachydactyly with cone-shaped epiphyses, and short stature. Moderate intellectual disability and resistance to multiple hormones might also be present. Recently, a recurrent mutation (c.1102C>T [p.Arg368*]) in PRKAR1A has been identified in three individuals with acrodysostosis and resistance to multiple hormones. After studying ten unrelated acrodysostosis cases, we report here de novo PRKAR1A mutations in five out of the ten individuals (we found c.1102C>T [p.Arg368(∗)] in four of the ten and c.1117T>C [p.Tyr373His] in one of the ten). We performed exome sequencing in two of the five remaining individuals and selected phosphodiesterase 4D (PDE4D) as a candidate gene. PDE4D encodes a class IV cyclic AMP (cAMP)-specific phosphodiesterase that regulates cAMP concentration. Exome analysis detected heterozygous PDE4D mutations (c.673C>A [p.Pro225Thr] and c.677T>C [p.Phe226Ser]) in these two individuals. Screening of PDE4D identified heterozygous mutations (c.568T>G [p.Ser190Ala] and c.1759A>C [p.Thr587Pro]) in two additional acrodysostosis cases. These mutations occurred de novo in all four cases. The four individuals with PDE4D mutations shared common clinical features, namely characteristic midface and nasal hypoplasia and moderate intellectual disability. Metabolic screening was normal in three of these four individuals. However, resistance to parathyroid hormone and thyrotropin was consistently observed in the five cases with PRKAR1A mutations. Finally, our study further supports the key role of the cAMP signaling pathway in skeletogenesis., (Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Neonatal renal venous thrombosis (NRVT) is a rare disease, with variable consequences on kidney function. We report a retrospective study of 9 newborns with NRVT admitted to our hospital from 1996 to 2005. The median age at diagnosis was 2 days (range, 1-10 days). In 7 patients, diagnosis was suspected based on one classical clinical or biological sign and was confirmed by ultrasound. Seven newborns had at least one known obstetrical or neonatal risk factor. NRVT was unilateral in three cases, was bilateral in 6 cases, and was associated with inferior vena cava thrombosis in 5 patients, with surrenal hemorrhage in 3 patients. Three patients did not receive specific treatment. The median delay between diagnosis and specific treatment was 20 h (range, 3-36 h). Three patients were treated by fibrinolysis, including 2 with bilateral NRVT, 2 newborns received heparins, and 1 patient was treated with a vitamin K antagonist. With a median evaluation time of 5 years and 2 months for 6 patients, 5 patients recovered their kidney function completely and the 6th child has moderate renal failure. It seems illusory to wait for randomized control studies to appreciate the potential long-term benefit of treatments on kidney function after a NRVT, whose bilateral forms appear to be more severe. A case-by-case approach appears better adapted. These results reinforce recommendations that suggest an early pediatric nephrologic follow-up for all newborns with a NRVT., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

We report five cases of abdomino-pelvic PEComas diagnosed in the last 10 years in the Rouen University Hospital. Four are hepatic and one is in a pelvic location which is unusual due to its strongly pigmented aspect. The tumors derived from "perivascular epithelioid cells" are rare. They are characterized by spindle or epithelioid cells in an immediate perivascular location. The immunochemistry is positive for HMB45, MelanA and smooth muscle Actin. The criteria for malignancy are infiltrative growth pattern, necrosis, high cellularity, high nuclear grade and mitotic activity. There are 8% of recurrence and 20% of metastasis (lung, bones, liver). This study presents the clinical, pathologic, immunohistochemical and molecular aspects of these PEComas and discusses the main differential diagnosis of the pigmented one., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Autosomal recessive LPIN1 mutations have been recently described as a novel cause of rhabdomyolysis in a few families. The purpose of the study was to evaluate the prevalence of LPIN1 mutations in patients exhibiting severe episodes of rhabdomyolysis in infancy. After exclusion of primary fatty acid oxidation disorders, LPIN1 coding sequence was determined in genomic DNA and cDNA. Among the 29 patients studied, 17 (59%) carried recessive nonsense or frameshift mutations, or a large scale intragenic deletion. In these 17 patients, episodes of rhabdomyolysis occurred at a mean age of 21 months. Secondary defect of mitochondrial fatty oxidation or respiratory chain was found in skeletal muscle of two patients. The intragenic deletion, c.2295-866&#95;2410-30del, was identified in 8/17 patients (47%), all Caucasians, and occurred on the background of a common haplotype, suggesting a founder effect. This deleted human LPIN1 form was unable to complement Delta pah1 yeast for growth on glycerol, in contrast to normal LPIN1. Since more than 50% of our series harboured LPIN1 mutations, LPIN1 should be regarded as a major cause of severe myoglobinuria in early childhood. The high frequency of the intragenic LPIN1 deletion should provide a valuable criterion for fast diagnosis, prior to muscle biopsy., ((c) 2010 Wiley-Liss, Inc.)

Introduction: The entrapment of the suprascapular nerve (SSN) is commonly considered at the level of the suprascapular notch and more rarely in the spinoglenoid notch. Recent per-operative findings showed a compression of the SSN along its course in the supraspinatus fossa. The removal of a fascia for releasing the nerve between the suprascapular notch and spinoglenoid notch led us to purchase an anatomical study., Materials and Methods: 30 cadaver shoulders have been dissected. The morphological features about the suprascapular notch, the supraspinatus fascia, and the spinoglenoid notch have been observed. Histological studies of the fascia and the spinoglenoid ligament have been performed. Morphometric parameters such as shape of the suprascapular notch, diameters of the SSN before and after the suprascapular notch, distance between the two notches, length of the course of the SSN into the supraspinatus fossa, diameters of the spinoglenoid notch have been measured., Results: The shape of the suprascapular notch could be seen as "U"- or "V" as previously reported. The fascia was quite constant (completely identified in 29 shoulders) and was the lateral extension of the supraspinatus fascia. The SSN coursed between the bone and the fascia and was surrounded by fat tissue. This fascia was thickened at the level of the spinoglenoid notch and joined the infraspinatus fascia. The spinoglenoid ligament was seen in 28 shoulders., Discussion and Conclusion: In pathologic and post-trauma conditions, the fascia can be retracted or thickened and the SSN may be entrapped along its course in the supraspinatus fossa, between the suprascapular notch and the spinoglenoid notch and without any compression in any notch. These anatomical data lead us to consider that a tunnel syndrome may concern the SSN.

Background: Cutaneous Bowen's disease (CBD) is a form of intraepithelial squamous cell carcinoma that usually presents as a solitary lesion. We report four similar cases of a peculiar and well-delimited clinical subset of multiple Bowen's disease seen in the lower limbs in elderly women and associated with specific therapeutic problems., Observations: Four women aged over 70 years presented with multiple CBD limited to the lower limbs associated with squamous cell and superficial basal cell carcinomas along with actinic keratosis. No significant aetiological factors were present apart from chronic sun exposure other than one case possibly involving immunodeficiency. The four patients were treated using photodynamic therapy, and partial clinical response and good tolerance were observed., Discussion: These four cases share numerous clinical similarities: elderly women, markers of chronic sun exposure, lack of other aetiological factors such as arsenic or irradiation, localization of the lesions (multiple and/or continuous layer pattern, restricted to the lower limbs in all cases) and a chronic course. The frequency of this subset is probably underestimated due to absence of biopsies or to inconclusive histology reports. Photodynamic therapy yields valuable results with a good efficacy/safety ratio compared to imiquimod or 5-fluorouracil. However, while this treatment could be considered a first-line option in multiple CBD, its therapeutic value requires more detailed evaluation.

Venous thromboses are rare in childhood. In the neonatal period, these are mainly neonatal renal venous thromboses (NRVT). We propose a synthesis of the main recent reviews on NRVT published over the last 15 years. These studies reported the higher male prevalence, the predominance of left kidney vein involvement, the increasing incidence in premature newborns, and a high level of thrombophilia in screened newborns. The usual presentation of NRVT, which associates abdominal mass, macroscopic hematuria, and thrombocytopenia, has been progressively modified by these new epidemiological features. The abdominal Doppler ultrasound scan is widely used for diagnosis and must be systematically associated with a transfontanellar ultrasound to look for cerebral hemorrhage, which should be a contraindication for anticoagulation. Recent consensus recommends at least prophylactic heparin therapy in the majority of cases to prevent thrombus extension. Fibrinolysis should be reserved for bilateral thrombosis with systemic effects. Despite improvements in screening and care, mean-term and long-term sequellae such as kidney atrophia, moderate renal insufficiency, systemic hypertension, and relapses in case of thrombophilia are still frequent and severe. A systematic follow-up by pediatric nephrologists is recommended.

Cardio-facio-cutaneous (CFC) syndrome, Noonan syndrome (NS), and Costello syndrome (CS) are clinically related developmental disorders that have been recently linked to mutations in the RAS/MEK/ERK signalling pathway. This study was a mutation analysis of the KRAS, BRAF, MEK1 and MEK2 genes in a total of 130 patients (40 patients with a clinical diagnosis of CFC, 20 patients without HRAS mutations from the French Costello family support group, and 70 patients with NS without PTPN11 or SOS1 mutations). BRAF mutations were found in 14/40 (35%) patients with CFC and 8/20 (40%) HRAS-negative patients with CS. KRAS mutations were found in 1/40 (2.5%) patients with CFC, 2/20 (10%) HRAS-negative patients with CS and 4/70 patients with NS (5.7%). MEK1 mutations were found in 4/40 patients with CFC (10%), 4/20 (20%) HRAS-negative patients with CS and 3/70 (4.3%) patients with NS, and MEK2 mutations in 4/40 (10%) patients with CFC. Analysis of the major phenotypic features suggests significant clinical overlap between CS and CFC. The phenotype associated with MEK mutations seems less severe, and is compatible with normal mental development. Features considered distinctive for CS were also found to be associated with BRAF or MEK mutations. Because of its particular cancer risk, the term "Costello syndrome" should only be used for patients with proven HRAS mutation. These results confirm that KRAS is a minor contributor to NS and show that MEK is involved in some cases of NS, demonstrating a phenotypic continuum between the clinical entities. Although some associated features appear to be characteristic of a specific gene, no simple rule exists to distinguish NS from CFC easily.

Chordoma is a rare bone tumor, believed to derive from notochordal rests, which generally arises at the two extremities of axial skeleton. We present a literature review on chordomas. Diagnosis has been greatly improved by MRI and immunohistochemistry. Conversely, complementary immunohistochemistry, cytometry and cytogenetic techniques have failed to improve prognosis evaluation. Radical surgery with free surgical margins is the most accurate curative treatment. Progress in radiotherapy should offer new therapeutic perspectives in the future. The recognition of new entities such as giant notochordal rest or hamartoma, and notochordal cells benign tumor, can lead to confusion since there is no consensus regarding their nature and whether or not they correspond to chordoma precursors. Prudence should be the rule in order to avoid overtreatment.

Thymomas are tumours that rarely occur in children, are almost invariably benign, and are usually discovered incidentally in the anterior mediastinum on chest X-rays. Whereas in adults these tumours are often associated with myasthenia gravis and other autoimmune diseases, this occurrence is very rare in the paediatric population. Multiple localisation and/or extra-thoracic recurrence of thymomas in children also appears to be exceptional with no reported cases in the English literature. We report one rare paediatric case.

Salts of N-trifluoromethylsulfonyl derivatives of trifluoromethyl- and phenylsulfonimidoyl imides have been synthesized by two different routes. Both methods are one-pot reactions, that run in mild conditions with good yields. Two novel organic super acids: bis[N-(trifluoromethylsulfonyl)trifluoromethanesulfonimidoyl]imide and N,N'-bis(trifluoromethyl-sulfonyl)diimino trifluoromethanesulfonic acid were prepared and the structure of their potassium salts was obtained by single-crystal X-ray diffraction.

Background: Capillary haemangioma of the central nervous system is extremely rare. Histologically proven cases developed in the dura mater and choroid plexus, or were typically intracranial extensions of an extra-cranial lesion., Features: This report details a case that developed in the anterior choroidal artery of a newborn infant and manifested as a lethal intra-cerebral haemorrhage. Pathological criteria for the diagnosis of vascular malformations should be carefully investigated and the differential diagnoses of the present case are discussed., Prognosis: Intracranial haemangioma presents a diagnostic challenge and the treatment of deep lesions remains problematic.

The different alleles at the (TG)m(T)n polymorphic loci at the 3' end of the human CFTR intron 8 determine the efficiency by which exon 9 is spliced. We identified a novel TG12T3 allele in a congenital bilateral absence of vas deferens (CBAVD) patient who carries a [TG11T7; p.Phe508Cys; p.Met470Val] haplotype on the other chromosome. To better understand the complex regulation of exon 9 splicing, we analyzed the levels of correctly spliced CFTR transcripts in six CFTR-expressing epithelial cell lines derived from lung, colon, testis, vas deferens, and epididymis transiently transfected with four CFTR minigenes (pTG11T7, pTG12T7, pTG12T5, and pTG12T3). In this work, we show that a decrease in the Ts at the polymorphic locus in a TG12 background determines a cell-type dependent reduction in exon 9+ transcripts that is not related to the basal splicing efficiency in the cell line. These data emphasize the role of the T5 allele in CBAVD and identify the T3 allele as a severe cystic fibrosis (CF) disease-causing mutation. Finally, UV cross-linking experiments demonstrated that tissue-specific trans-acting splicing factors do not contribute to the different patterns of exon 9 splicing found between the cell lines. However, we observed that lower numbers of Ts can alter the binding of TDP-43 (TDP43 or TARDBP) to its specific target ug12 in a tissue-specific manner. Our results support the idea that the ratio of general splicing factors plays a role in the tissue variability of exon 9 alternative splicing., ((c) 2004 Wiley-Liss, Inc.)

Introduction: Familial dyskeratotic comedones is a rare affection of autosomal transmission and characterized by pseudo-comedone papules predominantly on the limbs. We report a new familial case characterized by its clinical and histological profile., Case Report: A 6 year-old boy presented with a papular, pseudo-comedone eruption that had appeared shortly after birth and had progressively extended symmetrically to both legs. The child's father complained of a similar eruption since childhood. Histological examination of the papules revealed a pseudo-follicular invagination, obstructed by keratin and associated with areas of focal dyskeratosis. Treatment with local retinoids was ineffective., Discussion: Since it is often asymptomatic, the prevalence of dyskeratosis comedones is probably underestimated. A review of the literature on the preceding observations is presented. The dermatites that would represent differential diagnoses because of the presence of comedone-like lesions and/or histological dyskeratosis are discussed.

Bone vascular tumors are very rare. Epithelioid types are described according to their architecture, their degree of vascular differentiation, and their cytonuclear atypia. The include epithelioid hemangioma, epithelioid hemangioendothelioma, and angiosarcoma. We report a case of L4 corpus vertebral bone epithelioid hemangioma. The patient was a 25-year-old man with a tumor that recurred twice. The lesion was characterized by a vascular lumen lined by cells with regular nuclei and inflammatory infiltrates. Capillaries were lined by prominent epithelioid endothelial cells, associated with CD31+ and cytokeratin-.

Introduction: Simvastatin is a competitive inhibitor of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase which is effective in the treatment of various hyperlipidemia. We report a case of lichen planus pemphigoides induced by simvastatin treatment., Case Report: A 63-year-old man was treated for two months with simvastatin for hypercholesterolemia. One month later he developed a pruriginous and bullous lichenoid eruption. Histological and direct immunofluorescent features were consistent with the diagnosis of lichen planus pemphigoides. The Western blot analysis revealed antibodies directed against BP 180 kDa antigens. All the lesions progressively disappeared after treatment was discontinued., Discussion: Lichen planus pemphigoides may be due to the intake of drugs such as cinnarizine, captopril, ramipril and furosemide. Simvastatin may induce various drug eruptions such as pruritus, eczematous rash, cheilitis, angio-oedema and urticaria, porphyria cutanea tarda, lupus-like syndrome, dermatomyositis and lichenoid eruption. With the increasing use of HMG-CoA reductase inhibitors, an association between simvastatin and lichen planus pemphigoides should be kept in mind.

To distinguish between chondrosarcoma (grade 1--borderline histology) and enchondroma, we examined six chondrosarcomas (grade 1--borderline histology) which looked like benign lesions. Their diagnosis, albeit based on clinical, radiologic and pathologic examinations, was not easily reached. Moreover, we examined six enchondromas and 11 chondrosarcomas, the diagnoses of which were straightforward. All cartilaginous tumors were studied, placing emphasis on PAS-positive intracytoplasmic globules. Anti-Ki67 proliferation-associated nuclear antigen antibody and tenascin antibody were applied. The following features were observed in low-grade chondrosarcomas: (1) masses of hyalin and/or myxoid cartilage invading spaces around the tumor, (2) host lamellar bone trabeculae surrounded by cartilage on all sides, (3) tumoral resorption of bone trabeculae. Intracytopasmic hyalin globules (ICG) were more frequently found in malignant than in benign neoplasm (p = 0.042). Moreover, tenascin matrix immunoreactivity was more likely to be observed in benign than in malignant neoplasm (p = 0.029). Ki67 immunoreactivity was more frequent in characterized than in low-grade chondrosarcomas or in enchondromas, where it was null (p = 0.0044).

The synovial fold of the humeroradial joint is known, and sometimes considered as a meniscus that could be injured by chronic repeated trauma related to pronation and supination. The aims of this study were to determine the gross anatomy and histological structure of this fold, and to clarify its participation in the painful lateral syndromes of the elbow. Fifty elbows from adult cadavers were dissected. The capsule of the humeroradial part of the elbow joint was resected with the annular ligament. The presence of a synovial fold, and its location relative to the cranial edge of the annular ligament divided into five sectors (ventral, ventrolateral, lateral, laterodorsal and dorsal) were noted; morphological parameters such as thickness, width and length were measured. The histological examination determined the structure of the folds. Five synovial folds were resected during surgery for epicondylalgia in five patients who suffered from pain precisely at the level of the joint between the capitulum and the fovea radialis, and were also examined. A fold was present in 43 cases, and in two cases two folds were seen at the deep side of the junction between the capsule and the annular ligament. The most frequent positions were: dorsal ( n=11), laterodorsal and dorsal ( n=6;), lateral to dorsal ( n=5), lateral ( n=5), ventral ( n=4) and circular ( n=4). The mean length was 21.4 mm (range from 9-51 mm). The mean width was 2.9 mm (range 1-10 mm), and the mean maximal thickness 1.7 mm (range 1-4 mm). The histological study showed two types of folds: a rigid structure, with oriented fibrous tissue, triangular with a peripheral capsular base, covered on its two sides and along the free edge by a synovial layer; and a pliable structure, formed of two synovial layers that surrounded a thin fatty tissue, with a villous appearance of the free edge. No fibromyxoid structure, as in a real meniscus, was observed. Some nerve fibers were seen in the folds. The five folds resected in operated patients were hypertrophic, and showed an increased number of nerve fibers, along the capsule but also close to the synovial layer. Some painful syndromes of the lateral side of the elbow are not related to tendinitis or to posterior interosseous nerve compression, but have an intra-articular origin. This study showed that the synovial fold is not a meniscus, and may be involved in the etiology of lateral epicondylalgia.

Unlabelled: Chronic recurrent multifocal osteomyelitis (CRMO) is a disorder rarely localized to the lower jaw., Case Report: A fourteen-year-old boy complained of a swollen of his lower jaw. After a CT Scan, a bone biopsy was performed and yielded S. oralis against which an adapted intravenous antibiotherapy was administered without efficacy. The absence of malignant process and the revelation of an other focus of fixation at the Tc bone scan localized on humerus called to mind the diagnosis of CRMO., Conclusion: The diagnosis of this disease is difficult and based on a number of concording arguments:clinical and radiological signs of osteomyelitis, multifocal presentation, recurrent relapses and remissions, inaction of antibiotics, elimination of the other differential diagnosis, in particular the infectious osteitis.

Propionibacterium acnes is an anaerobic bacillus implicated in certain chronic arthritides. This report describes an HLA-B27+ 17-year-old woman with acne vulgaris who presented with rapidly destructive arthritis in the left shoulder as well as an evolving left subclavicular adenopathy. One year later, arthritis was detected in the left knee; the inflammatory synovial fluid was sterile. Growth of P acnes was observed in cultures of the shoulder synovium and lymph nodes, but polymerase chain reaction was negative for Borrelia, Chlamydia, and Ureaplasma DNA. Three months of treatment with amoxicillin and rifampicin led to clinical disappearance of the oligoarthritis, but arthritis recurred in the left knee after discontinuation of therapy. On biopsy, bacteria were undetectable in the knee synovium, but chronic arthritis was evident histologically. Antibiotics were reintroduced for 12 months and were again effective against the clinical symptoms. Although the asymmetry, histologic features, arthritis-acne association, and genetic predisposition of this chronic destructive oligoarthritis would seem to indicate a reactive arthropathy, the isolation of P acnes from 2 distinct specimens prompted us to propose calling this a case of septic-reactive arthritis, which is further supported by the absence of progression after antibiotic therapy and the persistence of the rheumatism. To our knowledge, this is the first demonstration of the efficacy of prolonged antibiotic therapy on the joint manifestations of chronic rheumatism associated with acne.

Objective: To retrospectively assess, with a sufficiently long followup (mean 11.6 years; median 9 years), the long-term outcome of chronic recurrent multifocal osteitis (CRMO), a multifocal, inflammatory bone disease., Methods: Patients included were 8 children/adolescents and 7 adults with no family history of rheumatic disease who had been diagnosed as having CRMO between 1979 and 1995. Ten patients had undergone at least 1 bone biopsy of the lesions, with histologic examination and multiple cultures. In 1996, in addition to an in-depth interview, 12 patients underwent an extensive physical examination, laboratory evaluation, HLA-A, B, C, and DR typing, bone radiography and scintigraphy, and computed tomography scan of the sternoclavicular and sacroiliac joints., Results: Remission was observed in 3 patients. The other 12 patients developed various associations of vertebral (n = 10), sacroiliac (n = 6), anterior thoracic (n = 7), peripheral articular (n = 2), enthesopathic (n = 4), or dermatologic (palmoplantar pustulosis in 3 cases and psoriasis in 2) involvements. Spine involvement was the most common and occurred the earliest (median time to appearance after the onset of osteitis 5.63 years). Clinical sacroiliitis was always unilateral. No patients carried the HLA-B27 haplotype. CRMO responded well to nonsteroidal antiinflammatory drugs. Twelve patients met the European Spondylarthropathy Study Group criteria for spondylarthopathy., Conclusion: After 10 years, CRMO had usually evolved to spondylarthropathy, but with certain features not usually seen in the latter: predominantly, unilateral sacroiliitis, no familial form, and no link with HLA-B27.

Jaffe-Campanacci syndrome is a rare entity characterized by disseminated non ossifying fibromas in association with extraskeletal congenital anomalies: cutaneous, genital, ocular and cardiovascular. Mental retardation is also frequently observed. Pathological fractures are the usual mode of revelation. We report one case original because of causal discovery during orthodontic check-up and because of extraskeletal anomalies not previously described. In fact the true incidence of this syndrome is probably underestimated because of unrecognized features.

Objectives: Because osteoclastic bone resorption is stimulated in multiple myeloma, we evaluated the efficacy of etidronate in this disease, in a multicentre controlled study., Methods: Ninety-four previously untreated patients with stage II or III multiple myeloma received, in addition to the same chemotherapy, 10 mg/kg/day etidronate per os (n = 49) or placebo (n = 45) for 4 months. The evaluation was clinical (pain, Karnofsky, survival), biological and radiological. Forty-one patients had iliac bone biopsy before the treatment and 34 patients also at the end of the study. Histologic bone parameters were compared with 49 normal controls., Results: No statistical difference was found between etidronate and placebo treated patients for clinical, biological and radiological parameters. Compared with controls, pretreatment biopsies showed markedly increased bone resorption and decreased trabecular bone volume. Bone resorption decreased significantly in patients with etidronate compared with those with placebo (p < 0.05)., Conclusion: Though we found no clinical, biological and radiological difference with placebo, etidronate inhibited the increased bone resorption in multiple myeloma.

Karyotypic analysis of a clear cell sarcoma revealed a translocation t(12;22) (q13-14;q12) as a primary chromosomal change. This case is the third clear cell sarcoma cytogenetically analyzed; the two previously reported cases had t(12;22)(p11;p11), and a complex karyotype with trisomy 22, respectively.