ABSTRACT
INTRODUCTION: Tonne-Kalscheuer syndrome (TOKAS) is a recessive X-linked multiple congenital anomaly disorder caused by RLIM variations. Of the 41 patients reported, only 7 antenatal cases were described. METHOD: After the antenatal diagnosis of TOKAS by exome analysis in a family followed for over 35 years because of multiple congenital anomalies in five male fetuses, a call for collaboration was made, resulting in a cohort of 11 previously unpublished cases. RESULTS: We present a TOKAS antenatal cohort, describing 11 new cases in 6 French families. We report a high frequency of diaphragmatic hernia (9 of 11), differences in sex development (10 of 11) and various visceral malformations. We report some recurrent dysmorphic features, but also pontocerebellar hypoplasia, pre-auricular skin tags and olfactory bulb abnormalities previously unreported in the literature. Although no clear genotype-phenotype correlation has yet emerged, we show that a recurrent p.(Arg611Cys) variant accounts for 66% of fetal TOKAS cases. We also report two new likely pathogenic variants in RLIM, outside of the two previously known mutational hotspots. CONCLUSION: Overall, we present the first fetal cohort of TOKAS, describe the clinical features that made it a recognisable syndrome at fetopathological examination, and extend the phenotypical spectrum and the known genotype of this rare disorder.
ABSTRACT
OBJECTIVES: To evaluate the reliability of the OMERACT paediatric ultrasound (US) synovitis definitions and scoring system in JIA. METHODS: Thirteen sonographers analysed 75 images for the presence/absence of elementary lesions (binary scoring) and for grading synovitis, synovial hypertrophy, effusion and Doppler signals. Static US images of the second metacarpophalangeal joint (MCP-II), wrist, elbow, knee and ankle in JIA patients at different ages and different disease stages were collected with standardized scanning by two experienced sonographers. Intra- and inter-reader reliability were analysed with kappa coefficients. RESULTS: Intra-reader reliability was good for binary scoring (Cohen's kappa 0.62, range 0.47-0.75), synovitis and synovial hypertrophy; excellent for Doppler signals (quadratic weighted kappa 0.77, 0.66-0.86; 0.76, 0.61-0.84; and 0.87, 0.77-0.94, respectively); and moderate for effusion (0.55, 0.24-0.76). Inter-reader reliability was good for synovitis and synovial hypertrophy (Light's kappa 0.68, 95% CI: 0.61, 0.75 and 0.63, 0.54-0.71, respectively), excellent for Doppler signals (0.85, 95% CI: 0.77, 0.90), and moderate for binary scoring and effusion (0.48, 95% CI: 0.36, 0.64 and 0.49, 0.40-0.60, respectively). We obtained the best scores for the knee (0.71, 0.54-0.85) except for Doppler signals, with reliability higher for MCP-II. We found a trend toward better results in older children. CONCLUSIONS: This is the first study establishing the reliability of the OMERACT paediatric US synovitis definitions and scoring system in the five most commonly affected joints in JIA. The reliability was good among a large group of sonographers. These results support the applicability of these definitions and scoring system in clinical practice and multicentre studies.
Subject(s)
Arthritis, Juvenile/diagnostic imaging , Joints/diagnostic imaging , Synovitis/diagnostic imaging , Ultrasonography/methods , Humans , Reproducibility of Results , Severity of Illness IndexABSTRACT
Mutations in the CHRNG gene cause autosomal recessive multiple pterygium syndrome (MPS). Herein we present a long-term follow-up of seven patients with CHRNG-related nonlethal MPS and we compare them with the 57 previously published patients. The objective is defining not only the clinical, histopathological, and molecular genetic characteristics, but also the type and degree of muscle involvement on whole-body magnetic resonance imaging (WBMRI). CHRNG mutations lead to a distinctive phenotype characterized by multiple congenital contractures, pterygium, and facial dysmorphism, with a stable clinical course over the years. Postnatal abnormalities at the neuromuscular junction were observed in the muscle biopsy of these patients. WBMRI showed distinctive features different from other arthrogryposis multiple congenita. A marked muscle bulk reduction is the predominant finding, mostly affecting the spinal erector muscles and gluteus maximus. Fatty infiltration was only observed in deep paravertebral muscles and distal lower limbs. Mutations in CHRNG are mainly located at the extracellular domain of the protein. Our study contributes to further define the phenotypic spectrum of CHRNG-related nonlethal MPS, including muscle imaging features, which may be useful in distinguishing it from other diffuse arthrogryposis entities.
Subject(s)
Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/genetics , Genetic Association Studies , Genetic Predisposition to Disease , Malignant Hyperthermia/diagnosis , Malignant Hyperthermia/genetics , Mutation , Phenotype , Receptors, Nicotinic/genetics , Skin Abnormalities/diagnosis , Skin Abnormalities/genetics , Abnormalities, Multiple/therapy , Adolescent , Alleles , Amino Acid Substitution , Biopsy , Child, Preschool , Echocardiography , Female , Genetic Association Studies/methods , Genetic Testing , Genotype , Humans , Magnetic Resonance Imaging , Male , Malignant Hyperthermia/therapy , Models, Molecular , Muscle, Skeletal/diagnostic imaging , Muscle, Skeletal/pathology , Protein Conformation , Receptors, Nicotinic/chemistry , Skin Abnormalities/therapy , Structure-Activity Relationship , Whole Body ImagingABSTRACT
The cutis laxa syndromes are multisystem disorders that share loose redundant inelastic and wrinkled skin as a common hallmark clinical feature. The underlying molecular defects are heterogeneous and 13 different genes have been involved until now, all of them being implicated in elastic fiber assembly. We provide here molecular and clinical characterization of three unrelated patients with a very rare phenotype associating cutis laxa, facial dysmorphism, severe growth retardation, hyperostotic skeletal dysplasia, and intellectual disability. This disorder called Lenz-Majewski syndrome (LMS) is associated with gain of function mutations in PTDSS1, encoding an enzyme involved in phospholipid biosynthesis. This report illustrates that LMS is an unequivocal cutis laxa syndrome and expands the clinical and molecular spectrum of this group of disorders. In the neonatal period, brachydactyly and facial dysmorphism are two early distinctive signs, later followed by intellectual disability and hyperostotic skeletal dysplasia with severe dwarfism allowing differentiation of this condition from other cutis laxa phenotypes. Further studies are needed to understand the link between PTDSS1 and extra cellular matrix assembly.
Subject(s)
Cutis Laxa/diagnosis , Cutis Laxa/genetics , Hyperostosis/diagnosis , Hyperostosis/genetics , Mutation , Nitrogenous Group Transferases/genetics , Phenotype , Adult , Alleles , Child , Child, Preschool , Exons , Facies , Female , Genetic Association Studies , Genotype , Humans , Male , RadiographyABSTRACT
OBJECTIVE: The aim of this retrospective study was to perform magnetic resonance imaging assessment of olfactory pathway and skull base abnormalities in Kallmann syndrome (KS) patients with hypogonadotropic hypogonadism and olfaction disorder. METHODS: Magnetic resonance brain patterns were retrospectively studied in 19 patients clinically classified as KS. Qualitative assessment of olfactory bulb region comprised bulb atrophy and rectus and medial orbital gyrus ptosis; quantitative assessment measured olfactory fossa depth and width, sulcus depth and ethmoid angle. Results were compared to an age- and sex-matched control population (n=19) with no impairment in the region of interest. Sixteen of the 19 KS patients were genetically screened for mutations associated with KS. RESULTS: On the above qualitative criteria, 15 of the 19 patients presented either unilateral (n=2) or bilateral (n=13) olfactory bulb agenesis; 16 showed tract agenesis and 16 showed gyrus malformation (ptosis or absence). On the quantitative criteria, 18 of the 19 patients showed abnormal sulcus depth and/or olfactory fossa malformation and/or abnormal ethmoid angle. CONCLUSION: The presence of malformation abnormalities in the olfactory fossae of 18 of the 19 patients appears to be a key factor for etiological diagnosis of hypogonadotropic hypogonadism, and should enable targeted study of genes involved in KS.
Subject(s)
Kallmann Syndrome/diagnostic imaging , Magnetic Resonance Imaging/methods , Olfactory Bulb/abnormalities , Olfactory Bulb/diagnostic imaging , Adolescent , Adult , Female , Humans , Hypogonadism/diagnostic imaging , Kallmann Syndrome/genetics , Male , Middle Aged , Olfaction Disorders/diagnostic imaging , Olfactory Cortex/abnormalities , Olfactory Cortex/diagnostic imaging , Olfactory Pathways/abnormalities , Olfactory Pathways/diagnostic imaging , Retrospective Studies , Young AdultABSTRACT
Rasmussen encephalitis (RE) is a severe epileptic and inflammatory encephalopathy of unknown etiology, responsible for focal neurological signs and cognitive decline. The current leading hypothesis suggests a sequence of immune reactions induced by an indeterminate factor. This sequence is thought to be responsible for the production of autoantibody-mediated central nervous system degeneration. However, these autoantibodies are not specific to the disease and not all patients present with them. We report the case of a 4-year-old girl suffering from RE displaying some atypical features such as fast evolution and seizures of left parietal onset refractory to several antiepileptics, intravenous immunoglobulins, and corticosteroids. Serum autoantibodies directed against voltage-gated potassium channels (VGKC) were evidenced at 739 pM, a finding never previously reported in children. This screening was performed because of an increased signal in the temporolimbic areas on brain magnetic resonance imaging, which was similar to what is observed during limbic encephalitis. The patient experienced epilepsia partialis continua with progressive right hemiplegia and aphasia. She underwent left hemispherotomy at the age of 5.5 years after which she became seizure free with great cognitive improvement. First described in adults, VGKC autoantibodies have been recently described in children with various neurological manifestations. The implication of VGKC autoantibodies in RE is a new observation and opens up new physiopathological and therapeutic avenues of investigation.
Subject(s)
Autoantibodies/blood , Encephalitis/blood , Potassium Channels, Voltage-Gated/immunology , Brain/pathology , Brain/physiopathology , Child, Preschool , Electroencephalography , Encephalitis/diagnosis , Female , Humans , Magnetic Resonance ImagingABSTRACT
An atypical teratoid/rhabdoid tumor of the central nervous system is an aggressive infantile embryonal neoplasm, usually presenting as an infratentorial and intraparenchymatous lesion. We report on magnetic resonance imaging findings of a 22-month-old boy with a biopsy-proven primary rhabdoid tumor, presenting as a single intracranial supratentorial extra-axial mass. Based on the patient's age and imaging features (perfusion, diffusion magnetic resonance imaging, and magnetic resonance spectroscopy), a diagnosis of atypical teratoid/rhabdoid tumor was more accurate than diagnoses of meningioma and primitive neuroectodermal tumor. Although this entity is relatively rare, it should be considered in the differential diagnosis of dural-based, space-occupying central nervous system lesions.
Subject(s)
Brain Neoplasms/diagnosis , Brain Neoplasms/pathology , Rhabdoid Tumor/diagnosis , Rhabdoid Tumor/pathology , Supratentorial Neoplasms/diagnosis , Supratentorial Neoplasms/pathology , Brain/metabolism , Brain/pathology , Brain/surgery , Brain Edema/pathology , Brain Neoplasms/therapy , Diagnosis, Differential , Diffusion Magnetic Resonance Imaging , Humans , Infant , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Male , Neoplasm Recurrence, Local , Rhabdoid Tumor/therapy , Supratentorial Neoplasms/therapy , Treatment OutcomeABSTRACT
BACKGROUND: Achondroplasia is one of the most common forms of short limb dwarfism. It is usually suspected on third trimester routine ultrasound because of very shortened long bones. We have described two new prenatal sonographic signs of achondroplasia visible at the proximal femoral metaphysis. METHODS: Over 5 years, five fetuses were diagnosed with achondroplasia at the Grenoble Prenatal Diagnosis Centre. Ultrasound and tomographic examinations were performed by specialists. To study the proximal metaphysis, the ultrasound transducer was positioned at a 45 degree angle to the diaphyseal axis. Postnatal diagnosis was confirmed. RESULTS: On computed tomography and postnatal X-ray, proximal femoral metaphysis appeared rounded, with poor, uneven ossification. Connexion to diaphysis was abnormal, with relative overgrowth of the periosteum, creating a new diagnostic sign that we called the 'collar hoop' sign. On ultrasound, all fetuses had a very rounded metaphyseal-epiphyseal interface, with an angle connexion to diaphysis wider than expected. The 'collar hoop' sign was obvious on four of the fetuses. During the same period, proximal femoral metaphyses appeared normal in 653 healthy fetuses, suggesting high specificity of those two new signs. CONCLUSION: Metaphysis examination is recommended if fetal femur length measures below the fifth percentile, as normal aspect may rule out achondroplasia.
Subject(s)
Achondroplasia/diagnostic imaging , Ultrasonography, Prenatal , Female , Femur/diagnostic imaging , Femur/growth & development , Hip Joint/diagnostic imaging , Humans , Infant, Newborn , Organ Size , Pregnancy , Tomography, X-Ray ComputedABSTRACT
Polyorchidism is an urogenital curiosity defined by the presence of more than two testes confirmed by histology. This anomaly is extremely rare and only a hundred world cases were described in the literature. Although it can remain asymptomatic, polyorchidism is often associated to processus vaginalis anomalies in childhood (hernia, hydrocele) and undescended testis. The review of the literature finds cases of polyorchidism revealed by testis torsion and an increased risk of malignancy and infertility. We report the case of polyorchidism in a 14 year old child, at whom a painful testis mass indicate surgical exploration and documented the histological diagnosis of polyorchidism. Through this observation and review of the literature, authors describe pathological and managment findings of polyorchidism.
Subject(s)
Testis/abnormalities , Adolescent , Humans , Male , Testis/diagnostic imaging , Testis/surgery , UltrasonographyABSTRACT
The putative role of aluminium intake in young Bangladeshi children (1.5 to 4 years of age) with calcium-deficient rickets was evaluated in a non randomised controlled eight month trial. The effects of aluminium or stainless-steel cooking pots on bone metabolism were assessed by measuring blood calcium, phosphorus, alkaline phosphatase, parathyroid hormone, 1,25 dihydroxy vitamin D, aminoterminal propeptide of type 1 collagen (PINP), cross-linked carboxyterminal telopeptide of type 1 collagen (ICTP), aluminium and albumin, and by analysis of wrist radiographs. In both groups, blood alkaline phosphatase, 1,25 dihydroxy vitamin D and aluminium decreased significantly, white serum albumin increased (p < 0.01). These results suggest that the nutrition may well be of major importance, whereas the role of aluminium appears to be insignificant.