ABSTRACT
CONTEXT: Heterozygous GNAS inactivating mutations are known to induce pseudohypoparathyroidism type 1a when maternally inherited and pseudopseudohypoparathyroidism when paternally inherited. Progressive osseous heteroplasia (POH) is a rare disease of ectopic bone formation, and studies in different families have shown that POH is also caused by paternally inherited GNAS mutations. OBJECTIVE: Our purpose was to characterize parental origin of the mutated allele in de novo cases of POH and to draw phenotype/genotype correlations according to maternal or paternal transmission of a same GNAS mutation. DESIGN AND SETTING: We conducted a retrospective study on patients addressed to our referral center for the rare diseases of calcium and phosphorus metabolism. PATIENTS AND METHODS: We matched 10 cases of POH with cases of pseudohypoparathyroidism type 1a carrying the same GNAS mutations. MAIN OUTCOME MEASURES: The parental origin of the mutated allele was studied using informative intragenic polymorphisms and subcloning of PCR products. RESULTS: Paternal origin of GNAS mutations was clearly demonstrated in eight POH cases including one patient with mutation in exon 1. Genotype/phenotype analyses suggest that there is no direct correlation between the ossifying process and the position of the inactivating GNAS mutation. It is, however, more severe in patients in whom origin of the mutation is paternal. Severe intrauterine growth retardation was clearly evidenced in paternally inherited mutations. CONCLUSIONS: Clinical heterogeneity makes genetic counseling a delicate matter, especially in which paternal inheritance is concerned because it can lead to either a mild expression of pseudopseudohypoparathyroidism or a severe expression of POH.
Subject(s)
Bone and Bones , Choristoma/genetics , Choristoma/pathology , GTP-Binding Protein alpha Subunits, Gs/genetics , Mutation/genetics , Mutation/physiology , Child , Child, Preschool , Chromogranins , DNA Methylation , Databases, Genetic , Female , Genomic Imprinting , Genotype , Humans , Infant , Male , Parathyroid Hormone/physiology , Pedigree , Polymorphism, Single Nucleotide , Pseudohypoparathyroidism/genetics , Pseudopseudohypoparathyroidism/genetics , RNA/geneticsABSTRACT
Used for more than 10 years in addition to physiotherapy, orthopaedic surgery and rehabilitation, biphosphonate therapy has transformed the management of children with severe or moderate form of osteogenesis imperfecta. The authors of this article report indications, administration's way, duration and safety of biphosphonate therapy with uncertainties about persistence in skeleton for many years.
Subject(s)
Bone Density Conservation Agents/therapeutic use , Diphosphonates/therapeutic use , Osteogenesis Imperfecta/drug therapy , Absorptiometry, Photon , Administration, Oral , Bone Density/drug effects , Bone Density Conservation Agents/adverse effects , Child , Child, Preschool , Combined Modality Therapy , Diphosphonates/adverse effects , Dose-Response Relationship, Drug , Drug Administration Schedule , Fracture Healing/drug effects , Humans , Infant , Infusions, Intravenous , Long-Term Care , Pamidronate , Physical Therapy ModalitiesSubject(s)
Medicine , Pain Management , Specialization , Adolescent , Child , Chronic Disease , Humans , Pain/physiopathology , Pain/psychology , RecurrenceABSTRACT
We report the results of the cross-cultural adaptation and validation into the French language of two health status instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health related quality of life instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. Five hundred children were enrolled including 306 patients with JIA classified into systemic (23%), polyarticular (22%), extended oligoarticular (25%), and persistent oligoarticular (30%) subtypes, and 194 healthy children. Both instruments were reliable with intra-class correlation (ICC) coefficients for the test-retest procedure of 0.91 for the CHAQ, and 0.87 and 0.89 for the physical and psychosocial summary scores of CHQ, respectively. Agreement between parents and children evaluated for the CHAQ was high with an ICC of 0.89 for the disability index; weighted kappa coefficients for the 8 domains ranged from 0.61 to 0.72. Convergent validity was demonstrated by significant correlations with the JIA core set of variables (physician and parent global assessment, scores for active joints and joints with limited range of motion, erythrocyte sedimentation rate) for both instruments. Both CHAQ and CHQ discriminated between healthy and JIA children, but only the disease specific CHAQ questionnaire discriminated clearly between the 4 JIA subtypes. In conclusion, the French versions of the CHAQ and the CHQ are reliable, and valid health assessment questionnaires to be used in children suffering from JIA.
Subject(s)
Arthritis, Juvenile/diagnosis , Cross-Cultural Comparison , Health Status , Surveys and Questionnaires , Adolescent , Child , Cultural Characteristics , Disability Evaluation , Female , France , Humans , Language , Male , Psychometrics , Quality of Life , Reproducibility of ResultsABSTRACT
The authors report on a case of cardiomyopathy with congestive heart failure in an infant with severe hypocalcemia related to vitamin D deficient rickets. The heart failure was successfully treated with calcium gluconate and vitamin D, associated with dobutamide.
Subject(s)
Cardiomyopathies/etiology , Hypocalcemia/etiology , Rickets/complications , Vitamin D Deficiency/complications , Calcium Gluconate/therapeutic use , Cardiomyopathies/drug therapy , Electrocardiography , Ergocalciferols/therapeutic use , Humans , Hypocalcemia/drug therapy , Infant , Male , Vitamin D Deficiency/drug therapyABSTRACT
The authors report on an 8-year-old girl who experienced bilateral subdural frontoparietal and interhemispheric empyema following sinusitis. The child improved after initial treatment with a 3 weeks course of parenteral antibiotics. Surgical drainage was further required because of clinical aggravation; however, this evolution was related to bilateral frontoparietal brain edema and abscesses fluid was sterile.
