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Introduction: Vitamin D--dependent rickets type 1A (VDDR1A) is a rare genetic disease associated with loss-of-function variations in the gene encoding the vitamin D--activating enzyme 1α-hydroxylase (CYP27B1). Phenotype-genotype correlation is unclear. Long-term outcome data are lacking. The objective of this study was to describe characteristics and outcomes to search for a phenotype-genotype correlation. Methods: We retrospectively collected clinical data, genetic features, and outcomes from 24 genetically confirmed cases from 10 French centers; results are presented as median (min--max). Results: Clinical symptoms at diagnosis (age, 1.5 [0.5-8.7] years) were mainly bone and neurological abnormalities, and laboratory data showed hypocalcemia (1.97 [1.40-2.40] mmol/L), hypophosphatemia (-3.4 [-13.4 to (-)0.2] SD score for age), low 25OHD and low 1,25(OH)2D3, secondary hyperparathyroidism with PTH at 6.6 (1.3-13.7) times the upper limit for normal (ULN; PTH expressed as ULN to homogenize data presentation), and increased alkaline phosphatase (1968 [521-7000] IU/L). Bone radiographs were abnormal in 83% of patients. We identified 17 variations (11 missense, 3 frameshift, 2 truncating, and 1 acceptor splice site variations) in 19 families (homozygous state in 58% [11/19]). The partial loss-of-function variation p.(Ala129Thr) was associated with a milder phenotype: older age at diagnosis, higher serum calcium (2.26 vs 1.85 mmol/L), lower PTH (4.7 vs 7.5 ULN), and lower alkaline phosphatase (759 vs 2082 IU/L). Patients were treated with alfacalcidol. Clinical (skeletal, neurological), biochemical, and radiological outcomes were satisfactory, and complications occurred if there was bad adherence. Conclusion: Overall, our findings highlight good outcomes under substitutive treatment and the need of a closer follow-up of eyes, teeth, kidneys, and blood pressure in VDDR1A. [ABSTRACT FROM AUTHOR]

Background Pseudohypoparathyroidism (PHP, OMIM #103580) is a very rare disease (incidence 0.3–1/100,000). Heterozygous inactivating mutations involving the maternal GNAS exons 1–13 that encodes the alpha subunit of the stimulatory G protein (Gsα) cause inactivating parathyroid hormone (PTH)/PTHrP signalling disorder type 2 (iPPSD2 or PHP type 1A), which is characterized by Albright hereditary osteodystrophy and resistance to multiple hormones that act through the Gsα signalling pathway (including PTH, thyroid-stimulating hormone, and α-melanocyte-stimulating hormone). To date, little information is available on craniofacial features in patients with PHP. The small number of patients studied in previous reports as well as the lack of molecular characterization of the patients may have precluded the detection of specific orofacial manifestations in the different PHP subtypes. Materials/Methods We conducted a systematic analysis of dental and craniofacial features in 19 patients with iPPSD2 and maternal GNAS inactivating mutations to assess the frequency and specificity of the anomalies. Results Facial examinations showed reduced vertical, sagittal, and transverse development of the mid-facial structures. Intraoral and radiographic examinations revealed that 89 per cent of the patients had at least one dental anomaly, including tooth submergence leading to severe infraocclusion in 83 per cent of cases. Craniofacial analysis of lateral cephalometric radiographs also showed a significant alteration in the development of the cranial base and maxillary and mandibular structures in these patients. Conclusions Patients with iPPSD2 and maternal GNAS mutations had specific craniofacial alterations and dental abnormalities. These specific defects should be assessed in order to provide appropriate dental and orthodontic care to these patients. (clinical trial registration: 1920371 v 0, French Nationale Data Processing and Liberties Commission - CNIL). [ABSTRACT FROM AUTHOR]

Background: The incidence of childhood type 1 diabetes (T1D) incidence is rising in many countries, supposedly because of changing environmental factors, which are yet largely unknown. The purpose of the study was to unravel environmental markers associated with T1D.Methods: Cases were children with T1D from the French Isis-Diab cohort. Controls were schoolmates or friends of the patients. Parents were asked to fill a 845-item questionnaire investigating the child's environment before diagnosis. The analysis took into account the matching between cases and controls. A second analysis used propensity score methods.Results: We found a negative association of several lifestyle variables, gastroenteritis episodes, dental hygiene, hazelnut cocoa spread consumption, wasp and bee stings with T1D, consumption of vegetables from a farm and death of a pet by old age.Conclusions: The found statistical association of new environmental markers with T1D calls for replication in other cohorts and investigation of new environmental areas.Trial Registration: Clinical-Trial.gov NCT02212522 . Registered August 6, 2014. [ABSTRACT FROM AUTHOR]

Background: Pseudohypoparathyroidism (PHP, OMIM #103580) is a very rare disease (incidence 0.3-1/100,000). Heterozygous inactivating mutations involving the maternal GNAS exons 1-13 that encodes the alpha subunit of the stimulatory G protein (Gsα) cause inactivating parathyroid hormone (PTH)/PTHrP signalling disorder type 2 (iPPSD2 or PHP type 1A), which is characterized by Albright hereditary osteodystrophy and resistance to multiple hormones that act through the Gsα signalling pathway (including PTH, thyroid-stimulating hormone, and α-melanocyte-stimulating hormone). To date, little information is available on craniofacial features in patients with PHP. The small number of patients studied in previous reports as well as the lack of molecular characterization of the patients may have precluded the detection of specific orofacial manifestations in the different PHP subtypes., Materials/methods: We conducted a systematic analysis of dental and craniofacial features in 19 patients with iPPSD2 and maternal GNAS inactivating mutations to assess the frequency and specificity of the anomalies., Results: Facial examinations showed reduced vertical, sagittal, and transverse development of the mid-facial structures. Intraoral and radiographic examinations revealed that 89 per cent of the patients had at least one dental anomaly, including tooth submergence leading to severe infraocclusion in 83 per cent of cases. Craniofacial analysis of lateral cephalometric radiographs also showed a significant alteration in the development of the cranial base and maxillary and mandibular structures in these patients., Conclusions: Patients with iPPSD2 and maternal GNAS mutations had specific craniofacial alterations and dental abnormalities. These specific defects should be assessed in order to provide appropriate dental and orthodontic care to these patients. (clinical trial registration: 1920371 v 0, French Nationale Data Processing and Liberties Commission - CNIL)., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)