Determinants and risk factors for renal damage: where do patients hospitalized for severe anorexia nervosa stand? A multi-center study.

BACKGROUND: Although renal damage is increasingly reported among the most undernourished patients with Anorexia Nervosa (AN), it remains underestimated in current practice, and often associated with acute dehydration. The purpose of our study was to evaluate the frequency, the extent, and the risk factors of renal involvement among adolescents and adults hospitalized in specialized units for AN. METHODS: In this multi-center study, 197 consecutive participants were included, aged 13-65, from 11 inpatient eating disorder psychiatric units. Information on the course of AN, clinical characteristics, biological data, and medication were collected. RESULTS: At admission, mean BMI was 13.1 (± 1.6) kg/m2 for a mean age of 20.74 (± 6.5) years and the z-score was - 3.6 (± 1.33). Six participants (3.0%) had hyponatremia, four (2.0%) had hypokalemia, and nine (4.5%) had hypochloremia. The Blood Urea Nitrogen/Creatinine ratio was over 20 for 21 (10.6%) participants. The mean plasma creatinine was 65.22 (± 12.8) µmol/L, and the mean eGFR was 74.74 (± 18.9) ml/min. Thirty- five participants (17.8%) had an eGFR > 90 ml/min, 123 (62.4%) from 60 to 90 ml/min, 35 (17.8%) from 45 to 60 ml/min, and 4 (2%) under 45 ml/min. In multivariate analysis, only BMI on admission was a determinant of renal impairment. The lower the BMI the more severe was the renal impairment. CONCLUSION: When eGFR is calculated, it highlights renal dysfunction found in severe AN requiring hospitalisation in specialized units. The severity of undernutrition is an independent associated factor. Kidney functionality tests using eGFR, in addition to creatinine alone, should be part of routine care for patients with AN to detect underlying renal dysfunction.

AN is a psychiatric illness with organic repercussions that are not always visible nor frequently investigated. Renal damage, if detected, is often attributed to dehydration, and is thought to be rapidly reversible. Assessment of its severity and evolution is therefore not systematic, even in eating disorder units specialised in the care of patients with AN. Our study explored the assessment of renal impairment among adolescents and adults hospitalized in psychiatric units using eGFR calculation. Our results showed that fewer than 18% of the patients hospitalized had normal renal function and that among the various criteria, only BMI on admission was related to the extent of this impairment. Assessment of renal function by eGFR calculation and not only by creatinine measures should be performed routinely in all situations requiring hospitalization in anorexia nervosa, regardless of the reason for hospitalization.

Hormonal Contraception Effects on Pulmonary Function in Adolescents with Cystic Fibrosis.

STUDY OBJECTIVE: Estrogens are suspected to have a negative effect on pulmonary function in women with cystic fibrosis (CF). The aim of our study was to investigate, in a CF adolescent population, the effect of hormonal contraception (HC) on lung function by assessing the forced expiratory volume in 1 second (FEV1), the number of exacerbations of pulmonary condition, and antibiotic use. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: We conducted a cohort retrospective chart review of girls from age 13 to 18 years old who were followed in the CF clinic of a university hospital center. Wilcoxon rank sum test with continuity correction, 2-sample t test, conditional test of Poisson rates, and χ2 test were conducted to identify differences in results between adolescents with or without use of HC for the following outcomes: FEV1, use of antibiotics by nebulizer, and hospital admission for exacerbations of pulmonary condition. RESULTS: Among 127 adolescents, 64/127 (50.4%) took HC; 12/127 (9%) continuously had been taking HC over 3 years. For girls taking HC for more than 3 years, FEV1 at 18 years old was significantly higher than for girls who had never taken HC (85.17% vs 71.05%; P = .043). However, there was no difference in the number of hospital admissions for exacerbation of pulmonary condition between these 2 groups (P = .057). There was no difference between HC vs non-HC users in the percent of patients taking antibiotics by nebulizer over the 6 years of follow-up. CONCLUSION: Our study suggests that in adolescents with CF, HC has no deleterious effects on the FEV1. Further prospective studies could be done to confirm these results.

In malnourished adolescent with anorexia nervosa, Cockroft-Gault formula is the most relevant formula to estimate renal function.

AIM: Serum creatinine level is the most used test to evaluate renal function in patients with anorexia nervosa (AN). We investigated which formula of glomerular filtration rate (GFR) based on simple blood sample had the best correlation with the gold standard in malnourished adolescent patients with AN. METHODS: A prospective study was conducted on 34 adolescents hospitalized for the restrictive type of AN between 2014 and 2017. The GFR was measured by isotopic technique and calculated using the Cockroft-Gault, Schwartz equations and 3 other formula. RESULTS: For the 34 AN patients, mean BMI -2.7 zscore, the mean measured GFR was 107+/-26 mL/min/1.73 m2. Among them, 35% (12/34) had a GFR under 90 mL/min/1.73 m2. The calculated GFR with Cockroft-Gault formula had the best correlation with the measured GFR (R2 = 0.852), whatever the creatinine level. No correlation was found between creatinine level and measured GFR. CONCLUSION: Kidney dysfunction is common in malnourished AN adolescents, so clinicians should always evaluate AN patients for renal impairments. Creatinine level is a poor indicator of renal function in this population. The most accurate formula to test GFR with a simple blood test is the Cockroft-Gault formula.

Validation of the "Good2Go": the first French-language transition readiness questionnaire.

The use of transition readiness questionnaires is strongly recommended in adolescents with chronic conditions. The aim of our study was to validate "Good2Go," the first French-language transition readiness questionnaire. We analyzed the data from 2 multicentric studies (Canada and France) involving adolescents with chronic conditions (type 1 diabetes, inflammatory bowel disease, cystic fibrosis, epilepsy, juvenile idiopathic arthritis). Content and construct validity were examined using factorial and Rasch analysis (structural validity), Spearman's correlation, and Mann-Whitney test (external validity). Cronbach's α and intra-class correlation coefficients explored reliability. Cognitive interviews assessed wording comprehension and item appropriateness. Good2Go was completed by 321 participants (boys = 51%; mean age = 16.4 years (standard deviation = 1.5; min = 14.0; max = 18.0); Canada = 51.1%). Factor analysis identified 3 domains: "health self-advocacy," "knowledge about chronic conditions," and "self-management skills." The 3-domain structure showed a satisfying Rasch fit, internal consistency, and test-retest reliability. Good2Go domain scores were significantly higher in participants over 17 years of age, indicating satisfactory external validity.Conclusion: Good2Go is a valid 20-item questionnaire to assess transition readiness in adolescents with chronic conditions and may be useful in routine care to propose individually tailored preparation for their transfer to adult healthcare. Further research is now needed to analyze correlation between domain scores and success of transition.What is Known:• In adolescents with chronic conditions, the use of transition readiness questionnaires is recommended to propose individually tailored preparation for their transfer to adult healthcare.• However, no French-language questionnaire has been so far validated.What is New:• Based on a complete validation methodology, this study highlights that the French-language 20-items Good2Go questionnaire has good psychometric properties.• It explores all transition key points though 3 scored domains: "health self-advocacy", "knowledge about chronic disease" and "self-management skills".

Incidence of cardiovascular events and risk markers in a prospective study of children diagnosed with Marfan syndrome.

BACKGROUND: Little is known about the incidence of cardiovascular events (CVEs) and their associated risk markers in children with Marfan syndrome (MFS). AIMS: To assess the incidence of CVEs and determine risk markers in a cohort diagnosed with Marfan syndrome during childhood and followed for several years. METHODS: From a French multicentre nationwide database, 462 patients with MFS diagnosed during childhood were included prospectively. Patients' files were screened for a period of 20 years (1993-2013). CVEs (e.g. death, aortic dissection, cardiac valve or aortic root surgery) were assessed during the prospective follow-up. RESULTS: Median (interquartile range) age at the end of follow-up was 17.2 (11.1-21.3) years. CVEs were reported for 35 participants (7.6%; 95% confidence interval [CI] 5.3-10.4%). First CVEs were prophylactic aortic root surgery (n=29), aortic dissection (n=4; two aged <18 years) and death (n=2). Kaplan-Meier cumulative incidence of CVEs was 5.3% (95% CI 3.3-8.7%) during childhood (aged≤18 years) and 19.4% (95% CI 13.3-27.9%) at 25years of age. The cumulative rate of CVEs was higher in case of Valsalva sinus Z-score increase of≥0.1 per year (P=0.0003), maximal Valsalva sinus diameter growth speed ≥5mm per year (P=0.03), aortic regurgitation≥2 (P=0.0005) and maximal Valsalva sinus Z-score≥3 before 16 years of age (P<0.0001). In a multivariable Cox proportional analysis, the Valsalva sinus Z-score remained significantly related to outcome. Considering aortic root evolution, aortic regurgitation, age at diagnosis and beta-blocker therapy were related to Valsalva sinus Z-score evolution during follow-up. CONCLUSIONS: CVEs in children with MFS are mainly related to prophylactic aortic root surgery. Aortic dissections are rarely observed in children. The Valsalva sinus Z-score is a strong indicator of subsequent CVEs in children with MFS. Attention to follow-up and beta-blocker observance may be warranted in high-risk children.

Renal injury in pediatric anorexia nervosa: a retrospective study.

PURPOSE: Although primarily a mental health disorder, anorexia nervosa (AN) has many physical consequences. Among them, the consequences on kidney function are often underestimated. We evaluated renal function in adolescent AN inpatients and investigated the correlation between the GFR and intrinsic patient characteristics. METHODS: A single-center retrospective study was conducted on 51 patients hospitalized for the restrictive type of AN in 2013. Data were divided into: (1) medical history of AN; (2) growth parameters and vital signs upon admission; and (3) blood tests. The glomerular filtration rate (GFR) was calculated using the Cockroft-Gault, MAYO Clinical Quadratic (MCQ), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), the Modification of Diet in Renal Disease (MDRD), and Schwartz equations. RESULTS: The calculated percentages of patients with a GFR below 90 mL/min/1.73 m2 according to the different equations were as follows: Cockroft-Gault, 45%; MDRD, 28%; CKD-EPI, 14%; MCQ, 12%, and Schwartz, 4%. There was a strong association between the body mass index (BMI) and the GFR according to all equations (p < 0.0001). The lowest heart rate was significantly associated with a reduced GFR according to the Cockroft-Gault equation (p = 0.03). The GFR values did not differ significantly after rehydration. CONCLUSION: Clinicians should evaluate AN patients for renal complications, especially when the BMI and heart rate are very low. Dehydration was not solely responsible for renal impairment. LEVEL OF EVIDENCE: Level III, single-center retrospective cohort study.

Association of modifiers and other genetic factors explain Marfan syndrome clinical variability.

Marfan syndrome (MFS) is a rare autosomal dominant connective tissue disorder related to variants in the FBN1 gene. Prognosis is related to aortic risk of dissection following aneurysm. MFS clinical variability is notable, for age of onset as well as severity and number of clinical manifestations. To identify genetic modifiers, we combined genome-wide approaches in 1070 clinically well-characterized FBN1 disease-causing variant carriers: (1) an FBN1 eQTL analysis in 80 fibroblasts of FBN1 stop variant carriers, (2) a linkage analysis, (3) a kinship matrix association study in 14 clinically concordant and discordant sib-pairs, (4) a genome-wide association study and (5) a whole exome sequencing in 98 extreme phenotype samples.Three genetic mechanisms of variability were found. A new genotype/phenotype correlation with an excess of loss-of-cysteine variants (P = 0.004) in severely affected subjects. A second pathogenic event in another thoracic aortic aneurysm gene or the COL4A1 gene (known to be involved in cerebral aneurysm) was found in nine individuals. A polygenic model involving at least nine modifier loci (named gMod-M1-9) was observed through cross-mapping of results. Notably, gMod-M2 which co-localizes with PRKG1, in which activating variants have already been described in thoracic aortic aneurysm, and gMod-M3 co-localized with a metalloprotease (proteins of extra-cellular matrix regulation) cluster. Our results represent a major advance in understanding the complex genetic architecture of MFS and provide the first steps toward prediction of clinical evolution.

Human Papillomavirus vaccination in general practice in France, three years after the implementation of a targeted vaccine recommendation based on age and sexual history.

In France, vaccination against human papilloma virus (HPV) was recommended in 2007 for all 14-year-old girls as well as "catch-up" vaccination for girls between 15-23 y of age either before or within one year of becoming sexually active. We evaluated the vaccine coverage according to the eligibility for vaccination in a sample of young girls aged 14 to 23 years, who were seen in general practices. A survey was proposed to 706 general practitioners (GPs) and carried out from July to September 2010. GPs, also called "family doctor," are physicians whose practice is not restricted to a specific field of medicine but instead covers a variety of medical problems in patients of all ages. Each participating GP included, retrospectively, the last female patient aged 14-17 y and the last female patient aged 18-23 y whom he had seen. A questionnaire collected information regarding the GP and the patients' characteristics. The vaccine coverage was determined according to the eligibility for vaccination, i.e. the coverage among younger women (14-17) and among those sexually active in the second age range (18-23). Sexual activity status was assessed by GP, according to information stated in the medical record. The 363 participating physicians (response rate 51.4%) included 712 patients (357 in the 14- to 17-year-old group and 355 in the 15- to 23-year-old group) in their responses. The rate of the vaccination coverage in the 14- to 17-year-old group was 55%. Among the girls in the 18- to 23-year-old group, 126 were eligible, and their vaccination coverage rate was 82%. The evaluation of the eligibility by the GPs was incorrect in 36% of the cases. Of the 712 patients, 6% of the girls had been vaccinated without a need for the vaccination, and 26% of the girls had not been vaccinated, although they needed to be vaccinated. Regarding the vaccine uptake, vaccination at the age of 14 was not as effective as vaccinating the older population for which vaccination was indicated as a catch-up program, based on sexual history. However, in more than one-third of the older population, difficulties remained regarding the determination of eligibility, according to the sexual history of the patient.

Aortic Dilatation Associated With a De Novo Mutation in the SOX18 Gene: Expanding the Clinical Spectrum of Hypotrichosis-Lymphedema-Telangiectasia Syndrome.

BACKGROUND: We report a 13-year-old female patient followed since birth for multiple rare congenital defects, including hypotrichosis, telangiectasia, and severe dilatation of the ascending aorta. METHODS: Comprehensive phenotype assessment throughout childhood included repeated echocardiographic measurements, evaluation of renal function, and immunohistochemical analysis of skin biopsy samples. Whole-exome sequencing was performed for the patient and both unaffected parents. RESULTS: We identified a novel de novo mutation in the transcription factor SOX18 (c.481C>T:p.Gln161*) in the patient, which was absent in all unaffected family members. Echocardiography revealed early onset and progressive dilatation of the ascending aorta. Skin biopsy results confirmed the defects of the blood vasculature in the presence of intact lymphatic vessels. Assessment of renal function did not show any signs of renal problems or renal failure in the patient. CONCLUSIONS: The genetic finding of a pathogenic SOX18 mutation enabled the diagnosis of the rare hypotrichosis-lymphedema-telangiectasia syndrome in our patient. The identification of a novel stop gain mutation in the SOX18 gene in association with dilatation of the aorta highlights the importance of this gene during the development of the circulatory system. Our study highlights the importance of whole-exome sequencing in the rapid identification of genes and gene mutations involved in rare conditions and thus expanding the knowledge and spectrum of clinical manifestations associated with them.

Cannabinoid Hyperemesis Syndrome in a 17-Year-Old Adolescent.

Cannabis is the most widely used illicit drug in the world. In Canada, cannabis use has been decreasing among youth since 2008. However, it is still two times more prevalent than among adults. A distinct syndrome, characterized by recurrent vomiting associated with abdominal pain and compulsive bathing, has been increasingly recognized in chronic adult users. The cannabinoid hyperemesis syndrome (CHS) is still underdiagnosed among adults and even more among adolescents. The authors describe the case of a 17-year-old adolescent, who sought emergency care five times over a year for uncontrolled nausea, profuse vomiting, and weight loss. The patient's symptoms were ameliorated by repetitive hot showering and by avoiding cannabis use. Cannabinoid hyperemesis syndrome is a clinical diagnosis and should be consider in every case of cyclical vomiting. A review of the clinical aspects and the treatment is presented here.

Somatic outcome among patients hospitalised for anorexia nervosa in adolescence: disorders reported and links with global outcome.

AIMS: (1) To describe the frequency of somatic pathologies and depression among former anorexia nervosa (AN) patients; (2) to study links with subjects' clinical history and global outcomes. METHODS: 97 women hospitalised for AN during adolescence, 9.00 ± 1.92 years previously, were interviewed using structured questionnaires concerning somatic and psychiatric disorders that they had experienced. RESULTS: Iron deficiency, migraine, cystitis, upper digestive system disorders, fractures, osteoporosis, and dental problems were reported with a frequency >20 %. Depression was reported by 2/3 of the sample. Osteoporosis was 14 times more frequent in case of vitamin D deficiency. Fractures were three times more frequent in presence of osteoporosis and less frequent when the overall outcome was better. CONCLUSION: Among women who had AN in adolescence, somatic comorbidities are frequent in adulthood. They are linked to the severity and the duration of AN, and to the overall outcome of the subject.

Iron metabolism in patients with anorexia nervosa: elevated serum hepcidin concentrations in the absence of inflammation.

BACKGROUND: Only a few studies based on small cohorts have been carried out on iron status in anorexia nervosa (AN) patients. OBJECTIVE: The aim of this study was to evaluate the role of hepcidin in hyperferritinemia in AN adolescents. DESIGN: Twenty-seven adolescents hospitalized for AN in the pediatric inpatient unit of Ambroise Paré Academic Hospital were enrolled in the study. The control group comprised 11 patients. Hematologic variables and markers of iron status, including serum hepcidin, were measured before and after nutritional rehabilitation. RESULTS: The mean age of patients was 14.4 y. Except for 2 AN patients and 1 control patient, all patients presented normal hemoglobin, vitamin B-12, and folate concentrations. Markers of inflammation and cytokines were normal throughout the study. None of the muscular lysis markers were elevated. Most AN patients had normal serum iron concentrations on admission. Serum ferritin concentrations were significantly higher in patients than in control subjects (198 compared with 49 µg/L, respectively; P < 0.001). The median hepcidin concentration was significantly higher in AN patients than in the control group (186.5 compared with 39.5 µg/L, respectively; P = 0.002). There was a highly significant correlation between ferritinemia and serum hepcidin concentrations (P < 0.0001). After nutritional rehabilitation, a significant reduction was observed (P = 0.004) in serum ferritin. Serum hepcidin analyzed in a smaller number of patients also returned to within the normal range. CONCLUSIONS: Hepcidin and ferritin concentrations were higher in the serum of AN patients, without any evidence of iron overload or inflammation. These concentrations returned to normal after nutritional rehabilitation. These results suggest that nutritional stress induced by malnourishment in the hepatocyte could be yet another mechanism that regulates hepcidin.

Cardiovascular manifestations in men and women carrying a FBN1 mutation.

AIMS: In patients with Marfan syndrome and other type-1 fibrillinopathies, genetic testing is becoming more easily available, leading to the identification of mutations early in the course of the disease. This study evaluates the cardiovascular (CV) risk associated with the discovery of a fibrillin-1 (FBN1) mutation. METHODS AND RESULTS: A total of 1,013 probands with pathogenic FBN1 mutations were included, among whom 965 patients [median age: 22 years (11-34), male gender 53%] had data suitable for analysis. The percentage of patients with an ascending aortic (AA) dilatation increased steadily with increasing age and reached 96% (95% CI: 94-97%) by 60 years. The presence of aortic events (dissection or prophylactic surgery) was rare before 20 years and then increased progressively, reaching 74% (95% CI: 67-81%) by 60 years. Compared with women, men were at higher risk for AA dilatation [≤ 30 years: 57% (95% CI: 52-63) vs. 50% (95% CI: 45-55), P = 0.0076] and aortic events [≤ 30 years: 21% (95% CI: 17-26) vs. 11% (95% CI: 8-16), P < 0.0001; adjusted HR: 1.4 (1.1-1.8), P = 0.005]. The prevalence of mitral valve (MV) prolapse [≤ 60 years: 77% (95% CI: 72-82)] and MV regurgitation [≤ 60 years: 61% (95% CI: 53-69)] also increased steadily with age, but surgery limited to the MV remained rare [≤ 60 years: 13% (95% CI: 8-21)]. No difference between genders was observed (for all P> 0.20). From 1985 to 2005 the prevalence of AA dilatation remained stable (P for trend = 0.88), whereas the percentage of patients with AA dissection significantly decreased (P for trend = 0.01). CONCLUSION: The CV risk remains important in patients with an FBN1 gene mutation and is present throughout life, justifying regular aortic monitoring. Aortic dilatation or dissection should always trigger suspicion of a genetic background leading to thorough examination for extra-aortic features and comprehensive pedigree investigation.

Comparison of clinical presentations and outcomes between patients with TGFBR2 and FBN1 mutations in Marfan syndrome and related disorders.

BACKGROUND: TGFBR2 mutations were recognized recently among patients with a Marfan-like phenotype. The associated clinical and prognostic spectra remain unclear. METHODS AND RESULTS: Clinical features and outcomes of 71 patients with a TGFBR2 mutation (TGFBR2 group) were compared with 50 age- and sex-matched unaffected family members (control subjects) and 243 patients harboring FBN1 mutations (FBN1 group). Aortic dilatation was present in a similar proportion of patients in both the TGFBR2 and FBN1 groups (78% versus 79%, respectively) but was highly variable. The incidence and average age for thoracic aortic surgery (31% versus 27% and 35+/-16 versus 39+/-13 years, respectively) and aortic dissection (14% versus 10% and 38+/-12 versus 39+/-9 years) were also similar in the 2 groups. Mitral valve involvement (myxomatous, prolapse, mitral regurgitation) was less frequent in the TGFBR2 than in the FBN1 group (all P<0.05). Aortic dilatation, dissection, or sudden death was the index event leading to genetic diagnosis in 65% of families with TGFBR2 mutations, versus 32% with FBN1 mutations (P=0.002). The rate of death was greater in TGFBR2 families before diagnosis but similar once the disease had been recognized. Most pregnancies were uneventful (without death or aortic dissection) in both TGFBR2 and FBN1 families (38 of 39 versus 213 of 217; P=1). Seven patients (10%) with a TGFBR2 mutation fulfilled international criteria for Marfan syndrome, 3 of whom presented with features specific for Loeys-Dietz syndrome. CONCLUSIONS: Clinical outcomes appear similar between treated patients with TGFBR2 mutations and individuals with FBN1 mutations. Prognosis depends on clinical disease expression and treatment rather than simply the presence of a TGFBR2 gene mutation.

Clinical and molecular study of 320 children with Marfan syndrome and related type I fibrillinopathies in a series of 1009 probands with pathogenic FBN1 mutations.

From a large series of 1009 probands with pathogenic FBN1 mutations, data for 320 patients <18 years of age at the last follow-up evaluation were analyzed (32%). At the time of diagnosis, the median age was 6.5 years. At the last examination, the population was classified as follows: neonatal Marfan syndrome, 14%; severe Marfan syndrome, 19%; classic Marfan syndrome, 32%; probable Marfan syndrome, 35%. Seventy-one percent had ascending aortic dilation, 55% ectopia lentis, and 28% major skeletal system involvement. Even when aortic complications existed in childhood, the rates of aortic surgery and aortic dissection remained low (5% and 1%, respectively). Some diagnostic features (major skeletal system involvement, striae, dural ectasia, and family history) were more frequent in the 10- to <18-year age group, whereas others (ascending aortic dilation and mitral abnormalities) were more frequent in the population with neonatal Marfan syndrome. Only 56% of children could be classified as having Marfan syndrome, according to international criteria, at their last follow-up evaluation when the presence of a FBN1 mutation was not considered as a major feature, with increasing frequency in the older age groups. Eighty-five percent of child probands fulfilled international criteria after molecular studies, which indicates that the discovery of a FBN1 mutation can be a valuable diagnostic aid in uncertain cases. The distributions of mutation types and locations in this pediatric series revealed large proportions of probands carrying mutations located in exons 24 to 32 (33%) and in-frame mutations (75%). Apart from lethal neonatal Marfan syndrome, we confirm that the majority of clinical manifestations of Marfan syndrome increase with age, which emphasizes the poor applicability of the international criteria to this diagnosis in childhood and the need for follow-up monitoring in cases of clinical suspicion of Marfan syndrome.

Achondroplasia: from genotype to phenotype.

This review focuses on the rheumatological features of achondroplasia, which is the most common skeletal dysplasia and the most frequent cause of short-limbed dwarfism. It is inherited in an autosomal dominant manner but results in the majority of cases of de novo mutations. The disease is related to a mutation in the fibroblast growth factor receptor-3 (FGFR3) gene encoding one member of the FGFR subfamily of tyrosine kinase receptors, which results in constitutive activation of the receptor. Biochemical studies of FGFR3 combined with experiments in knock-out mice have demonstrated that FGFR3 is a negative regulator of chondrocytes proliferation and differentiation in growth plate. This mutation induces a disturbance of endochondral bone formation. The diagnosis of achondroplasia is based on typical clinical and radiological features including short stature, macrocephaly with frontal bossing, midface hypoplasia and rhizomelic shortening of the limbs. The most common rheumatological complications of achondroplasia are medullar and radicular compressions due to spinal stenosis and deformities of the lower limbs. Current treatment and future therapies are discussed.

[Preventive clinical messages for children from 0 to 3 years of age]. / Les grands messages de prévention de 0 a 3 ans.

Prevention is a part of the medical visit during this critical period. The main preventive messages for children up to 3 years concern the immediate environment of the child and its consequences on his health. Sleeping position, passive tobacco use, his nutrition: prevention of infantile obesity, food imbalances, impairment of the mother to child relationship. Hygiene procedures have to be discussed with the families. Injury prevention is based on the vigilance of the human entourage, the safety environment, more than eventual modifications of the child behaviour. The detection of lead exposed children is a public health priority so the consequences are fearsome. The knowledge of the seriousness signs of the usual diseases is the basis oh health education to achieve two goals: behaviours to adopt to avoid the complication, early diagnosis of complications.