Brazilian Doctor's Perspective On The Second Opinion Strategy Before A C-section

Objective: To describe the opinion of doctors who participated in the Latin American Study on Cesarean section in Brazil regarding the second opinion strategy when faced with the decision of performing a C-section. Methods: Seventy-two doctors from the hospitals where the study took place (where the second opinion was routinely sought) and 70 from the control group answered a pre-tested self-administered structured questionnaire. Descriptive tables were prepared based on the frequency of relevant variables on opinion of physicians regarding: effectiveness of the application of the second opinion strategy; on whether they would recommend implementation of this strategy and reasons for not recommending it in private institutions; feasibility of the strategy implementation and reasons for not considering this implementation feasible in private institutions. Results: Half of the doctors from the intervention hospitals (50%) and about two thirds of those in the control group (65%) evaluated the second opinion as being or having the potential of being effective/very effective in their institutions. The great majority of those interviewed from both intervention and control hospitals considered this strategy feasible in public (87% and 95% respectively) but not in private hospitals (64% and 70% respectively), mainly because in the latter the doctors would not accept interference from a colleague in their decision-making process. Conclusion: Although the second opinion strategy was perceived as effective in reducing C-section rates, doctors did not regard it feasible outside the public health system in Brazil. © 2006 Faculdade de Saúde Pública da Universidade de Sao Paulo.402233239Althabe, F., Belizan, J.M., Villar, J., Alexander, S., Bergel, E., Ramos, S., Mandatory second opinion to reduce rates of unnecessary caesarean sections in Latin America: A cluster randomised controlled trial (2004) Lancet, 363 (9425), pp. 1934-1940Belizan, J., Althabe, F., Barros, F.C., Alexander, S., Rates and implications of caesarean sections in Latin America: Ecological study (1999) BMJ, 319 (7222), pp. 1397-1402Chacham, A.S., Perpétuo, I.H.O., The incidence of caesarean deliveries in Belo Horizonte, Brazil: Social and economic determinants (1998) Reprod Health Matters, 6 (11), pp. 115-121Faúndes, A., Perpétuo, I.H.O., Cesárea por conveniência e a ética médica (2002) Ser Médico, 5 (19), pp. 32-34Faúndes, A., Pádua, K.S., Osis, M.J.D., Cecatti, J.G., Sousa, M.H., Opiniāo de mulheres e médicos brasileiros sobre a preferência pela via de parto (2004) Rev Saúde Pública, 38 (4), pp. 488-494Hopkins, K., Are brazilian women really choosing to deliver by cesarean? (2000) Soc Sci Med, 51 (5), pp. 725-740Mello e Souza, C., C-sections as ideal births: The cultural constructions of beneficence and patients' rights in Brazil (1994) Camb Q Healthc Ethics, 3 (3), pp. 358-366Moraes, M.S., Goldenberg, P., Cesáreas: Um perfil epidêmico (2001) Cad Saúde Pública, 17 (3), pp. 509-519Murray, S., Relation between private health insurance and high rates of caesarean section in Chile: Qualitative and quantitative study (2000) BMJ, 321 (7275), pp. 1501-1505Myers, S.A., Gleicher, N., A successful program to lower cesarean-section rates (1988) N Engl J Med, 319 (23), pp. 1511-1516(1998), 1. , Organización Panamericana de la Salud - OPAS. La salud en las Americas. Washington (DC)Osis, M.J.D., Pádua, K.S., Duarte, G.A., Souza, T.R., Faúndes, A., The opinion of brazilian women regarding vaginal labor and cesarean section (2001) Int J Gynaecol Obstet, 75 (SUPPL. 1), pp. S59-S66Penna, L., Arulkumaran, S., Cesarean section for non-medical reasons (2003) Int J Gynaecol Obstet, 82 (3), pp. 399-409Potter, J.E., Berquó, E., Perpétuo, I.H.O., Leal, O.F., Hopkins, K., Souza, M.R., Unwanted caesarean sections among public and private patients in Brazil: Prospective study (2001) BMJ, 323 (7322), pp. 1155-1158Rattner, D., Sobre a hipótese de estabilizaçāo das taxas de cesárea do estado de São Paulo, Brasil (1996) Rev Saúde Pública, 30 (1), pp. 19-33Schenker, J.G., Cain, J.M., FIGO committee report: FIGO committee for the ethical aspects of human reproduction and women's health (1999) Int J Gynaecol Obstet, 64 (3), pp. 317-322Sloan, N.L., Pinto, E., Calle, A., Langer, A., Winikoff, B., Fassihian, G., Reduction of cesarean delivery rate in Ecuador (2000) Int J Gynaecol Obstet, 69 (3), pp. 229-236Walker, R., Turnbull, D., Wilkinson, C., Strategies to address global cesarean section rates: A review of the evidence (2002) Birth, 29 (1), pp. 28-39Wolfe, S., Unnecessary cesarean sections: Curing a national epidemic (1994) Public Citiz Health Res Group, 10, pp. 1-

Brazilian obstetrician-gynecologists and abortion: a survey of knowledge, opinions and practices

BACKGROUND: Abortion laws are extremely restrictive in Brazil. The knowledge, opinions of abortion laws, and abortion practices of obstetrician-gynecologists can have a significant impact on women's access to safe abortion. METHODS: We conducted a mail-in survey with a 10% random sample of obstetrician-gynecologists affiliated with the Brazilian Federation of Obstetricians and Gynecologists. We documented participants' experiences performing abortion under a range of legal and illegal circumstances, and asked about which abortion techniques they had experience with. We used chi-square tests and crude logistic regression models to determine which sociodemographic, knowledge-related, or practice-related variables were associated with physician opinion. RESULTS: Of the 1,500 questionnaires that we mailed out, we received responses from 572 (38%). Less than half (48%) of the respondents reported accurate knowledge about abortion law and 77% thought that the law should be more liberal. One-third of respondents reported having previous experience performing an abortion, and very few of these physicians reported having experience with manual vacuum aspiration (MVA) or with misoprostol with either mifepristone or methotrexate. Physicians that favored liberalization of the law were more likely to have correct knowledge about abortion law, and to be in favor of public funding for abortion services. CONCLUSION: Brazilian obstetrician-gynecologists need more information on abortion laws and on safe, effective abortion procedures

Neonatal Near Miss Approach In The 2005 Who Global Survey Brazil

Objectives: To explore the use of the neonatal near miss concept as a tool to evaluate the quality of neonatal care, as 3 million early neonatal deaths occur every year around the world and the majority of these deaths are avoidable and take place in developing countries. Methods: This is a secondary analysis of the 2005 WHO Global Survey on Maternal and Perinatal Health, a cross-sectional study, using data from 19 randomly selected Brazilian hospitals. A pragmatic definition of neonatal near miss was developed and tested. Near miss indicators were calculated. Results: Among the 15,169 live born infants included in this analysis, 424 presented at least one of the following conditions: very low birth weight, less than 30 gestational weeks at birth or an Apgar score at the 5th minute of life less than 7. According to the operational definition, these survivors from life-threatening conditions were considered neonatal near miss cases. The early neonatal mortality rate was 8.2/1,000 live births, the neonatal near miss rate was 21.4 neonatal near miss cases/1,000 live births. Substantial variations in the mortality among neonates with life-threatening conditions at birth were observed suggesting intra-hospital quality of care issues. Conclusion: The near miss concept and indicators provided information that could be useful to evaluate the quality of care and set priorities for further assessments and health care improvement for newborn infants. Copyright © 2010 by Sociedade Brasileira de Pediatria.8612126(2004) State of the world's children 2005, , UNICEF, New York: UNICEFLawn, J.E., Cousens, S., Zupan, J., Lancet Neonatal Survival Steering Team. 4 million neonatal deaths: When? Where? Why? (2005) Lancet, 365, pp. 891-900Brazil, (2008) Estimates of mortality, , http://tabnet.datasus.gov.br/cgi/idb2007/matriz.htm#mort.Access:20/02/2009, Brazil:, websiteAraújo, B.F., Bozzetti, M.C., Tanaka, A.C., Early neonatal mortality in Caxias do Sul: A cohort study (2000) J Pediatr (Rio J), 76, pp. 200-206Sarquis, A.L., Miyaki, M., Cat, M.N., The use of CRIB score for predicting neonatal mortality risk (2002) J Pediatr (Rio J), 78, pp. 225-229Sarinho, S.W., Filho, D.A., Silva, G.A., Lima, M.C., Risk factors for neonatal death in Recife: A case-control study (2001) J Pediatr (Rio J), 77, pp. 294-298Castro, E.C., Leite, A.J., Hospital mortality rates of infants with birth weight less than or equal to 1,500 g in the northeast of Brazil (2007) J Pediatr (Rio J), 83, pp. 27-32Say, L., Pattinson, R.C., Gülmezoglu, A.M., WHO systematic review of maternal morbidity and mortality: The prevalence of severe acute maternal morbidity (near miss) (2004) Reprod Health, 1, p. 3Pattinson, R.C., Hall, M., Near misses: A useful adjunct to maternal death enquiries (2003) Br Med Bull, 67, pp. 231-243Say, L., Souza, J.P., Pattinson, R.C., WHO working group on Maternal Mortality and Morbidity classifications. Maternal near miss: Towards a standard tool for monitoring quality of maternal health care (2009) Best Pract Res Clin Obstet Gynaecol, 23, pp. 287-296Skinner, J.R., Chung, S.K., Montgomery, D., McCulley, C.H., Crawford, J., French, J., Near-miss SIDS due to Brugada syndrome (2005) Arch Dis Child, 90, pp. 528-529Avenant, T., Neonatal near miss: A measure of the quality of obstetric care (2009) Best Pract Res Clin Obstet Gynaecol, 23, pp. 369-374Villar, J., Valladares, E., Wojdyla, D., Zavaleta, N., Carroli, G., Velazco, A., WHO 2005 global survey on maternal and perinatal health research group. Caesarean delivery rates and pregnancy outcomes: The 2005 WHO global survey on maternal and perinatal health in Latin America (2006) Lancet, 367, pp. 1819-1829Shah, A., Faundes, A., Machoki, M., Bataglia, V., Amokrane, F., Donner, A., Methodological considerations in implementing the WHO Global Survey for Monitoring Maternal and Perinatal Health (2008) Bull World Health Organ, 86, pp. 126-131JP Souza, Cecatti JG, Faundes A, Morais SS, Villar J, Carroli G, et al. WHO 2005 global survey on maternal and perinatal health research group. Maternal near miss and maternal death in the 2005 WHO global survey on maternal and perinatal health. Bull WHO, 2009. [website] http://www.who.int/bulletin/88/2/08-057828.pdf. Access: 19/08/2009Parry, G., Tucker, J., Tarnow-Mordi, W., The CRIB (Clinical Risk Index for Babies) Score: A tool for assessing initial neonatal risk and comparing performance of neonatal intensive-care units (1993) Lancet, 342, pp. 193-19

Reassessing risk assessment: Limits to predicting reproductive tract infection in new contraceptive users

The high costs and technical complexity of testing for reproductive tract infection make routine screening difficult in resource-poor reproductive health service environments. An analysis of 407 women visiting a Brazilian family planning clinic to initiate contraceptive use finds that 35% had reproductive tract infections, with bacterial vaginosis (26%) and chlamydia (7%) the most common types of infection. Only a history of sexually transmitted diseases and fewer years of education were significantly associated with having an infection of the reproductive tract However, 95% of infections occurred among women who met neither of these risk criteria. The findings highlight the need for further research on cost-effective strategies for identifying women at risk for reproductive tract infection.23417918

Brazilian abortion law: the opinion of judges and prosecutors

OBJECTIVE: To analyze the opinion of judges and prosecutors concerning Brazilian abortion law and situations in which the abortion should be allowed. METHODS: A cross-sectional study was performed with 1,493 judges and 2,614 prosecutors in Brazil between 2005 and 2006. Participants completed a structured questionnaire approaching sociodemographic characteristics, opinions about abortion law, and circumstances in which abortion is considered lawful. Bivariate and multivariate analyses of data were carried out through Poisson regression. RESULTS: The majority of participants (78%) found that the circumstances in which abortion is considered lawful should be broadened, or even that abortion should not be criminalized. The highest rates of pro-abortion opinions resulted from: risk to the life of the mother (84%), anencephaly (83%), severe congenital malformation of fetus (82%), and pregnancy resulting from rape (82%). Variables related to religion were strongly associated to the opinion of participants. CONCLUSIONS: There is a trend in considering the need of changing the current abortion law, in the sense of widening the circumstances in which abortion is considered lawful, or even toward decriminalizing abortion, regardless of the circumstances in which it takes place.44340642

Consenso de la Rama de Genética de la Sociedad Chilena de Pediatría sobre las anomalías congénitas de mal pronóstico vital (ACMPV)

ResumenIntroducciónLa rama de genética de la Sociedad Chilena de Pediatría, en relación con el proyecto de ley que regula la despenalización de la interrupción voluntaria del embarazo en 3 causales, centrándose en la segunda causal que considera al «embrión o feto que padezca una alteración estructural congénita o genética incompatible con la vida extrauterina», se reunió para discutir conforme a la evidencia científica qué anomalías congénitas (AC) podrían ser incluidas en el proyecto de ley.MetodologíaLos expertos en genética clínica se centraron en 10 AC. Se efectuó revisión bibliográfica y una reunión extraordinaria para discutirla.ResultadosSe acordó no emplear el término «incompatible con la vida extrauterina», pues existen excepciones de sobrevidas más prolongadas y cambiar por «anomalía congénita de mal pronóstico vital (ACMPV)». Se evaluaron 10 AC: defectos graves de cierre del tubo neural: anencefalia, iniencefalia y craneorraquisquisis, hipoplasia pulmonar, feto acardio, ectopia cordis, triploidía no mosaico, complejo limb body wall, anomalía body stalk, trisomía 13, trisomía 18 y agenesia renal bilateral. Se analizaron los hallazgos sobre prevalencia, historia natural, métodos diagnósticos prenatales, sobrevida, casos descritos de sobrevida prolongada. Para catalogarlas como ACMPV se consideraron: sobrevida posnatal, existencia de tratamientos y evolución posterior e historia natural sin intervenciones.ConclusiónLas ACMPV incluidas serían: anencefalia, hipoplasia pulmonar severa, feto acardio, ectopia cordis cervical, triploidía no mosaico, complejo limb body wall, anomalía body stalk, trisomía 13 no mosaico, trisomía 18 no mosaico y agenesia renal bilateral. Se requiere para el diagnóstico que toda mujer gestante tenga acceso a evaluaciones ecográficas de anatomía fetal, y en ocasiones a resonancia magnética y estudios citogenéticos y moleculares.AbstractIntroductionThe Genetic Branch of the Chilean Society of Paediatrics, given the draft Law governing the decriminalisation of abortion on three grounds, focusing on the second ground, which considers the “embryo or foetus suffering from a congenital structural anomaly or a genetic disorder incompatible with life outside the womb”, met to discuss the scientific evidence according to which congenital anomalies (CA) may be included in this draft law.MethodologyExperts in clinical genetics focused on 10 CA, reviewed the literature evidence, and met to discuss it.ResultsIt was agreed not to use the term “incompatible with life outside the womb”, as there are exceptions and longer survivals, and change to “congenital anomaly of poor prognosis (CAPP)”. Ten CA were evaluated: serious defects of neural tube closure: anencephaly, iniencephaly and craniorachischisis, pulmonary hypoplasia, acardiac foetus, ectopia cordis, non-mosaic triploidy, “limb body wall” complex, “body stalk” anomaly, trisomy 13, trisomy 18, and bilateral renal agenesis. Findings on the prevalence, natural history, prenatal diagnostic methods, survival, and reported cases of prolonged survival were analysed. Post-natal survival, existence of treatments, and outcomes, as well as natural history without intervention, were taken into account in classifying a CA as a CAPP.ConclusionA CAPP would be: anencephaly, severe pulmonary hypoplasia, acardiac foetus, cervical ectopia cordis, non-mosaic triploidy, limb body wall complex, body stalk anomaly, non-mosaic trisomy 13, non-mosaic trisomy 18, and bilateral renal agenesis. For their diagnosis, it is required that all pregnant women have access to assessments by foetal anatomy ultrasound and occasionally MRI, and cytogenetic and molecular testing

Urinary Incontinence Among Climateric Brazilian Women: Household Survey

Objective. To investigate the prevalence of stress urinary incontinence and its associated factors in perimenopause women using a population-based household survey. Methods. A descriptive, exploratory cross-sectional population-based study with secondary analysis of a population-based household survey on perimenopause and menopause was conducted among women living in the city of Campinas, Brazil. Through a sampling process, 456 women between 45 and 60 years old were selected. Complaints of urinary incontinence and related risk factors, such as age, socioeconomic status, education level, race, parity, smoking habits, body mass index, previous gynecological surgeries, menopausal status, and hormonal replacement therapy were explored. Data were collected through home interviews using an adapted version of the structured pre-tested questionnaire elaborated by the International Health Foundation, International Menopause Society and the American Menopause Society. Statistical analysis were performed using prevalence rates (CI 95%). Results. Thirty-five percent of the interviewees referred stress urinary incontinence. None of the sociodemographic factors studied was associated to the risk of urinary incontinence. In addition, parity did not significantly change the risk of urinary incontinence. Other factors, such as previous gynecological surgeries, body mass index, and smoking habits, were not associated with the prevalence of stress urinary incontinence. Also, menopausal status and hormonal replacement therapy did not change the risk of stress urinary incontinence. Conclusion. Though there was a high prevalence of stress urinary incontinence among perimenopause women, there was not found any associations with sociodemographic and reproductive factors.355428435Bortolotti, A., Bernardini, B., Colli, E., Di Benedetto, P., Giocoli Nacci, G., Landoni, M., Prevalence and risk factors for urinary incontinence in Italy (2000) Eur Urol, 37, pp. 30-35Brown, J.S., Grady, D., Ouslander, J.G., Herzog, A.R., Varner, R.E., Posner, S.F., Prevalence of urinary incontinence and associated risk factors in postmenopausal women (1999) Obstet Gynecol, 94, pp. 66-70. , Hert & Estrogen/Progestin Replacement Study (HERS) Research GroupBurgio, K.L., Mathews, K.A., Engel, B.T., Prevalence, incidence and correlates of urinary incontinence in healthy, middle-aged women (1991) J Urol, 146, pp. 1255-1259Comportamento sexual da população brasileira e percepção sobre o HIV/AIDS: Relatório final de pesquisa (1999), pp. 34-37. , Centro Brasileiro de Análise e Planejamento (CEBRAP), Ministério da Saúde-SPS-CNDST/HIV/AIDS. São PauloChiarelli, P., Brown, W., Mc Elduf, F.P., Leaking urine: Prevalence and associated factors in Australian women (1999) Neurourol Urodyn, 18, pp. 567-577Elving, L.B., Foldspang, A., Lam, G.W., Mommsen, S., Descriptive epidemiology of urinary incontinence in 3100 women age 30-59 (1989) Scand J Urol Nephrol, 125 (SUPPL.), pp. 37-43Fantl, J.A., Cardozo, L., Mc Clish, D.K., Estrogen therapy in the management of urinary incontinence in postmenopausal women: A meta-analisys (1994) Obstet Gynecol, 83, pp. 12-18. , First report of the Hormones and Urogenital Therapy CommiteeFantl, J.A., Bump, R.C., Robinson, D., Efficacy of estrogen supplementation in the treatment of urinary incontinece (1996) Obstet Gynecol, 88, pp. 745-749Guarisi, T., Pinto-Neto, A.M., Costa-Paiva, L.H.S., Pedro, A.O., Faúndes, A., Sintomas urinários e genitais em mulheres climatéricas (1998) J Bras Ginecol, 108, pp. 125-130Jaszmann, L., Epidemiology of climateric and postclimateric complaints (1973), pp. 22-24. , Van Keep PA, Lauritzen C, editors. Ageing and estrogens: front hormone research. Basel: KargerLaurenti, R., Mello-Jorge, M.L.P., Lebrão, M.L., Gotlieb, S.L.D., População: Recenseamento e estimativas (1987) Estatística de saúde., pp. 9-38. , editors. 2a ed. São Paulo: EPUMendonça, M., Reis, R.V., Macedo, C.B.M.S., Barbosa, K.S.R., Prevalência da queixa de incontinência urinária de esforço em pacientes atendidas no serviço de ginecologia do Hospital Júlia Kubitschek (1997) J Bras Ginecol, 107, pp. 153-155Moller, L.A., Lose, G., Jorgensen, T., The prevalence and bothersomeness of lower urinary tract symptons in women 40-60 years of age (2000) Acta Obstet Gynecol Scand, 79, pp. 298-305Thom, D.H., Brown, J.S., Reproductive and hormonal risk factors for urinary incontinence in later life: A review of the clinical and epidemiologic literature (1998) J Am Geriatr Soc, 46, pp. 1411-1417Van Geelen, J.M., Van de Weijer, P.H., Arnolds, H.T., Urogenital symptons and resulting discomfort in noninstitutionalized Dutch women aged 50-75 years (2000) Int Urogynecol J Pelvic Floor Dysfunct, 11, pp. 9-14Von Mühlen, D.G., Kritz-Silverstein, D., Barret-Connor, E., A community based study of menopause symptoms and estrogen replacement in older women (1995) Maturitas, 22, pp. 71-78Wilbur, J., Miller, A.M., Montgomery, A., Chandler, P., Sociodemographic characteristics, biological factors, an symptom reporting in midlife women (1998) Menopause, 5, pp. 43-5

A restricted spectrum of missense KMT2D variants cause a multiple malformations disorder distinct from Kabuki syndrome

Purpose: To investigate if specific exon 38 or 39 KMT2D missense variants (MVs) cause a condition distinct from Kabuki syndrome type 1 (KS1). Methods: Multiple individuals, with MVs in exons 38 or 39 of KMT2D that encode a highly conserved region of 54 amino acids flanked by Val3527 and Lys3583, were identified and phenotyped. Functional tests were performed to study their pathogenicity and understand the disease mechanism. Results: The consistent clinical features of the affected individuals, from seven unrelated families, included choanal atresia, athelia or hypoplastic nipples, branchial sinus abnormalities, neck pits, lacrimal duct anomalies, hearing loss, external ear malformations, and thyroid abnormalities. None of the individuals had intellectual disability. The frequency of clinical features, objective software-based facial analysis metrics, and genome-wide peripheral blood DNA methylation patterns in these patients were significantly different from that of KS1. Circular dichroism spectroscopy indicated that these MVs perturb KMT2D secondary structure through an increased disordered to ɑ-helical transition. Conclusion: KMT2D MVs located in a specific region spanning exons 38 and 39 and affecting highly conserved residues cause a novel multiple malformations syndrome distinct from KS1. Unlike KMT2D haploinsufficiency in KS1, these MVs likely result in disease through a dominant negative mechanism.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.16-17/10/Newlife - The Charity for Disabled Children FS/13/32/30069/BHF_/British Heart Foundation/United Kingdom 72160007/Chile's National Commission for Scientific and Technological Research MR/K011154/1/MRC_/Medical Research Council/United Kingdom WT_/Wellcome Trust/United Kingdompre-prin

Socioeconomic and physical distance to the maternity hospital as predictors for place of delivery: an observation study from Nepal

BACKGROUND: Although the debate on the safety and women's right of choice to a home delivery vs. hospital delivery continues in the developed countries, an undesirable outcome of home delivery, such as high maternal and perinatal mortality, is documented in developing countries. The objective was to study whether socio-economic factors, distance to maternity hospital, ethnicity, type and size of family, obstetric history and antenatal care received in present pregnancy affected the choice between home and hospital delivery in a developing country. METHODS: This cross-sectional study was done during June, 2001 to January 2002 in an administratively and geographically well-defined territory with a population of 88,547, stretching from urban to adjacent rural part of Kathmandu and Dhading Districts of Nepal with maximum of 5 hrs of distance from Maternity hospital. There were no intermediate level of private or government hospital or maternity homes in the study area. Interviews were carried out on 308 women who delivered within 45 days of the date of the interview with a pre-tested structured questionnaire. RESULTS: A distance of more than one hour to the maternity hospital (OR = 7.9), low amenity score status (OR = 4.4), low education (OR = 2.9), multi-parity (OR = 2.4), and not seeking antenatal care in the present pregnancy (OR = 4.6) were statistically significantly associated with an increased risk of home delivery. Ethnicity, obstetric history, age of mother, ritual observance of menarche, type and size of family and who is head of household were not statistically significantly associated with the place of delivery. CONCLUSIONS: The socio-economic standing of the household was a stronger predictor of place of delivery compared to ethnicity, the internal family structure such as type and size of family, head of household, or observation of ritual days by the mother of an important event like menarche. The results suggested that mothers, who were in the low-socio-economic scale, delivered at home more frequently in a developing country like Nepal

Variability of systemic and oro-dental phenotype in two families with non-lethal Raine syndrome with FAM20C mutations

Background: Raine syndrome (RS) is a rare autosomal recessive bone dysplasia typified by osteosclerosis and dysmorphic facies due to FAM20C mutations. Initially reported as lethal in infancy, survival is possible into adulthood. We describe the molecular analysis and clinical phenotypes of five individuals from two consanguineous Brazilian families with attenuated Raine Syndrome with previously unreported features. Methods: The medical and dental clinical records were reviewed. Extracted deciduous and permanent teeth as well as oral soft tissues were analysed. Whole exome sequencing was undertaken and FAM20C cDNA sequenced in family 1. Results: Family 1 included 3 siblings with hypoplastic Amelogenesis Imperfecta (AI) (inherited abnormal dental enamel formation). Mild facial dysmorphism was noted in the absence of other obvious skeletal or growth abnormalities. A mild hypophosphataemia and soft tissue ectopic mineralization were present. A homozygous FAM20C donor splice site mutation (c.784 + 5 g > c) was identified which led to abnormal cDNA sequence. Family 2 included 2 siblings with hypoplastic AI and tooth dentine abnormalities as part of a more obvious syndrome with facial dysmorphism. There was hypophosphataemia, soft tissue ectopic mineralization, but no osteosclerosis. A homozygous missense mutation in FAM20C (c.1487C > T; p.P496L) was identified. Conclusions: The clinical phenotype of non-lethal Raine Syndrome is more variable, including between affected siblings, than previously described and an adverse impact on bone growth and health may not be a prominent feature. By contrast, a profound failure of dental enamel formation leading to a distinctive hypoplastic AI in all teeth should alert clinicians to the possibility of FAM20C mutations