Effect of high altitude on birth weight and adverse perinatal outcomes in two argentine populations

Introducción: existe poca información sobre la relación entre tamaño al nacer y altura geográfica ajustada para factores maternos y obstétricos potencialmente confusores. Objetivo: analizar la variación, en función de la altitud geográfica, del Peso al Nacimiento (PN) y resultados perinatales adversos, en dos poblaciones argentinas. Material y Métodos: 4000 registros de recién nacidos (RN) de Jujuy y 4000 de Buenos Aires (Maternidad Sardá) (1996-2000), seleccionados y aleatorizados del Sistema Informático Perinatal. Los datos provenían de la Maternidad Sarda (20 msnm) y las regiones jujeñas: Ramal (500 msnm), Valle (1200 msnm), Quebrada (2500 msnm) y Puna (3500 msnm). Variables resultado: PN >3000 g, PN 3000 g, PN 3000 g, BW 3000 g, BW<2500g and PI were negatively associated with altitude (p <0.001). Prematurity, SGA and FGR showed an opposite trend (p <0.001). Adjusted for confounding variables BW <3000 g, SGA, FGR<0.90 and PI <2.53 showed an increased risk with geographical altitude (p <0.05). Conclusions: Altitude was independently associated with BW restriction and adverse perinatal outcomes. Given the impact of BW reduction in the risk of chronic no communicable diseases this relationship in other populations, regardless of their location altitude, should be assess.Fil: Grandi, Carlos. Gobierno de la Ciudad de Buenos Aires. Maternidad Sardá; ArgentinaFil: Dipierri, Jose Edgardo. Universidad Nacional de Jujuy. Facultad de Humanidades y Ciencias Sociales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Luchtenberg, Guillermo. Gobierno de la Ciudad de Buenos Aires. Maternidad Sardá; ArgentinaFil: Moresco, Angélica. Gobierno de la Ciudad de Buenos Aires. Maternidad Sardá; ArgentinaFil: Alfaro Gómez, Emma Laura. Universidad Nacional de Jujuy; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Clinical and Genetic Spectrum of Stargardt Disease in Argentinean Patients

Purpose: To describe the clinical and molecular spectrum of Stargardt disease (STGD) in a cohort of Argentinean patients. Methods: This retrospective study included 132 subjects comprising 95 probands clinically diagnosed with STGD and relatives from 16 of them. Targeted next-generation sequencing of the coding and splicing regions of ABCA4 and other phenocopying genes (ELOVL4, PROM1, and CNGB3) was performed in 97 STGD patients. Results: We found two or more disease-causing variants in the ABCA4 gene in 69/95 (73%) probands, a single ABCA4 variant in 9/95 (9.5%) probands, and no ABCA4 variants in 17/95 (18%) probands. The final analysis identified 173 variants in ABCA4. Seventy-nine ABCA4 variants were unique, of which nine were novel. No significant findings were seen in the other evaluated genes. Conclusion: This study describes the phenotypic and genetic features of STGD1 in an Argentinean cohort. The mutations p.(Gly1961Glu) and p.(Arg1129Leu) were the most frequent, representing almost 20% of the mutated alleles. We also expanded the ABCA4 mutational spectrum with nine novel disease-causing variants, of which eight might be associated with South American natives.Fil: Mena, Marcela Daniela C. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Moresco, Angélica A.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Vidal, Sofía H.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Aguilar Cortes, Diana Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Obregon, María G.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Fandiño, Adriana Cristina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Sendoya, Juan Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Llera, Andrea Sabina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentin

Misoprostol teratogenicity : a prospective study in Argentina

Introducción.El misoprostol se emplea popularmente en la Argentina para intentar la interrupción del embarazo, pero cierta proporción de los embarazos continúa. Asimismo, diferentes informes mostraron asociación entre el misoprostol y defectos congénitos. Objetivos.Estimar el riesgo de anomalías congénitas en niños expuestos prenatalmente al misoprostol y conocer su forma de consumo durante la gestación. Método.Estudio de cohortes que comparó la frecuencia de aborto y de anomalías congénitas mayores en la descendencia de embarazadas expuestas al misoprostol (94) y de un grupo de embarazadas no expuestas (401), ambos grupos consultantes a un servicio de información sobre agentes teratogénicos. Resultados. Entre las mujeres expuestas al misoprostol solo el 8,2% lo compró con receta; el 81,5% se enteró de su efecto abortivo por una amiga, vecina o pariente; la dosis promedio fue 1439 mg; el 77,2% lo usó tanto por vía oral como vaginal; la edad gestacional promedio de consumo fue a los 48,5 días y el 35,2% empleó un agente abortivo adicional. Las mujeres expuestas al misoprostol presentaron una frecuencia significativamente mayor de abortos (expuestas: 17/94= 18,1%; no expuestas; 29/401= 7,2%; RR= 2,27; IC 95%:1,30-3,98), y de descendencia con anomalías congénitas mayores (expuestas: 5/77= 6,49%; no expuestas: 8/372= 2,15%; RR= 3,02; IC 95%:1,02-8,98). Los cinco niños malformados prenatalmente expuestos al misoprostol presentaron: 1) encefalocele y defectos transversales de miembros; 2) porencefalia; 3) malformación pulmonar adenomatosa quística; 4) encefalocele occipital y 5) malrotación intestinal. Conclusiones. El estudio detectó una asociación significativa entre la exposición prenatal a misoprostol y la ocurrencia de anomalías congénitas mayores.Introduction. Misoprostol is commonly used in Argentina to attempt abortion, although a certain proportion of pregnancies is not interrupted. On the other hand, various reports showed an association between misoprostol and congenital anomalies. Objectives.To estimate the risk of major congenital anomalies in children prenatally exposed to misoprostol, and to know their way of consumption during pregnancy. Method. A cohort study compared the frequency of abortion and major congenital abnormalities in offspring of pregnant women exposed to misoprostol (94) and an unexposed group of pregnant women (401), both groups consulting to a teratology information service. Results.Among women exposed to misoprostol only the 8.2% purchased it on prescription, 81.5% heard about its abortifacient effect by friends, neighbors or relatives, the average dose was 1.439 mg which was used both orally and vaginally by the 77.2%; the mean gestational age was 48.5 days and 35.2% used an additional abortive agent. Women exposed to misoprostol had a significantly higher frequency of abortions (exposed: 17/94= 18.1%, unexposed, 29/401= 7.2%, RR= 2.27, 95%: 1,30-3,98), and offspring with major congenital abnormalities (exposed: 5/77= 6.49%, unexposed: 8/372= 2.15%, RR= 3.02, 95%:1,02-8.98). The five malformed children prenatally exposed to misoprostol showed: 1) encephalocele and transverse limb defects; 2) porencephaly, 3) pulmonary adenomatous cystic malformation, 4) occipital encephalocele and, 5) intestinal malrotation. Conclusions.The study found a significant association between prenatal exposure to misoprostol and the occurrence of major congenital anomalies.Fil: Barbero, Pablo. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica Dr. Eduardo Castilla; Argentina.Fil: Liascovich, Rosa. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica Dr. Eduardo Castilla; Argentina.Fil: Valdez, Rita. FLENI. Departamento Neuropediatría; Argentina.Fil: Moresco, Angélica. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica Dr. Eduardo Castilla; Argentina

Misoprostol teratogenicity : a prospective study in Argentina

Introducción.El misoprostol se emplea popularmente en la Argentina para intentar la interrupción del embarazo, pero cierta proporción de los embarazos continúa. Asimismo, diferentes informes mostraron asociación entre el misoprostol y defectos congénitos. Objetivos.Estimar el riesgo de anomalías congénitas en niños expuestos prenatalmente al misoprostol y conocer su forma de consumo durante la gestación. Método.Estudio de cohortes que comparó la frecuencia de aborto y de anomalías congénitas mayores en la descendencia de embarazadas expuestas al misoprostol (94) y de un grupo de embarazadas no expuestas (401), ambos grupos consultantes a un servicio de información sobre agentes teratogénicos. Resultados. Entre las mujeres expuestas al misoprostol solo el 8,2% lo compró con receta; el 81,5% se enteró de su efecto abortivo por una amiga, vecina o pariente; la dosis promedio fue 1439 mg; el 77,2% lo usó tanto por vía oral como vaginal; la edad gestacional promedio de consumo fue a los 48,5 días y el 35,2% empleó un agente abortivo adicional. Las mujeres expuestas al misoprostol presentaron una frecuencia significativamente mayor de abortos (expuestas: 17/94= 18,1%; no expuestas; 29/401= 7,2%; RR= 2,27; IC 95%:1,30-3,98), y de descendencia con anomalías congénitas mayores (expuestas: 5/77= 6,49%; no expuestas: 8/372= 2,15%; RR= 3,02; IC 95%:1,02-8,98). Los cinco niños malformados prenatalmente expuestos al misoprostol presentaron: 1) encefalocele y defectos transversales de miembros; 2) porencefalia; 3) malformación pulmonar adenomatosa quística; 4) encefalocele occipital y 5) malrotación intestinal. Conclusiones. El estudio detectó una asociación significativa entre la exposición prenatal a misoprostol y la ocurrencia de anomalías congénitas mayores.Introduction. Misoprostol is commonly used in Argentina to attempt abortion, although a certain proportion of pregnancies is not interrupted. On the other hand, various reports showed an association between misoprostol and congenital anomalies. Objectives.To estimate the risk of major congenital anomalies in children prenatally exposed to misoprostol, and to know their way of consumption during pregnancy. Method. A cohort study compared the frequency of abortion and major congenital abnormalities in offspring of pregnant women exposed to misoprostol (94) and an unexposed group of pregnant women (401), both groups consulting to a teratology information service. Results.Among women exposed to misoprostol only the 8.2% purchased it on prescription, 81.5% heard about its abortifacient effect by friends, neighbors or relatives, the average dose was 1.439 mg which was used both orally and vaginally by the 77.2%; the mean gestational age was 48.5 days and 35.2% used an additional abortive agent. Women exposed to misoprostol had a significantly higher frequency of abortions (exposed: 17/94= 18.1%, unexposed, 29/401= 7.2%, RR= 2.27, 95%: 1,30-3,98), and offspring with major congenital abnormalities (exposed: 5/77= 6.49%, unexposed: 8/372= 2.15%, RR= 3.02, 95%:1,02-8.98). The five malformed children prenatally exposed to misoprostol showed: 1) encephalocele and transverse limb defects; 2) porencephaly, 3) pulmonary adenomatous cystic malformation, 4) occipital encephalocele and, 5) intestinal malrotation. Conclusions.The study found a significant association between prenatal exposure to misoprostol and the occurrence of major congenital anomalies.Fil: Barbero, Pablo. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica Dr. Eduardo Castilla; Argentina.Fil: Liascovich, Rosa. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica Dr. Eduardo Castilla; Argentina.Fil: Valdez, Rita. FLENI. Departamento Neuropediatría; Argentina.Fil: Moresco, Angélica. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica Dr. Eduardo Castilla; Argentina

Genotype–phenotype correlation of SMN locus genes in spinal muscular atrophy children from Argentina

Background/Purpose: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder, considered one of the leading causes of infant mortality. It is caused by mutations in the SMN1 gene. A highly homologous copy of this gene named SMN2 and other neighbouring genes, SERF1A and NAIP, are considered phenotypic modifiers of the disease. In recent years, notable advances have been made in SMA research regarding evaluation, prognosis, and therapeutic options. Thus, genotype-phenotype studies in SMA are important to stratify patients for motor function tests and for envisaged clinical trials. The aim of this study was to provide clinical and molecular data of a series of Argentinean children with SMA to establish a comprehensive genotype-phenotype correlation. Methods: 144 Argentinean children with SMA (56 children with type I, 58 with type II, and 30 with type III) were evaluated. The copy number of SMN2, SERF1A, and NAIP genes was established using MLPA (Multiplex Ligation-dependent Probe Amplification) and then correlated with the patients clinical subtypes. To improve clinical characterization we considered the initial symptoms that prompted the consultation, age of acquisition of motor abilities to independent walking and age at loss of gait. We also evaluated clinical and molecular features of sibling pairs in seven families. Results: A strong correlation was observed between the SMN2 copy number and SMA phenotype while SERF1A and NAIP copy number showed a moderate correlation. We observed intra- and inter-family differences among the SMA types. Conclusion: This first genotype-phenotype correlation study in Argentinean SMA children provides data to improve patient stratification and define more adequate follow-up parameters.Fil: Medrano, Sofía. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Monges, Soledad. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Gravina, Luis Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Alías, Laura. Hospital de la Santa Creu i Sant Pau; España. CIBERER; EspañaFil: Mozzoni, Julieta. Hospital de la Santa Creu i Sant Pau; EspañaFil: Aráoz, Hilda Verónica. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Bernal, Sara. Hospital de la Santa Creu i Sant Pau; España. CIBERER; EspañaFil: Moresco, Angélica. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Chertkoff, Lilien Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Tizzano, Eduardo. Hospital Valle Hebron; España. CIBERER; Españ

Ehlers-Danlos Syndrome: Molecular and Clinical Characterization of TNXA/TNXB Chimeras in Congenital Adrenal Hyperplasia

Context: The syndrome CAH-X is due to a contiguous gene deletion of CYP21A2 and TNXB resulting in TNXA/TNXB chimeras. Objective: To analyze TNXB gene status and to clinically evaluate the Ehlers-Danlos syndrome phenotype in a large cohort of Argentine congenital adrenal hyperplasia (CAH) patients to assess the prevalence of this condition in our population. Methods: TNXB gene analysis was performed in 66 nonrelated CAH patients that were carriers of the CYP21A2 gene deletion. A molecular strategy based on multiplex ligation-dependent probe amplification and Sanger sequencing analysis was developed allowing for the detection of different, previously described TNXA/TNXB chimeras, named CH1, CH2, and CH3. The main outcome measures were TNXB status of CAH patients that were carriers of the CYP21A2 deletion in the homozygous or heterozygous state. Results: TNXA/TNXB CH1 was found in 41%, CH2 in 29%, and CH3 in 1% of nonrelated alleles carrying the CYP21A2 deletion. Thus, overall 71% of alleles were found to carry a contiguous gene deletion. Sixty-seven percent of patients analyzed had a monoallelic form and 6% a biallelic form. All patients with the biallelic form had severe skin hyperextensibility and generalized joint hypermobility. Conclusion: Based on the high frequency of TNXB alterations found in CYP21A2 deletion carrier alleles, we recommend evaluating TNXB status in these patients, and assessing connective tissue dysplasia, including cardiologic alterations in positive cases. The number of patients undergoing cardiological evaluation should be expanded to determine the incidence of structural and functional abnormalities in this cohort.Fil: Marino, Roxana Marcela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Perez Garrido, Natalia Isabel. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Ramirez, Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Notaristéfano, Guillermo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Moresco, Angélica. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Touzon, María Sol. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Vaiani, Elisa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Finkielstain, Gabriela Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Obregón, María Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Balbi, Viviana. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Soria, Ianina. Provincia de La Rioja. Hospital de la Madre y el Niño; ArgentinaFil: Belgorosky, Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentin

O sistema hidrológico do Taim

O Sistema Hidrológico do Taim é um sistema límnico complexo composto de banhados e lagoas interconectadas. Esse sistema tem associado uma Unidade de Conservação Federal, a Estação Ecológica do Taim, e a cultura de arroz, a qual usa água do sistema para irrigação. A simultânea conservação do sistema com o uso da água é um desafio para a região, uma vez que ambos são dependentes do manejo da água. A gestão do sistema depende do entendimento de padrões e regimes. A água, na forma de hidroperíodo e hidrodinâmica, é a função de força dominante na formação, no estado e na evolução desse sistema hidrológico. Conhecer a assinatura hidrológica do sistema é fundamental para o entendimento da sua estrutura e do seu funcionamento. Essa assinatura influencia as comunidades biológicas e/ou espécies indicadoras. Padrões de comunidades acompanhadas no tempo permitem verificar a dinâmica oscilatória e a eventual mudança de regime em função de estressores antrópicos ou naturais, tanto na observação direta como por modelagem ecológica. O entendimento dos padrões espaciais e temporais no Sistema Hidrológico do Taim é a base para a proposta de uso e conservação simultânea.The Taim Hydrological System is a complex limnetic system composed of interconnected wetlands and lakes. This system has an associated federal conservation unit, the Taim Ecological Station, and rice cultivation, which uses water from the system for irrigation. Conservation of the system concomitantly with the use of its water is a challenge, since both functions depend on water management. The system management depends on understanding patterns and regimes. The hydroperiod and hydrodynamics are the dominant driving forces in the formation, evolution and current state of this hydrological system, and influence the biological communities and indicator species. Following the community patterns over time allows tracking of the oscillatory dynamics and possible regime change due to anthropogenic or natural stressors, both as direct observation or by ecological modeling. Understanding the spatial and temporal patterns in the Taim Hydrological System is the basis for the most efficient simultaneous use and conservation

O sistema hidrológico do Taim

O Sistema Hidrológico do Taim é um sistema límnico complexo composto de banhados e lagoas interconectadas. Esse sistema tem associado uma Unidade de Conservação Federal, a Estação Ecológica do Taim, e a cultura de arroz, a qual usa água do sistema para irrigação. A simultânea conservação do sistema com o uso da água é um desafio para a região, uma vez que ambos são dependentes do manejo da água. A gestão do sistema depende do entendimento de padrões e regimes. A água, na forma de hidroperíodo e hidrodinâmica, é a função de força dominante na formação, no estado e na evolução desse sistema hidrológico. Conhecer a assinatura hidrológica do sistema é fundamental para o entendimento da sua estrutura e do seu funcionamento. Essa assinatura influencia as comunidades biológicas e/ou espécies indicadoras. Padrões de comunidades acompanhadas no tempo permitem verificar a dinâmica oscilatória e a eventual mudança de regime em função de estressores antrópicos ou naturais, tanto na observação direta como por modelagem ecológica. O entendimento dos padrões espaciais e temporais no Sistema Hidrológico do Taim é a base para a proposta de uso e conservação simultânea.The Taim Hydrological System is a complex limnetic system composed of interconnected wetlands and lakes. This system has an associated federal conservation unit, the Taim Ecological Station, and rice cultivation, which uses water from the system for irrigation. Conservation of the system concomitantly with the use of its water is a challenge, since both functions depend on water management. The system management depends on understanding patterns and regimes. The hydroperiod and hydrodynamics are the dominant driving forces in the formation, evolution and current state of this hydrological system, and influence the biological communities and indicator species. Following the community patterns over time allows tracking of the oscillatory dynamics and possible regime change due to anthropogenic or natural stressors, both as direct observation or by ecological modeling. Understanding the spatial and temporal patterns in the Taim Hydrological System is the basis for the most efficient simultaneous use and conservation

Rubinstein-Taybi syndrome in diverse populations

Rubinstein-Taybi syndrome (RSTS) is an autosomal dominant disorder, caused by loss-of-function variants in CREBBP or EP300. Affected individuals present with distinctive craniofacial features, broad thumbs and/or halluces, and intellectual disability. RSTS phenotype has been well characterized in individuals of European descent but not in other populations. In this study, individuals from diverse populations with RSTS were assessed by clinical examination and facial analysis technology. Clinical data of 38 individuals from 14 different countries were analyzed. The median age was 7 years (age range: 7 months to 47 years), and 63% were females. The most common phenotypic features in all population groups included broad thumbs and/or halluces in 97%, convex nasal ridge in 94%, and arched eyebrows in 92%. Face images of 87 individuals with RSTS (age range: 2 months to 47 years) were collected for evaluation using facial analysis technology. We compared images from 82 individuals with RSTS against 82 age- and sex-matched controls and obtained an area under the receiver operating characteristic curve (AUC) of 0.99 (p < .001), demonstrating excellent discrimination efficacy. The discrimination was, however, poor in the African group (AUC: 0.79; p = .145). Individuals with EP300 variants were more effectively discriminated (AUC: 0.95) compared with those with CREBBP variants (AUC: 0.93). This study shows that clinical examination combined with facial analysis technology may enable earlier and improved diagnosis of RSTS in diverse populations

The TREAT-NMD Duchenne Muscular Dystrophy Registries: Conception, Design, and Utilization by Industry and Academia.

Duchenne muscular dystrophy (DMD) is an X-linked genetic disease, caused by the absence of the dystrophin protein. Although many novel therapies are under development for DMD, there is currently no cure and affected individuals are often confined to a wheelchair by their teens and die in their twenties/thirties. DMD is a rare disease (prevalence &lt;5/10,000). Even the largest countries do not have enough affected patients to rigorously assess novel therapies, unravel genetic complexities, and determine patient outcomes. TREAT-NMD is a worldwide network for neuromuscular diseases that provides an infrastructure to support the delivery of promising new therapies for patients. The harmonized implementation of national and ultimately global patient registries has been central to the success of TREAT-NMD. For the DMD registries within TREAT-NMD, individual countries have chosen to collect patient information in the form of standardized patient registries to increase the overall patient population on which clinical outcomes and new technologies can be assessed. The registries comprise more than 13,500 patients from 31 different countries. Here, we describe how the TREAT-NMD national patient registries for DMD were established. We look at their continued growth and assess how successful they have been at fostering collaboration between academia, patient organizations, and industry