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The transforming growth factor ß (TGF-ß) and bone morphogenetic protein (BMP) signaling pathways play a pivotal role in bone development and skeletal health. More than 30 different types of skeletal dysplasia are now known to be caused by pathogenic variants in genes that belong to the TGF-ß superfamily and/or regulate TGF-ß/BMP bioavailability. This review describes the latest advances in skeletal dysplasia that is due to impaired TGF-ß/BMP signaling and results in short stature (acromelic dysplasia and cardiospondylocarpofacial syndrome) or tall stature (Marfan syndrome). We thoroughly describe the clinical features of the patients, the underlying genetic findings, and the pathomolecular mechanisms leading to disease, which have been investigated mainly using patient-derived skin fibroblasts and mouse models. Although no pharmacological treatment is yet available for skeletal dysplasia due to impaired TGF-ß/BMP signaling, in recent years advances in the use of drugs targeting TGF-ß have been made, and we also discuss these advances.
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Osteocondrodisplasias , Osteosclerosis , Animales , Ratones , Disponibilidad Biológica , Desarrollo Óseo , Factor de Crecimiento Transformador beta/genéticaRESUMEN
ERI1 is a 3'-to-5' exoribonuclease involved in RNA metabolic pathways including 5.8S rRNA processing and turnover of histone mRNAs. Its biological and medical significance remain unclear. Here, we uncover a phenotypic dichotomy associated with bi-allelic ERI1 variants by reporting eight affected individuals from seven unrelated families. A severe spondyloepimetaphyseal dysplasia (SEMD) was identified in five affected individuals with missense variants but not in those with bi-allelic null variants, who showed mild intellectual disability and digital anomalies. The ERI1 missense variants cause a loss of the exoribonuclease activity, leading to defective trimming of the 5.8S rRNA 3' end and a decreased degradation of replication-dependent histone mRNAs. Affected-individual-derived induced pluripotent stem cells (iPSCs) showed impaired in vitro chondrogenesis with downregulation of genes regulating skeletal patterning. Our study establishes an entity previously unreported in OMIM and provides a model showing a more severe effect of missense alleles than null alleles within recessive genotypes, suggesting a key role of ERI1-mediated RNA metabolism in human skeletal patterning and chondrogenesis.
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Exorribonucleasas , Histonas , Humanos , Exorribonucleasas/genética , Histonas/genética , Mutación Missense/genética , ARN Ribosómico 5.8S , ARN , ARN Mensajero/genéticaRESUMEN
Linear growth during three distinct stages of life determines attained stature in adulthood: namely, in utero, early postnatal life, and puberty and the adolescent period. Individual host factors, genetics, and the environment, including nutrition, influence attained human stature. Each period of physical growth has its specific biological and environmental considerations. Recent epidemiologic investigations reveal a strong influence of prenatal factors on linear size at birth that in turn influence the postnatal growth trajectory. Although average population height changes have been documented in high-income regions, stature as a complex human trait is not well understood or easily modified. This review summarizes the biology of linear growth and its major drivers, including nutrition from a life-course perspective, the genetics of programmed growth patterns or height, and gene-environment interactions that determine human stature in toto over the life span. Implications for public health interventions and knowledge gaps are discussed.
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Estatura , Interacción Gen-Ambiente , Humanos , Estado Nutricional , Femenino , Ambiente , Embarazo , AdolescenteRESUMEN
Human culture, biology, and health were shaped dramatically by the onset of agriculture â¼12,000 y B.P. This shift is hypothesized to have resulted in increased individual fitness and population growth as evidenced by archaeological and population genomic data alongside a decline in physiological health as inferred from skeletal remains. Here, we consider osteological and ancient DNA data from the same prehistoric individuals to study human stature variation as a proxy for health across a transition to agriculture. Specifically, we compared "predicted" genetic contributions to height from paleogenomic data and "achieved" adult osteological height estimated from long bone measurements for 167 individuals across Europe spanning the Upper Paleolithic to Iron Age (â¼38,000 to 2,400 B.P.). We found that individuals from the Neolithic were shorter than expected (given their individual polygenic height scores) by an average of −3.82 cm relative to individuals from the Upper Paleolithic and Mesolithic (P = 0.040) and −2.21 cm shorter relative to post-Neolithic individuals (P = 0.068), with osteological vs. expected stature steadily increasing across the Copper (+1.95 cm relative to the Neolithic), Bronze (+2.70 cm), and Iron (+3.27 cm) Ages. These results were attenuated when we additionally accounted for genome-wide genetic ancestry variation: for example, with Neolithic individuals −2.82 cm shorter than expected on average relative to pre-Neolithic individuals (P = 0.120). We also incorporated observations of paleopathological indicators of nonspecific stress that can persist from childhood to adulthood in skeletal remains into our model. Overall, our work highlights the potential of integrating disparate datasets to explore proxies of health in prehistory.
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Agricultura , Estatura , Agricultores , Salud , Esqueleto , Adulto , Agricultura/historia , Estatura/genética , Niño , ADN Antiguo , Europa (Continente) , Agricultores/historia , Variación Genética , Genómica , Salud/historia , Historia Antigua , Humanos , Paleopatología , Esqueleto/anatomía & histologíaRESUMEN
Latent transforming growth factor ß (TGFß)-binding proteins (LTBPs) are microfibril-associated proteins essential for anchoring TGFß in the extracellular matrix (ECM) as well as for correct assembly of ECM components. Variants in LTBP2, LTBP3, and LTBP4 have been identified in several autosomal recessive Mendelian disorders with skeletal abnormalities with or without impaired development of elastin-rich tissues. Thus far, the human phenotype associated with LTBP1 deficiency has remained enigmatic. In this study, we report homozygous premature truncating LTBP1 variants in eight affected individuals from four unrelated consanguineous families. Affected individuals present with connective tissue features (cutis laxa and inguinal hernia), craniofacial dysmorphology, variable heart defects, and prominent skeletal features (craniosynostosis, short stature, brachydactyly, and syndactyly). In vitro studies on proband-derived dermal fibroblasts indicate distinct molecular mechanisms depending on the position of the variant in LTBP1. C-terminal variants lead to an altered LTBP1 loosely anchored in the microfibrillar network and cause increased ECM deposition in cultured fibroblasts associated with excessive TGFß growth factor activation and signaling. In contrast, N-terminal truncation results in a loss of LTBP1 that does not alter TGFß levels or ECM assembly. In vivo validation with two independent zebrafish lines carrying mutations in ltbp1 induce abnormal collagen fibrillogenesis in skin and intervertebral ligaments and ectopic bone formation on the vertebrae. In addition, one of the mutant zebrafish lines shows voluminous and hypo-mineralized vertebrae. Overall, our findings in humans and zebrafish show that LTBP1 function is crucial for skin and bone ECM assembly and homeostasis.
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Colágeno/metabolismo , Cutis Laxo/etiología , Variación Genética , Proteínas de Unión a TGF-beta Latente/genética , Adolescente , Alelos , Animales , Células Cultivadas , Niño , Preescolar , Cutis Laxo/patología , Matriz Extracelular/metabolismo , Femenino , Fibroblastos/metabolismo , Fibroblastos/patología , Humanos , Lactante , Masculino , Linaje , Piel/metabolismo , Piel/patología , Pez CebraRESUMEN
OBJECTIVE: To evaluate the presence of multiple genetic diagnoses in syndromic growth disorders. STUDY DESIGN: We carried out a cross-sectional study to evaluate 115 patients with syndromic tall (n = 24) or short stature (n = 91) of unknown cause from a tertiary referral center for growth disorders. Exome sequencing was performed to assess germline single nucleotide, InDel, and copy number variants. All variants were classified according to ACMG/AMP guidelines. The main outcome measured was the frequency of multiple genetic diagnoses in a cohort of children with syndromic growth disorders. RESULTS: The total diagnostic yield of the cohort was 54.8% (63/115). Six patients had multiple genetic diagnoses (tall stature group = 2; short stature group = 4). The proportion of multiple diagnoses within total cases was 5.2% (6/115), and within solved cases was 9.5% (6/63). No characteristics were significantly more frequent when compared with patients with single or multiple genetic findings. Among patients with multiple diagnoses, 3 had syndromes with overlapping clinical features, and the others had syndromes with distinct phenotypes. CONCLUSION: Recognition of multiple genetic diagnoses as a possibility in complex cases of syndromic growth disorders opens a new perspective on treatment and genetic counseling for affected patients, defying the medical common sense of trying to fit all findings into one diagnosis.
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Enanismo , Trastornos del Crecimiento , Niño , Femenino , Humanos , Secuenciación del Exoma , Estudios Transversales , Trastornos del Crecimiento/diagnóstico , Trastornos del Crecimiento/genética , Enanismo/genética , FenotipoRESUMEN
Skeletal dysplasias are a heterogeneous group of disorders presenting mild to lethal defects. Several factors, such as genetic, prenatal, and postnatal environmental may contribute to reduced growth. Fourteen families of Pakistani origin, presenting the syndromic form of short stature either in the autosomal recessive or autosomal dominant manner were clinically and genetically investigated to uncover the underlying genetic etiology. Homozygosity mapping, whole exome sequencing, and Sanger sequencing were used to search for the disease-causing gene variants. In total, we have identified 13 sequence variants in 10 different genes. The variants in the HSPG2 and XRCC4 genes were not reported previously in the Pakistani population. This study will expand the mutation spectrum of the identified genes and will help in improved diagnosis of the syndromic form of short stature in the local population.
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Enanismo , Secuenciación del Exoma , Mutación , Linaje , Humanos , Femenino , Masculino , Enanismo/genética , Niño , Pakistán/epidemiología , Predisposición Genética a la Enfermedad , Homocigoto , Fenotipo , Síndrome , Preescolar , Adolescente , Estudios de Asociación GenéticaRESUMEN
This is a retrospective chart and radiographic review of 145 patients who underwent full-body EOS imaging; 109 males and 36 females. The mean ages of the female and male subsets are 28.8 (SD = 11.6) years and 29.5 (SD = 11.8) years, respectively. The sum of the foot height (Ft) and the tibial length (T) for each subject was compared to their femur length (Fe). Subsequently, the sum of the tibial (T) and femoral lengths (Fe) were compared to their respective upper body lengths (UB), as measured from the tops of the femoral heads. A linear regression test was performed to determine whether a Lucas sequence-based relationship exists between Ft + T and Fe, and between T + Fe and UB. The regression for the relationship between Ft + T and Fe for the entire cohort (R = 0.82, R2 = 0.70), the female subset (R = 0.94, R2 = 0.88) and the male subset (R = 0.75, R2 = 0.57), all demonstrated a strong positive correlation between Ft + T and Fe and showed that Ft + T is a likely predictor of Fe. The regression test for the entire cohort demonstrated a moderately positive correlation between T + Fe and UB (R = 0.41, R2 = 0.17, F(1, 145) = 29.42, p = 2.4E-07). A stronger correlation was found for the relationship between T + Fe and UB (R = 0.57, R2 = 0.32, F(1, 35) = 16.64, p = 2.5E-05) for the female subset relative to the male subset (R = 0.20, R2 = 0.038, F(1, 35) = 4.37, p = 0.04). There appears to be a Lucas sequence relationship between the lengths of the foot height, tibial length, femoral length and upper body length, which together make up standing height. This mathematical proportion relationship is stronger in females than males.
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Pie , Extremidad Inferior , Humanos , Masculino , Femenino , Adulto , Estudios Retrospectivos , Tibia/diagnóstico por imagen , Fémur/diagnóstico por imagenRESUMEN
SOFT syndrome (Short stature-Onychodysplasia-Facial dysmorphism-hypoTrichosis) is a rare primordial dwarfism syndrome caused by biallelic variants in POC1A encoding a centriolar protein. To refine the phenotypic spectrum of SOFT syndrome, recently shown to include metabolic features, we conducted a systematic review of all published cases (19 studies, including 42 patients). The SOFT tetrad affected only 24 patients (57%), while all cases presented with short stature from birth (median height: -5.5SDS([-8.5]-[-2.8])/adult height: 132.5 cm(103.5-148)), which was most often disproportionate (90.5%), with relative macrocephaly. Bone involvement resulted in short hands and feet (100%), brachydactyly (92.5%), metaphyseal (92%) or epiphyseal (84%) anomalies, and/or sacrum/pelvis hypoplasia (58%). Serum IGF-I was increased (median IGF-I level: + 2 SDS ([-0.5]-[+ 3])). Recombinant human growth hormone (rhGH) therapy was stopped for absence/poor growth response (7/9 patients, 78%) and/or hyperglycemia (4/9 patients, 45%). Among 11 patients evaluated, 10 (91%) presented with central distribution of fat (73%), clinical (64%) and/or biological insulin resistance (IR) (100%, median HOMA-IR: 18), dyslipidemia (80%), and hepatic steatosis (100%). Glucose tolerance abnormalities affected 58% of patients aged over 10 years. Patients harbored biallelic missense (52.4%) or truncating (45.2%) POC1A variants. Biallelic null variants, affecting 36% of patients, were less frequently associated with the SOFT tetrad (33% vs 70% respectively, p = 0.027) as compared to other variants, without difference in the prevalence of metabolic abnormalities. POC1A should be sequenced in children with short stature, altered glucose/insulin homeostasis and/or centripetal fat distribution. In patients with SOFT syndrome, rhGH treatment is not indicated, and IR-related complications should be regularly screened and monitored.PROSPERO registration: CRD42023460876.
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A minority of children born small for gestational age (SGA) may experience catch-up growth failure and remain short in adulthood. However, the underlying causes and mechanisms of this phenomenon are not yet fully comprehended. We reviewed the present state of research concerning the growth hormone-insulin-like growth factor axis and growth plate in SGA children who fail to achieve catch-up growth. Additionally, we explored the factors influencing catch-up growth in SGA children and potential molecular mechanisms involved. Furthermore, we considered the potential benefits of supplementary nutrition, specific dietary patterns, probiotics and drug therapy in facilitating catch-up growth.
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Recién Nacido Pequeño para la Edad Gestacional , Humanos , Recién Nacido Pequeño para la Edad Gestacional/crecimiento & desarrollo , Recién Nacido , Niño , Trastornos del Crecimiento , Hormona de Crecimiento Humana , Desarrollo Infantil/fisiologíaRESUMEN
BACKGROUND: Height loss in aging has been recognized to reflect a decline in musculoskeletal health but not investigated in relation to dietary factors, such as sugar-sweetened beverages (SSBs), the consumption of which may deteriorate musculoskeletal health. OBJECTIVES: This study aimed to evaluate the longitudinal association of habitual consumption of total SSBs and its subtypes with height loss and examine effect-modification by age, sex, and anthropometry. METHODS: We evaluated 16,230 adults aged 40-79 y in the European Prospective Investigation into Cancer and Nutrition-Norfolk cohort. At baseline (1993-1997), SSB consumption (soft drinks, squashes, sweetened milk beverages, sweetened coffee/tea, and sweetened alcoholic beverages) was assessed using 7-d food diaries. Height was objectively measured at the baseline, second (1997-2000), and third (2004-2011) health checks. Multivariable linear regression was used to examine baseline SSB consumption and the rate of height change over the follow-up. RESULTS: The median (IQR) height change was -1.07 (-2.09 to -0.28) cm/10 y. Adjusted for potential confounders including behavioral factors, medications, and baseline body mass index (BMI), total SSB consumption was associated with height loss (ß: -0.024; 95% CI: -0.046, -0.001 cm/10 y per 250 g/d of SSB), and similar results were seen for the individual beverages, except for sweetened milk beverages (ß: +0.07; 95% CI: -0.16, 0.30), with wide CIs. No effect-modification by prespecified factors was evident, except for baseline BMI (P-interaction = 0.037). Total SSB consumption was associated with height loss (-0.038; 95% CI: -0.073, -0.004) in participants with BMI ≤ 25 kg/m2 but not apparently in those with BMI > 25 kg/m2. CONCLUSIONS: SSB consumption was modestly associated with height loss, particularly in adults with normal weight status.
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Estatura , Bebidas Azucaradas , Humanos , Persona de Mediana Edad , Masculino , Femenino , Bebidas Azucaradas/efectos adversos , Adulto , Estudios Longitudinales , Anciano , Estudios Prospectivos , Índice de Masa Corporal , Registros de Dieta , DietaRESUMEN
Spondyloocular syndrome (SOS) is a rare autosomal recessive skeletal and ocular disorder with variable phenotypes. It is caused by pathogenic mutation in the XYLT2 gene, which encodes the enzyme xylo-transferase, necessary for the synthesis of proteoglycan. It is characterized by generalized osteoporosis, short stature, hearing impairment, eye abnormalities, and cardiac defects. Till date only 24 cases have been reported worldwide with no cases documented from India. We subjected the patient to relevant biochemical investigations and Dual Energy X-ray Absorptiometry (DEXA) scan along with Next Generation Clinical Exome Sequencing (NGCES). We report a case of 23-year-old male who presented with recurrent long bone fractures, congenital heart defects, eye abnormalities (bilateral corneal opacities and atrophic bulbi), and short stature. In addition, our patient also had genu valgum and right-sided hydrocele which have never been reported in SOS till date. On genetic analysis, NGCES revealed a novel pathogenic frameshift variant c.191_192 delCA, p.(Thr64fs*22) in the XYLT2 gene. The patient is doing well on six monthly zoledronic acid infusions.
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Mutación , Fenotipo , Humanos , Masculino , Adulto Joven , India , Mutación/genética , Pentosiltransferasa/genética , AdultoRESUMEN
Although fractures are the defining characteristic of osteogenesis imperfecta (OI), the disorder affects many tissues. Here we discuss three facets of the OI phenotype, skeletal growth and development, skeletal muscle weakness and the dental and craniofacial characteristics. Short stature is almost universal in the more severe forms of OI and is probably caused by a combination of direct effects of the underlying genetic defect on growth plates and indirect effects of fractures, bone deformities and scoliosis. Recent studies have developed OI type-specific growth curves, which allow determining whether a given child with OI grows as expected for OI type. Impaired muscle function is an important OI-related phenotype in severe OI. Muscles may be directly affected in OI by collagen type I abnormalities in muscle connective tissue and in the muscle-tendon unit. Indirect effects like bone deformities and lack of physical activity may also contribute to low muscle mass and function. Dental and craniofacial abnormalities are also very common in severe OI and include abnormal tooth structure (dentinogenesis imperfecta), malocclusion, and deformities in the bones of the face and the skull. It is hoped that future treatment approaches will address these OI-related phenotypes.
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Biallelic pathogenic variants in RMRP, the gene encoding the RNA component of RNase mitochondrial RNA processing enzyme complex, have been reported in individuals with cartilage hair hypoplasia (CHH). CHH is prevalent in Finnish and Amish populations due to a founder pathogenic variant, n.71A > G. Based on the manifestations in the Finnish and Amish individuals, the hallmarks of CHH are prenatal-onset growth failure, metaphyseal dysplasia, hair hypoplasia, immunodeficiency, and other extraskeletal manifestations. Herein, we report six Japanese individuals with CHH from four families. All probands presented with moderate short stature with mild metaphyseal dysplasia or brachydactyly. One of them had hair hypoplasia and the other immunodeficiency. By contrast, the affected siblings of two families showed only mild short stature. We also reviewed all previously reported 13 Japanese individuals. No n.71A > G allele was detected. The proportions of Japanese versus Finnish individuals were 0% versus 70% for birth length < -2.0 SD, 84% versus 100% for metaphyseal dysplasia and 26% versus 88% for hair hypoplasia. Milder manifestations in the Japanese individuals may be related to the difference of genotypes. The mildest form of CHH phenotypes is mild short stature without overt skeletal alteration or extraskeletal manifestation and can be termed "RMRP-related short stature".
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Cabello , Osteocondrodisplasias , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Alelos , Enanismo/genética , Enanismo/patología , Pueblos del Este de Asia , Genotipo , Cabello/anomalías , Cabello/patología , Enfermedad de Hirschsprung/genética , Enfermedad de Hirschsprung/patología , Enfermedad de Hirschsprung/diagnóstico , Japón/epidemiología , Mutación/genética , Osteocondrodisplasias/genética , Osteocondrodisplasias/patología , Osteocondrodisplasias/congénito , Linaje , Fenotipo , Enfermedades de Inmunodeficiencia Primaria/genética , Enfermedades de Inmunodeficiencia Primaria/patología , ARN Largo no Codificante/genéticaRESUMEN
Bardet-Biedl syndrome (BBS) is an inherited ciliopathy affecting multiple organs and systems with wide clinical and genetic heterogeneity. To date, biallelic variants of the LZTFL1 gene have been reported only in six patients with BBS. We identified a homozygous LZTFL1 nonsense variant in a boy presenting with classical BBS features. In addition, he showed a more pronounced cognitive impairment than previously reported subjects and severe short stature, matching the phenotype displayed by some other patients with LZTFL1 variants and lztfl1 knock-out mice. This case report contributes to a better understanding of the clinical spectrum associated with LZTFL1 pathogenic variants, and highlights possible genotype-phenotype correlations.
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CHST3-related chondrodysplasia with congenital joint dislocations (CDCJD, #MIM 143095), is a rare genetic skeletal disorder caused by biallelic loss of function variants in CHST3. CHST3 is critical for the sulfation of chondroitin sulfate. This study delineates the clinical presentation of nine individuals featuring the key symptoms of CDCJD; congenital joint (knee and elbow) dislocations, short trunk short stature progressive vertebral anomalies, and metacarpal shortening. Additional manifestations include irregular distal femoral epiphysis, supernumerary carpal ossification centers, bifid humerus, club foot, and cardiac abnormalities. Sanger sequencing was carried out to investigate molecular etiology in eight patients and exome sequencing in one. Genetic testing revealed five homozygous variants in CHST3 (four were novel and one was previously reported). All these variants are located on sulfotransferase domain of CHST3 protein and were classified as pathogenic/ likely pathogenic. We thus report on nine individuals with CHST3-related chondrodysplasia with congenital joint dislocations from India and suggest monitoring the health of cardiac valves in this condition.
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Enanismo , Luxaciones Articulares , Anomalías Musculoesqueléticas , Osteocondrodisplasias , Humanos , Luxaciones Articulares/diagnóstico , Luxaciones Articulares/genética , Mutación , Osteocondrodisplasias/diagnóstico , Osteocondrodisplasias/genética , Sulfotransferasas/genéticaRESUMEN
Aplasia Cutis Congenita with Ectrodactyly Skeletal Syndrome (ACCES, OMIM #619959) is an extremely rare multiple congenital anomalies syndrome caused by haploinsufficiency of the UBA2 gene. This syndrome presents with growth retardation, dysmorphic facial features, neurodevelopmental delay, skeletal problems including ectrodactyly, developmental dysplasia of the hip (DDH) and scoliosis, skin findings such as aplasia cutis, and some internal organ abnormalities. Our 13-year-old female patient and her 38-year-old father had a skeletal dysplasia phenotype with disproportionate short stature, bilateral DDH, mild epiphyseal involvement, scoliosis, and increased lumbar lordosis. Both were neurodevelopmentally normal and had mild dysmorphic facial features and mild ectodermal findings. The dominant inheritance pattern in the pedigree suggested a pre-diagnosis of spondyloepiphyseal dysplasia tarda. The exome sequencing analysis of the patient has identified a novel heterozygous variant, NM_005499.2:c.460-2A >G, in the UBA2 gene, and the father was found heterozygous either. The isolated spondyloepiphyseal involvement of our patients was an unusual presentation compared to patients with ACCES syndrome previously reported in the literature. Considering the highly variable expressiveness of ACCES syndrome and the co-occurrence of familial hip dysplasia and vertebral problems, we suggest that this syndrome can also be classified under "Spondyloepi(meta)physial dysplasia (SE(M)D)" in the nosology of genetic skeletal disorders.
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Childhood stunting and wasting, or decreased linear and ponderal growth associated with undernutrition, continue to be a major global public health challenge. Although many of the current therapeutic and dietary interventions have significantly reduced childhood mortality caused by undernutrition, there remain great inefficacies in improving childhood stunting. Longitudinal bone growth in children is governed by different genetic, nutritional and other environmental factors acting systemically on the endocrine system and locally at the growth plate. Recent studies have shown that this intricate interplay between nutritional and hormonal regulation of the growth plate could involve the gut microbiota, highlighting the importance of a holistic approach in tackling childhood undernutrition. In this review, I focus on the mechanistic insights provided by these recent advances in gut microbiota research and discuss ongoing development of microbiota-based therapeutics in humans, which could be the missing link in solving undernutrition and childhood stunting.
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Desarrollo Óseo , Microbioma Gastrointestinal , Trastornos del Crecimiento , Humanos , Microbioma Gastrointestinal/fisiología , Desarrollo Óseo/fisiología , Niño , Trastornos del Crecimiento/microbiología , Trastornos del Crecimiento/fisiopatología , Animales , Desnutrición/microbiología , Desnutrición/fisiopatología , Desarrollo Infantil/fisiologíaRESUMEN
This study verified the diagnostic accuracy of the nutritional status classified by the international height and BMI references of the World Health Organization (WHO) (WHO/2007), International Obesity Task Force (IOTF/2012) and MULT (2023). The data pool was composed by 22 737 subjects aged five to 16 years from the Santos and Porto Alegre surveys. A correlation matrix between the z-scores of the BMI references and the skinfold measurements was calculated through the Pearson correlation coefficient (r), and the subject's nutritional status was classified according to the international growth references. The accuracy for diagnosing obesity was performed separately by sex and using the 95th percentile of the triceps and subscapular skinfold sum, while Lin's concordance coefficient, Bland-Altman method and the Cohen's Kappa coefficient (Kappa) were used to verify the concordance and reliability among the BMI references. The correlation matrix showed a high positive correlation among the BMI z-scores (r ≥ 0·99) and among the skinfold measurements (r ≥ 0·86). The prevalence of stunting was higher when applying the MULT reference (3·4 %) compared with the WHO reference (2·3 %). The Bland-Altman plots showed the lowest critical difference (CD) between the height references of WHO and MULT (CD = 0·22). Among the BMI references, the WHO obesity percentile presented lower performance than MULT for boys, presenting a lower +LR value (WHO = 6·99/MULT 18 years = 10·99; 19 years = 8·99; 20 years = 8·09) for the same -LR values (0·04). Therefore, MULT reference holds promise as a valuable tool for diagnosing childhood obesity, particularly when considering sex differences. This enhances its suitability for assessing the nutritional status of Brazilian schoolchildren.
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Adiposidad , Estatura , Índice de Masa Corporal , Estado Nutricional , Humanos , Niño , Brasil/epidemiología , Masculino , Femenino , Adolescente , Preescolar , Organización Mundial de la Salud , Valores de Referencia , Obesidad Infantil/epidemiología , Obesidad Infantil/diagnóstico , Reproducibilidad de los Resultados , Grosor de los Pliegues Cutáneos , Prevalencia , Trastornos del Crecimiento/epidemiología , Trastornos del Crecimiento/diagnóstico , Estudios TransversalesRESUMEN
PURPOSE: Vitamin A is related to concentrations of insulin-like growth factor type 1, a protein produced in response to growth hormone, and to increased mobilization of body iron stores. Thus, vitamin A aids in increased hematopoiesis and may be useful in preventing stunting and anemia. This study aimed to identify the association between vitamin A supplementation from the National Vitamin A Supplementation Program instituted in Brazil and stunting and anemia in socially vulnerable Brazilian children. METHODS: This is a Cross-sectional population-based study. Children aged 6-59 months old, living in favelas of a capital city in the Northeast of Brazil, were included. Sociodemographic variables were collected. Vitamin A supplementation was also evaluated using the child's vaccination card information. Anthropometric and capillary hemoglobin evaluations were performed to identify the presence of stunting and anemia, respectively. The association analysis was performed using Poisson regression with robust variance estimation. RESULTS: 598 children participated in this study; 11.3% and 55.6% had stunting and anemia, respectively. As for vitamin A supplementation, 59.5% had taken at least one dose of the supplement,and 3.5% were on the complete supplementation scheme. In the adjusted association analysis, vitamin A supplementation decreased the likelihood of children having stunting and anemia by 8% (RP:0.86; 95% IC 0.86-0.98; p = 0.014) and 31% (RP:0.69; 95% IC 0.53-0.89; p = 0.004), respectively. Children who were fully supplemented were 58% (RP:0.42; 95% IC 0.24-0.77; p = 0.008) less likely to have anemia. CONCLUSION: Thus, vitamin A supplementation is a protective tool against stunting and anemia in children living in a situation of social vulnerability.