Fallo de medro en Pediatría de Atención Primaria: recomendaciones para su abordaje y seguimiento / Failure to Thrive in Primary Care pediatrics: recommendations for its approach and follow-up

El fallo de medro representa la dificultad para mantener un ritmo de crecimiento adecuado, tanto en peso como en talla, en menores de tres años. Se trata de una entidad actualmente infradiagnosticada que puede repercutir en el desarrollo físico, intelectual, emocional y social de los niños. El pediatra de Atención Primaria es clave en la identificación precoz y en la prevención de su morbilidad. Este documento representa una herramienta útil para el desarrollo de la labor conjunta del pediatra y la enfermería pediátrica, realizando una intervención precoz, individualizada y eficiente en estos niños. (AU)

Failure to thrive is poor physical growth, both in weight and height, in children under three years of age. This underdiagnosed entity can affect children’s physical, intellectual, emotional and social development. Paediatric Primary Care is crucial in early diagnosis and prevention of their morbidity. This document represents a useful tool for the teamwork between paediatricians and paediatric nursing. Its objective is to carry out an early, individualized and efficient approach in these children. (AU)

Longitudinal study of the newborn small for gestational age. Growth recovery and conditioning factors.

Introduction: Background: small-for-gestational-age (SGA) newborns present a higher morbidity and mortality rate when compared to infants born appropriate for gestational age (AGA), as well as insufficient growth, with height far from their target and in some cases a low final height (< -2 SDs). Objective: the aim of this study was to determine when catch-up growth (CUG) in height occurs in these children, and which factors are associated with lack of CUG. Material and methods: this is a retrospective study of SGAs born between 2011 and 2015 in a secondary hospital. Anthropometric measurements were taken consecutively until CUG was reached, and fetal, placental, parental, newborn, and postnatal variables were studied. Results: a total of 358 SGAs were included from a total of 5,585 live newborns. At 6 and 48 months of life, 93.6 % and 96.4 % of SGAs achieved CUG, respectively. By subgroups, symmetric SGAs performed worse than asymmetric SGAs with CUG in 84 % and 92 % at 6 and 48 months of life, respectively. The same occurred in the subgroup of preterm SGAs with respect to term SGAs, with worse CUGs of 88.2 % and 91.2 % at 6 and 48 months of life, respectively. Prematurity, symmetrical SGA, intrauterine growth retardation (IUGR), preeclampsia, previous child SGA, perinatal morbidity, and comorbidity during follow-up were associated with absence of CUG. Conclusions: the majority of SGAs had CUG in the first months of life. The worst outcomes were for preterm and symmetric SGAs.

Introducción: Antecedentes: el recién nacido pequeño para la edad gestacional (PEG) presenta mayor morbimortalidad que el recién nacido con peso adecuado (PAEG), así como un crecimiento insuficiente con talla alejada de la talla diana y, en algunos casos, talla final baja (< -2 DE). Objetivo: el objetivo de este estudio fue determinar en qué momento se produce el crecimiento compensador (CUG) de la talla en estos niños y conocer qué factores se asocian a la falta de dicho crecimiento compensador. Material y métodos: estudio retrospectivo de los recién nacidos PEG entre los años 2011 y 2015 en un hospital secundario. Se tomaron medidas antropométricas de forma consecutiva hasta alcanzar el CUG y se estudiaron las variables fetales, placentarias, parentales, neonatales y posnatales. Resultados: se incluyeron 358 PEG de un total de 5585 recién nacidos vivos. A los 6 y 48 meses de vida alcanzaron el CUG el 93,6 % y 96,4 % de los PEG, respectivamente. Por subgrupos, los PEG simétricos obtuvieron peores resultados que los PEG asimétricos, con CUG del 84 % y 92 % a los 6 y 48 meses de vida, respectivamente. Lo mismo ocurrió en el subgrupo de PEG prematuros respecto de los PEG a término, con CUG peores del 88,2 % y 91,2 % a los 6 y 48 meses de vida, respectivamente. La prematuridad, el PEG simétrico, la restricción del crecimiento intrauterino, la preeclampsia, tener un hijo previo PEG, la morbilidad perinatal y la comorbilidad durante el seguimiento se asociaron a la ausencia de CUG. Conclusiones: la mayoría de los PEG alcanzaron el CUG en los primeros meses de vida. Los peores resultados fueron para los PEG prematuros y simétricos.

High prevalence of variants in skeletal dysplasia associated genes in individuals with short stature and minor skeletal anomalies.

OBJECTIVE: Next generation sequencing (NGS) has expanded the diagnostic paradigm turning the focus to the growth plate. The aim of the study was to determine the prevalence of variants in genes implicated in skeletal dysplasias in probands with short stature and mild skeletal anomalies. DESIGN: Clinical and radiological data were collected from 108 probands with short stature and mild skeletal anomalies. METHODS: A customized skeletal dysplasia NGS panel was performed. Variants were classified using ACMG recommendations and Sherloc. Anthropometric measurements and skeletal anomalies were subsequently compared in those with or without an identified genetic defect. RESULTS: Heterozygous variants were identified in 21/108 probands (19.4%). Variants were most frequently identified in ACAN (n = 10) and IHH (n = 7) whilst one variant was detected in COL2A1, CREBBP, EXT1, and PTPN11. Statistically significant differences (P < 0.05) were observed for sitting height/height (SH/H) ratio, SH/H ratio standard deviation score (SDS), and the SH/H ratio SDS >1 in those with an identified variant compared to those without. CONCLUSIONS: A molecular defect was elucidated in a fifth of patients. Thus, the prevalence of mild forms of skeletal dysplasias is relatively high in individuals with short stature and mild skeletal anomalies, with variants in ACAN and IHH accounting for 81% of the cases. An elevated SH/H ratio appears to be associated with a greater probability in detecting a variant, but no other clinical or radiological feature has been found determinant to finding a genetic cause. Currently, we cannot perform extensive molecular studies in all short stature individuals so detailed clinical and radiological phenotyping may orientate which are the candidate patients to obtain worthwhile results. In addition, detailed phenotyping of probands and family members will often aid variant classification.

Mutations in C-natriuretic peptide (NPPC): a novel cause of autosomal dominant short stature.

PurposeC-type natriuretic peptide (CNP) and its principal receptor, natriuretic peptide receptor B (NPR-B), have been shown to be important in skeletal development. CNP and NPR-B are encoded by natriuretic peptide precursor-C (NPPC) and natriuretic peptide receptor 2 (NPR2) genes, respectively. While NPR2 mutations have been described in patients with skeletal dysplasias and idiopathic short stature (ISS), and several Npr2 and Nppc skeletal dysplasia mouse models exist, no mutations in NPPC have been described in patients to date.MethodsNPPC was screened in 668 patients (357 with disproportionate short stature and 311 with autosomal dominant ISS) and 29 additional ISS families in an ongoing whole-exome sequencing study.ResultsTwo heterozygous NPPC mutations, located in the highly conserved CNP ring, were identified. Both showed significant reductions in cyclic guanosine monophosphate synthesis, confirming their pathogenicity. Interestingly, one has been previously linked to skeletal abnormalities in the spontaneous Nppc mouse long-bone abnormality (lbab) mutant.ConclusionsOur results demonstrate, for the first time, that NPPC mutations cause autosomal dominant short stature in humans. The NPPC mutations cosegregated with a short stature and small hands phenotype. A CNP analog, which is currently in clinical trials for the treatment of achondroplasia, seems a promising therapeutic approach, since it directly replaces the defective protein.

Osteoporosis y deformidades óseas: sospecha de síndrome de Winchester / Osteoporosis and skeletal deformities; suspicion of Winchester syndrome

Los síndromes de osteólisis hereditaria se caracterizan por destrucción esquelética debida a una incontrolada resorción ósea. Constituyen un grupo heterogéneo de entidades infrecuentes de clasificación aún discutida, en la que se incluyen formas multicéntricas carpotarsales: síndromes de Winchester, de nodulosis-artropatía-osteólisis (NAO) y de Torg, de herencia autosómica recesiva. Se presenta el caso de un niño de13 años y origen marroquí, con incapacidad para la bipedestación y la manipulación por deformidad progresiva de las manos y los pies, así como fracturas patológicas ante mínimos traumatismos. Radiológicamente faltan carpo y tarso, y hay fracturas en las extremidades y osteoporosis intensa, sin alteraciones en el metabolismo fosfocálcico. Presenta alteraciones corneales y agudeza visual muy disminuida. Su único hermano tiene los mismos síntomas; sus padres son primos y están sanos. Ante tales hallazgos, se establece el síndrome de Winchester como diagnóstico más probable (AU)

Hereditary osteolysis syndromes are characterized by the destruction of skeletal groups produced by uncontrolled bone resorption. These syndromes constitute aheterogeneous group of infrequent entities. The classification of these entities is still controversial and includes the following multicentric carpal-tarsal forms: Winchester, NAO (nodulosis-arthropathyosteolysis) and Torg syndromes, all of which show autosomal recessive inheritance. We present a 13-year-old boy of Moroccan origin with impaired walking and hand function due to progressive deformity of the hands and feet, as well aspathological fractures after minimal trauma. Radiographic examination revealed dissolution of carpal and tarsal bones, fractures in the extremities and intense osteoporosis, without alterations inphosphocalcic metabolism. The patient had corneous alterations and highly diminished visual keenness. The boy’s only brother showed the same symptoms but his parents and cousins were healthy. Based on the findings in our patient, Winchester syndrome was established as the most probable diagnosis (AU)