Unexpected high frequency of skeletal dysplasia in idiopathic short stature and small for gestational age patients

Abstract

Objective: To assess the prevalence of skeletal dysplasias (SDs) in patients with idiopathic short stature (ISS) or small for gestational age (SGA) status. Setting: Rare Endocrine/Growth Diseases Center in Paris, France. Design: A prospective study on consecutive patients with ISS and SGA enrolled from 2004 to 2009. Method: We used a standardized workup to classify patients into well-established diagnostic categories. Of 713 patients with ISS (nZ417) or SGA status (nZ296), 50.9% underwent a skeletal survey. We chose patients labeled normal or with a prepubertal slowdown of growth as a comparison group. Results: Diagnoses were ISS (16.9%), SGA (13.5%), normal growth (24.5%), transient growth rate slowing (17.3%), endocrine dysfunction (12%), genetic syndrome (8.9%), chronic disease (5.1%), and known SD (1.8%). SD was found in 20.9% of SGA and 21.8% ISS patients and in only 13.2% in our comparison group. SD prevalence was significantly higher in the ISS group than in the comparison group, especially (50%) for patients having at least one parent whose height was !K2 SDS. Dyschondrosteosis and hypochondroplasia were the most frequently identified SD, and genetic anomaly was found in 61.5 and 30% respectively. Subtle SD was found equally in the three groups and require long-term growth follow-up to evaluate the impact on final height. Conclusion: SD may explain more than 20% of cases of growth retardation ascribed to ISS or SGA, and this proportion is higher when parental height is !K2 SDS. A skeletal survey should be obtained in patients with delayed growth in a context of ISS or SGA.

Growth throughout childhood of children born growth restricted

“…In the five children with height SDS below target range, we did not investigate other underlying conditions. A concomitant fetal condition that also affects postnatal growth, such as mild skeletal dysplasia or multifactorial disorder38 39 was thus not found, nor previously diagnosed.…”

Characterization of patients with genetic diseases of the skeleton in a Colombian referral center

“…Al revisar otros estudios publicados, los datos de este contrastaron con los reportados por Flechtner, et al, en 2.546 pacientes con talla baja evaluados a lo largo de cinco años, 12 % de los cuales presentaba trastornos endocrinos, 8,9 %, trastornos de etiología genética, 5,1 %, condiciones crónicas, y 5,9 %, displasias óseas (19).…”

“…Los diagnósticos finales con etiología clara de enfermedades genéticas del esqueleto correspondieron a 37,1 % (164 pacientes), distribuidos en 22 de los 40 grupos de la nosología y la clasificación, siendo el más frecuente el 29 (46 pacientes con enfermedades del grupo de componentes esqueléticos con desarrollo desorganizado), seguido por el 30 (36 pacientes con síndromes de crecimiento excesivo y compromiso esquelético), el 27 (17 pacientes con enfermedades de depósito lisosómico y compromiso esquelético), el 25 (11 pacientes con osteogénesis imperfecta u otras enfermedades con disminución de la densidad ósea), y el 4 (10 pacientes con alteraciones de la sulfatación), entre otros, lo cual contrasta ampliamente con el estudio de Flechtner, et al, en el cual se evaluaron pacientes con talla baja idiopática y pequeños para la edad de gestación, entre quienes los grupos preponderantes fueron el 1 (condrodisplasia, FGFR3) y el 17 (displasia mesomélica y rizomesomélica) (19). Es probable que estas diferencias se deban a que, en este estudio, el rango de edad de los pacientes era mayor (0 a 21 años; media de edad: 9,5 años) y las posibilidades de acceso al diagnóstico confirmatorio mediante métodos moleculares también lo eran.…”

Evaluation of the Child with Short Stature

“…10,11 Multiple evaluations over time may be quite valuable, because skeletal dysplasia may be later confirmed in up to 20% of patients previously labeled as idiopathic short stature or small for gestational age. 12 This paper does not focus on these proportionate short stature types because it is extremely rare for such patients to present undiagnosed to the orthopedic surgeon.…”