RESUMO
Leri-Weill syndrome (LWS) is a skeletal dysplasia with mesomelic short stature, bilateral Madelung deformity (BMD) and SHOX (short stature homeobox-containing gene) haploinsufficiency. The effect of 24 months of recombinant human growth hormone (rhGH) therapy on the stature and BMD of two females with SHOX haploinsufficiency (demonstrated by fluorescence in situ hybridisation) and LWS was evaluated. Both patients demonstrated an increase in height standard deviation score (SDS) and height velocity SDS over the 24 months of therapy. Patient 1 demonstrated a relative increase in arm-span and upper segment measurements with rhGH while patient 2 demonstrated a relative increase in lower limb length. There was appropriate advancement of bone age, no adverse events and no significant deterioration in BMD. In this study, 24 months of rhGH was a safe and effective therapy for the disproportionate short stature of SHOX haploinsufficiency, with no clinical deterioration of BMD.
Assuntos
Estatura/efeitos dos fármacos , Estatura/genética , Transtornos do Crescimento/tratamento farmacológico , Transtornos do Crescimento/genética , Hormônio do Crescimento/uso terapêutico , Proteínas de Homeodomínio/genética , Adolescente , Braço/anatomia & histologia , Braço/crescimento & desenvolvimento , Osso e Ossos/diagnóstico por imagem , Criança , Feminino , Mãos/diagnóstico por imagem , Haplótipos , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Perna (Membro)/anatomia & histologia , Perna (Membro)/crescimento & desenvolvimento , Masculino , Fenótipo , Radiografia , Proteína de Homoeobox de Baixa EstaturaRESUMO
This study was designed to determine the intrafamilial effect of SHOX haploinsufficiency on stature, by comparing the growth and phenotype of 26 SHOX haploinsufficient individuals with 45 relatives and population standards. It confirmed that SHOX haploinsufficiency leads to growth restriction from birth to final height. Compared to unaffected siblings, the SHOX haploinsufficient cohort was 2.14 SDS (3.8 cm) shorter at birth and 2.1 SDS shorter through childhood. At final height females were 2.4 SDS (14.4 cm) shorter and males 0.8 SDS (5.3 cm) shorter than normal siblings. The family height analysis suggests that the effect of SHOX haploinsufficiency on growth may have been previously underestimated at birth and overestimated in males at final height. SHOX haploinsufficiency leads to short arms in 92%, bilateral Madelung deformity in 73% and short stature in 54%. Females were more severely affected than males. We conclude that SHOX is a major growth gene and that mutations are associated with a broad range of phenotype.
