Acampomelic campomelic dysplasia with SOX9 mutation

Abstract

Campomelic dysplasia (CMPD; MIM 114290) is a rare disorder characterised by a distinctive pattern of abnormal skeletal features and a generally lethal outcome as a result of respiratory distress. Mutations in the SOX9 gene are reported in affected children with CMPD. Acampomelic CMPD is a clinical variant of the more commonly encountered CMPD but is characterised by absence of long bone curvature (acampomelia). We report a one-year-old boy who presented at birth with a flat facial profile with depressed nasal bridge, micrognathia, cleft palate and microstomia; genital findings consisting of bifid scrotum, perineal hypospadias and undescended testes and tracheomalacia. Other abnormalities include a bifid kidney, deep plantar creases and limited elbow extension. Skeletal survey showed typical CMPD changes such as bilateral hypoplastic scapulae, 11 pairs of ribs, delayed bone age but without campomelia. The patient's condition gradually improved over time. Both his parents are well and not related. Genomic analysis showed a de novo heterozygous missense mutation K173E (AAG→GAG; nucleotide position 889) located within the DNA binding HMG (high mobility group) domain of SOX9 gene. We postulated that this mutation is associated with residual activity of SOX9 protein leading to a milder phenotype or acampomelic CMPD.