Acromesomelic dysplasia, Maroteaux type (AMDM)

Acromesomelic dysplasia, Maroteaux type

Acromesomelic dysplasia, Maroteaux type (AMDM; MIM 602875) is an autosomal recessive skeletal dysplasia caused by loss of function mutations in the natriuretic peptide receptor B gene (NPR2).  Birth length and weight are normal in most infants but skeletal growth falls off sharply.  By 1-2 years of age, diagnostic skeletal changes are present and consist of short and misshapen bones of the limbs and spine, and abnormal growth plates.  Adult height is typically more than 5 SDs below the mean.  In addition to short long bones other findings may include:  a prominent forehead, a short nose, curved clavicles, joint laxity, lordosis, kyphosis, oval shaped vertebrae in infancy, bowed forearms with limited elbow extension, metaphyseal flaring of long bones, short and broad phalanges with cone shaped epiphyses and short nails.  Natriuretic peptide receptor B (NPRB) is a transmembrane receptor. Its ligand is C-type natriuretic peptide.  NPRB has guanylate cyclase activity and plays a major role via downstream signaling in skeletal growth and development.