PAPSS2-related brachyolmia: Clinical and radiological phenotype in 18 new cases

Am J Med Genet A. 2019 Sep;179(9):1884-1894. doi: 10.1002/ajmg.a.61282. Epub 2019 Jul 16.

Abstract

Brachyolmia is a skeletal dysplasia characterized by short spine-short stature, platyspondyly, and minor long bone abnormalities. We describe 18 patients, from different ethnic backgrounds and ages ranging from infancy to 19 years, with the autosomal recessive form, associated with PAPSS2. The main clinical features include disproportionate short stature with short spine associated with variable symptoms of pain, stiffness, and spinal deformity. Eight patients presented prenatally with short femora, whereas later in childhood their short-spine phenotype emerged. We observed the same pattern of changing skeletal proportion in other patients. The radiological findings included platyspondyly, irregular end plates of the elongated vertebral bodies, narrow disc spaces and short over-faced pedicles. In the limbs, there was mild shortening of femoral necks and tibiae in some patients, whereas others had minor epiphyseal or metaphyseal changes. In all patients, exome and Sanger sequencing identified homozygous or compound heterozygous PAPSS2 variants, including c.809G>A, common to white European patients. Bi-parental inheritance was established where possible. Low serum DHEAS, but not overt androgen excess was identified. Our study indicates that autosomal recessive brachyolmia occurs across continents and may be under-recognized in infancy. This condition should be considered in the differential diagnosis of short femora presenting in the second trimester.

Keywords: PAPSS2; brachyolmia; platyspondyly.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Dwarfism / diagnostic imaging
  • Dwarfism / genetics*
  • Dwarfism / physiopathology
  • Exome Sequencing
  • Female
  • Genes, Recessive / genetics
  • Genetic Predisposition to Disease
  • Homozygote
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Multienzyme Complexes / genetics*
  • Musculoskeletal Abnormalities / diagnostic imaging
  • Musculoskeletal Abnormalities / genetics*
  • Musculoskeletal Abnormalities / physiopathology
  • Osteochondrodysplasias / diagnostic imaging
  • Osteochondrodysplasias / genetics*
  • Osteochondrodysplasias / physiopathology
  • Pedigree
  • Radiography
  • Spine / diagnostic imaging
  • Spine / physiopathology
  • Sulfate Adenylyltransferase / genetics*
  • Young Adult

Substances

  • Multienzyme Complexes
  • PAPS synthetase
  • Sulfate Adenylyltransferase

Supplementary concepts

  • Brachyolmia