Thricho-rhino-phalangeal syndrome and severe osteoporosis: a rare association or a feature? An effective therapeutic approach with biphosphonates

Am J Med Genet A. 2014 Mar;164A(3):760-3. doi: 10.1002/ajmg.a.36327. Epub 2013 Dec 19.

Abstract

Trichorhinophalangeal syndrome (TRPS) is a rare, autosomal dominant malformation syndrome characterized by hair, craniofacial and skeletal abnormalities, skin laxity, deformation of phalanges and anomalies of pelvis, femurs, and tibias. Three subtypes have been described: TRPS I, caused by mutations in TRPS1 gene on chromosome 8; TRPS II, a microdeletion syndrome affecting the TRPS1 and EXT1 genes; and TRPS III, a form with severe brachydactyly, due to short metacarpals, and severe short stature, but without exostoses. We present the case of a 7-year-old boy, affected by TRPS with a severe osteoporosis and several spontaneous bone fractures, an association described only once in the literature, successfully treated with biphosphonates. Bone mineral density (BMD) at dual-energy X-ray Absorptiometry (DXA) was of 0.331 g/cm(2) at lumbar spine with. He had four spontaneous femoral fractures in a year, and for this reason he was been operated for positioning intramedullary osteosynthesis and orthopedic supports. Due to the severity of the clinical and radiological pattern it was established, after approval of the Ethical Committee, to begin off-label therapy with infusions of neridronate at a dose of 2 mg/kg IV every 3 months. The treatment was, in this patient, effective both in terms of clinical (absence of new fractures) and mineralomethric (+45% BMD ath the lumbar level). We therefore suggest that treatment with biphosponates can be taken in account as a possible therapeutic option in case of bone fragility in patients with TRPSI.

Keywords: biphosphonates; neridronate; osteoporosis; trichorhinophalangeal syndrome.

Publication types

  • Case Reports

MeSH terms

  • Bone Density
  • Bone Density Conservation Agents / therapeutic use
  • Bone and Bones / diagnostic imaging
  • Child
  • Clodronic Acid / therapeutic use
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics
  • Fingers / abnormalities*
  • Hair Diseases / complications
  • Hair Diseases / diagnosis*
  • Hair Diseases / genetics
  • Humans
  • Langer-Giedion Syndrome / complications
  • Langer-Giedion Syndrome / diagnosis*
  • Langer-Giedion Syndrome / genetics
  • Male
  • Nose / abnormalities*
  • Osteoporosis / diagnosis*
  • Osteoporosis / drug therapy
  • Osteoporosis / etiology
  • Phenotype
  • Radiography
  • Repressor Proteins
  • Transcription Factors / genetics

Substances

  • Bone Density Conservation Agents
  • DNA-Binding Proteins
  • Repressor Proteins
  • TRPS1 protein, human
  • Transcription Factors
  • Clodronic Acid

Supplementary concepts

  • Trichorhinophalangeal Syndrome, Type I