Long term follow up of two independent patients with Schinzel-Giedion carrying SETBP1 mutations

Eur J Med Genet. 2015 Sep;58(9):479-87. doi: 10.1016/j.ejmg.2015.07.004. Epub 2015 Jul 15.

Abstract

Schinzel-Giedion syndrome (SGS, MIM #269150) is a rare syndrome characterized by severe intellectual disability, typical facial gestalt, hypertrichosis and multiple congenital malformations including skeletal, genitourinary, renal and cardiac abnormalities. The prognosis of SGS is very severe and death occurs generally within a few years after birth. In 2002, we reported 2 children with SGS with a follow-up of 3 years. They presented a very similar and particular phenotype associating distinctive facial gestalt, severe developmental delay, megacalycosis, progressive neurodegeneration, alacrimi, corneal hypoesthesia and deafness. Furthermore, temporal bone imaging revealed a tuning-fork malformation of the stapes. In 2010, Hoischen et al. identified in SGS patients pathogenic heterozygous de novo mutations in SETBP1. We sequenced SETBP1 in our patients and found the previously reported c.2608G>A (p.Gly870Ser) mutation in both children. Since 2002, one of our patients died at 6 years old and the other patient is still alive at 15 years old. Such a life expectancy has never been reported so far. We describe herein the follow up of the 2 children during 6 and 15 years respectively. This article gives further evidence of the implication of SETBP1 as the major gene of SGS, and reports the previously unseen natural evolution of the disease in a 15 years old patient.

Keywords: Coraliform nephrolithiasis; Dental abnormalities; SETBP1; Schinzel–Giedion syndrome.

Publication types

  • Case Reports

MeSH terms

  • Abnormalities, Multiple / diagnosis
  • Abnormalities, Multiple / genetics*
  • Adolescent
  • Amino Acid Sequence
  • Brain / abnormalities
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Child
  • Craniofacial Abnormalities / diagnosis
  • Craniofacial Abnormalities / genetics*
  • Face / abnormalities
  • Female
  • Follow-Up Studies
  • Hand Deformities, Congenital / diagnosis
  • Hand Deformities, Congenital / genetics*
  • Humans
  • Intellectual Disability / diagnosis
  • Intellectual Disability / genetics*
  • Magnetic Resonance Imaging
  • Male
  • Microcephaly / diagnosis
  • Microcephaly / genetics
  • Molecular Sequence Data
  • Nails, Malformed / diagnosis
  • Nails, Malformed / genetics*
  • Nephrolithiasis / diagnosis
  • Nephrolithiasis / genetics
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Pedigree
  • Prognosis
  • Psychomotor Disorders / diagnosis
  • Psychomotor Disorders / genetics

Substances

  • Carrier Proteins
  • Nuclear Proteins
  • SETBP1 protein, human

Supplementary concepts

  • Schinzel-Giedion syndrome