The splice c.1815G>A variant in KIAA0586 results in a phenotype bridging short-rib-polydactyly and oral-facial-digital syndrome: A case report and literature review

Medicine (Baltimore). 2020 Feb;99(8):e19169. doi: 10.1097/MD.0000000000019169.

Abstract

Introduction: KIAA0586 variants have been associated to short-rib thoracic dysplasia, an autosomal recessive skeletal ciliopathy characterized by a narrow thorax, short limbs, and radiological skeletal abnormalities.

Patient concerns: Patients 1 and 2 were two Roma Gypsy siblings presenting thoracic dysplasia and a combination of oral cavity anomalies.

Diagnosis: A custom NGS gene panel, including genes associated to skeletal ciliopathies, identified the homozygous KIAA0586 splicing variant c.1815G>A (p.Gln605Gln) in both siblings, confirming the clinical diagnosis of short-rib-polydactyly.

Intervention: Patients were transferred to neonatal intensive care unit and received life-support treatment.

Outcomes: Patients 1 and 2 died after few hours and 1 month of birth, respectively, because of respiratory failure related with the disease.

Conclusion: We report two patients affected by short-rib polydactyly syndrome and overlapping phenotype with oral-facial-digital syndrome associated with the c.1815G>A variant in KIAA0586, suggesting a quite peculiar genotype-phenotype correlation.

Publication types

  • Case Reports

MeSH terms

  • Cell Cycle Proteins / genetics*
  • Ciliopathies
  • Humans
  • Infant, Newborn
  • Italy
  • Male
  • Orofaciodigital Syndromes / complications*
  • Orofaciodigital Syndromes / genetics*
  • Phenotype
  • Roma
  • Short Rib-Polydactyly Syndrome / complications*
  • Short Rib-Polydactyly Syndrome / genetics*
  • Siblings

Substances

  • Cell Cycle Proteins
  • KIAA0586 protein, human