SHORT syndrome in two Chinese girls: A case report and review of the literature

Mol Genet Genomic Med. 2020 Sep;8(9):e1385. doi: 10.1002/mgg3.1385. Epub 2020 Jun 29.


Background: SHORT syndrome is a rare inherited multisystem disease that includes characteristic facial features, growth retardation, and metabolic anomalies and is related to heterozygous mutations in the PIK3R1 gene. However, it is difficult to ascertain the relationship between the phenotype and the genotype quickly and efficiently.

Methods: We report two Chinese girls with SHORT syndrome who presented with growth retardation, dysmorphic features, insulin resistance, and diabetes. Comprehensive medical evaluations were collected, including anthropometric measurements, laboratory measurements, and imaging examinations. Whole exome and Sanger sequencing was performed to detect and confirm the underlying genetic mutations in these patients. We prescribed metformin for the patients.

Results: The patients both presented diabetes, insulin resistance, short stature, lipodystrophy, and characteristic facial dysmorphic features. A heterozygous mutation was detected in the PIK3R1 gene (c.1615_1617del) of Patient 1. The analysis of patient 2 revealed another PIK3R1 mutation (c.1945C>T). After family validation, neither their parents nor their brothers had similar clinical presentations or carried the same mutation.

Conclusion: We identified two de novo heterozygous mutations in PIK3R1 as the cause of SHORT syndrome in two Chinese girls. Additionally, in terms of diabetes control, metformin works well in the early treatment stage.

Keywords: PIK3R1; SHORT syndrome; diabetes; insulin resistance; short stature; whole exome sequencing.

Publication types

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

MeSH terms

  • Adolescent
  • Class Ia Phosphatidylinositol 3-Kinase / genetics*
  • Female
  • Growth Disorders / drug therapy
  • Growth Disorders / genetics*
  • Growth Disorders / pathology
  • Heterozygote
  • Humans
  • Hypercalcemia / drug therapy
  • Hypercalcemia / genetics*
  • Hypercalcemia / pathology
  • Metabolic Diseases / drug therapy
  • Metabolic Diseases / genetics*
  • Metabolic Diseases / pathology
  • Metformin / therapeutic use
  • Mutation
  • Nephrocalcinosis / drug therapy
  • Nephrocalcinosis / genetics*
  • Nephrocalcinosis / pathology
  • Phenotype


  • Metformin
  • PIK3R1 protein, human
  • Class Ia Phosphatidylinositol 3-Kinase

Supplementary concepts

  • SHORT syndrome