This page is dedicated to the Idiopathic Short Stature research study, one of 57 studies supported by the Boston Children’s Rare Disease Collaborative (CRDC). For more information about the CRDC, please visit our home page. Established in 2018, the CRDC supports pediatric rare disease research and provides families with genetic diagnoses that enable personalized treatments, including precision medicine and targeted therapies.

The Idiopathic Short Stature research study, established at Boston Children’s in 2019 and led by Drs. Joel Hirschhorn and Jia Zhu and has already enrolled 86 patients and their families.

Disease information

Patients with idiopathic (unexplained) short stature are older than the age of 3 years old and are at or below the fifth percentile for average height for their age (prior to starting growth hormone therapy). 

It is estimated that 10 to 30% of individuals with idiopathic short stature have an underlying genetic cause for their condition. Learn more about idiopathic short stature at Boston Children’s.

Key outcomes

Ten percent of patients have received diagnostic results leading to changes in treatment plans and an additional 10% have candidate findings that are being further researched.

Genes associated with short stature

ACAN, BMP2, BMP4, GH1, GHSR, IGF1, IGF1R, IGFBP3, NPR2, PTPN11, SHOX, SOS1
(*Not an inclusive list)

Participate in research

Physicians may refer their patients with idiopathic short stature to Drs. Hirschhorn and Zhu. Once study eligibility is confirmed, a research coordinator will reach out to the family to consent and enroll them. Read more about their research on the Hirschhorn Lab webpage and Dr. Zhu's publications.

Patient care

Patients and their families with idiopathic short stature can be seen by an expert multidisciplinary team in the Division of Endocrinology at Boston Children’s.

Patient stories

In 2023, we evaluated a 6-year-old boy with severe short stature and an advanced bone age. Previously, he was followed by endocrinology since the age of 2 without a diagnosis. Upon enrolling in the CRDC study, whole exome sequencing identified a mutation in the ACAN gene, which is associated with familial short stature and early onset arthritis. This finding explains the patient’s short stature and extended family history of short stature and early onset arthritis across at least three generations. Uncovering this diagnosis enabled the family to secure growth hormone treatment to support his growth and prompted changes in the orthopedic care plan of affected family members.

Investigators

Division

Endocrinology

Notable publications by investigators

  1. Genetics of skeletal proportions in two different populations.
  2. Contributions of Common Genetic Variants to Constitutional Delay of Puberty and Idiopathic Hypogonadotropic Hypogonadism.
  3. De novo mutations in ARID1B associated with both syndromic and non-syndromic short stature.
  4. Heterozygous mutations in natriuretic peptide receptor-B (NPR2) gene as a cause of short stature.
  5. Short stature, accelerated bone maturation, and early growth cessation due to heterozygous aggrecan mutations.
  6. A positively selected FBN1 missense variant reduces height in Peruvian individuals.
  7. A novel ERCC6 splicing variant associated with a mild Cockayne syndrome phenotype.
  8. Genetic evaluation of short stature.
  9. Whole exome sequencing reveals a novel mutation in CUL7 in a patient with an undiagnosed growth disorder.
  10. Genome-wide association of copy-number variation reveals an association between short stature and the presence of low-frequency genomic deletions.
  11. Genetic and genomic approaches to studying stature and pubertal timing.
  12. A novel deletion of IGF1 in a patient with idiopathic short stature provides insight Into IGF1 haploinsufficiency.
  13. Large-scale pooled next-generation sequencing of 1077 genes to identify genetic causes of short stature.

Disease support organizations

Human Growth Foundation

The Human Growth Foundation (HGF) is the oldest nonprofit organization of its kind, serving as a global leader in endocrine research, education, patient advocacy, and support to parents of children with growth & bone conditions.

The MAGIC Foundation

The MAGIC Foundation is a charitable non-profit organization created to provide support services for the families of children afflicted with a wide variety of chronic and/or critical disorders, syndromes and diseases that affect a child's growth.

Trusted sites

NORD Report