Short Stature Differential Diagnoses

Updated: Feb 09, 2018
  • Author: Sunil Kumar Sinha, MD; Chief Editor: Robert P Hoffman, MD  more...
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Diagnostic Considerations

Causes of growth failure in children include the following:

  • GI
  • Endocrine
    • Hypothyroidism
    • Primary - Hashimoto thyroiditis, Pendred syndrome
      • Secondary - Thyrotropin (thyroid-stimulating hormone [TSH]) deficiency
      • Tertiary - Thyrotropin-releasing hormone (TRH) deficiency
      • Other - Iatrogenic or environmental radioablation, neoplasm
    • Isolated growth hormone deficiency (GHD) complete absence or insufficiency (partial absence) [8]
      • Autosomal recessive GH1 gene alteration (deletions, frame shift, nonsense, missense, splice shift)
      • Autosomal dominant GH1 gene alteration (nonsense, missense, splice shift, splice enhancer)
      • Growth hormone-releasing hormone (GHRH)
      • X-linked BTX, SOX3
    • Other causes of primary IGF deficiency and IGF- 1 resistance (all isolated GHD usually cause primary IGF deficiency)
      • STAT5b gene mutation
      • IGF1 gene mutation
      • Bioinactive IGF-1 (relative IGF-1 deficiency)
      • IGF1R gene mutation
      • Acid-labile subunit (ALS) deficiency
  • Panhypopituitarism (combined anterior pituitary hormone deficiencies)
    • PROP1 gene mutation
    • P OU1F1 gene mutations
    • Septo-optic dysplasia
    • LHX3
    • LHX4
    • OTX2
    • FGFR1
  • Growth hormone-releasing hormone (GHRH) deficiency
  • Poorly controlled type 1 diabetes mellitus - Mauriac syndrome
  • Chronic hypernatremia - Hypothalamic adipsia, poorly controlled diabetes insipidus
  • Hypercortisolism - Iatrogenic glucocorticoid administration, or Cushing syndrome
  • Hypocortisolism - DAX1 gene mutation, autoimmune adrenalitis (Addison disease); (Note that adrenocorticotropic hormone deficiency alone has been associated with tall stature; short stature results from hypocortisolism only in persons with salt wasting.)

Causes of normal variant short stature (also called familial short stature) include the following:

  • Genetic (known defect)
    • Down syndrome (trisomy 21)
    • Silver-Russell syndrome
    • Hypochondroplasia
    • SHOX gene mutations
    • Turner syndrome
    • Leri-Weill dyschondrosteosis
    • Growth Hormone secretagogue receptor gene mutation (GHSR)
    • Insulin receptor gene mutations (leprechaunism)
    • Natriuretic peptide receptor- B (NPR2) mutations
  • Genetic (unknown defect)
  • Pulmonic
    • CF
    • Severe asthma
    • Chronic obstructive pulmonary disease
    • Restrictive lung disease
  • Cardiac
  • Renal
    • Chronic renal insufficiency
    • Renal failure
    • Renal tubular acidosis
  • Psychosocial dwarfism
    • Chronic neglect
    • Starvation

Differential Diagnoses