Short Stature Differential Diagnoses

Updated: Jan 06, 2021
  • 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) [9]

      • 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