Diagnostic Considerations
Causes of growth failure in children include the following:
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GI
Protein or caloric deprivation
Inflammatory bowel disease -Crohn disease, ulcerative colitis
Sprue (gluten intolerance)
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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
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Panhypopituitarism (combined anterior pituitary hormone deficiencies)
PROP1 gene mutation
P OU1F1 gene mutations
Septo-optic dysplasia
LHX3
LHX4
OTX2
FGFR1
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Growth hormone-releasing hormone (GHRH) deficiency
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Poorly controlled type 1 diabetes mellitus - Mauriac syndrome
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Chronic hypernatremia - Hypothalamic adipsia, poorly controlled diabetes insipidus
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Hypercortisolism - Iatrogenic glucocorticoid administration, or Cushing syndrome
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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:
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Genetic (known defect)
Down syndrome (trisomy 21)
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
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Genetic (unknown defect)
Silver-Russell syndrome
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Pulmonic
CF
Severe asthma
Chronic obstructive pulmonary disease
Restrictive lung disease
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Cardiac
Hypoxemia
Low cardiac output states
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Renal
Chronic renal insufficiency
Renal failure
Renal tubular acidosis
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Psychosocial dwarfism
Chronic neglect
Starvation
Differential Diagnoses
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3-M Syndrome
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Genetics of von Gierke Disease (Glycogen-Storage Disease Type 1)
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Hypercalciuria
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Mauriac syndrome
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Microcephalic osteodysplastic primordial dwarfism (MOPD) type 1 and 2
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Proper use of a wall-mounted stadiometer.
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Comparison of the growth patterns between idiopathic short stature and constitutional growth delay.
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Bone age comparison between an 8-year-old boy (left) and a 14-year-old adolescent boy (right).
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Growth chart for Turner syndrome. Note that the upper limit overlaps the range for girls of normal height.
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A single, central, maxillary incisor reflects a defect in midline facial development.
