OFFICIAL ABP TOPIC:

Understand the differential diagnosis and evaluation of a patient with short stature

BACKGROUND

Short stature is defined as a height less than 2 standard deviations (SD) below the mean for age and sex, corresponding to a height below the 2.3 percentile. Most children with short stature have familial short stature or constitutional delay of growth and puberty, but pediatricians should be able to recognize pathologic etiologies to guide appropriate evaluation and management.

DIFFERENTIAL DIAGNOSIS OF SHORT STATURE

NORMAL VARIANTS

• Constitutional delay of growth and puberty (CDGP):
  • Normal size at birth, slowed growth by 3-5 years old.
  • Delayed bone age, predicted adult height appropriate for family.
  • May have family history of “late bloomers.”
• Familial short stature (FSS):
  • Height <2.3 percentile but matches family background.
  • Normal growth velocity and bone age.
• Idiopathic short stature (ISS): A height below 2 standard deviations without a metabolic, endocrine, or other diagnosis (diagnosis of exclusion).

PATHOLOGIC ETIOLOGIES

SYSTEMIC DISORDERS:

Systemic disorders with secondary effects on growth include malnutrition, celiac disease, inflammatory bowel disease (IBD), juvenile idiopathic arthritis, kidney disease, malignancy, and cystic fibrosis:

• Growth pattern: Stunted growth with low weight-for-height.
• Diagnostic tests: CBC (anemia), ESR/CRP (inflammation), celiac panel (positive anti-tTG IgA and/or total IgA).

ENDOCRINE CAUSES

• Hypothyroidism:
  • Signs: Lethargy, cold intolerance, constipation, decreased reflexes.
  • Growth pattern: Proportionate short stature with delayed puberty.
  • Diagnostic tests: Elevated TSH, low T4.
• Growth hormone deficiency:
  • Signs: Growth failure, possibly with other pituitary hormone deficiencies.
  • Growth pattern: Proportionate short stature with delayed puberty.
  • Diagnostic tests: Low IGF-1 and IGFBP-3. If GH deficiency confirmed, obtain MRI brain with and without contrast.
• Precocious puberty:
  • Signs: Virilization, initial accelerated height velocity stops early.
  • Growth pattern: Rapid early growth with early puberty signs.
  • Diagnostic tests: Advanced bone age (>2 SD above chronological age).
• Cushing syndrome:
  • Signs: Obesity, suprascapular fat pad, purple striae.
  • Growth pattern: Proportionate short stature with delayed puberty.
  • Diagnostic tests: High 24-hour urinary cortisol.
• Pseudohypoparathyroidism Type 1:
  • Signs: Brachydactyly, obesity, ectopic ossifications, resistance to PTH. Initial normal height velocity stops early.

GENETIC SYNDROMES

• Turner syndrome:
  • Signs: Webbed neck, shield chest, coarctation of aorta.
  • Growth pattern: Proportionate short stature.
  • Diagnostic tests: Karyotype (45,X).
• Down syndrome:
  • Signs: Upslanting palpebral fissures, hypotonia, heart defects.
  • Growth pattern: Proportionate short stature.
  • Diagnostic tests: Karyotype (trisomy 21).
• Prader-Willi syndrome:
  • Signs: Hypotonia, developmental delay, hypogonadism, obesity.
  • Growth pattern: Proportionate short stature.
  • Diagnostic tests: DNA methylation analysis.
• Russell-Silver syndrome:
  • Signs: SGA, body asymmetry, frontal bossing, feeding difficulties.
  • Growth pattern: Proportionate short stature.
  • Diagnostic tests: Chromosome 7 and 11 studies.
• SHOX deficiency:
  • Signs: Madelung deformity (abnormal wrist bone alignment), short forearms and lower legs.
  • Growth pattern: Proportionate short stature.
  • Diagnostic tests: SHOX gene testing.

Skeletal dysplasias:

• Growth pattern: Disproportionate short stature.
• Diagnostic tests: Skeletal survey (abnormal bone proportions, dysplasia patterns).
• Examples: Achondroplasia, hypochondroplasia, spondyloepiphyseal dysplasia.

EVALUATION PROCESS

Growth measurements:

• <2 years old: Measure supine length.
• >3 years old: Measure standing height.
• 2-3 years old: Measure both supine length and standing height.
• Plot measurements on appropriate growth chart (WHO charts for <2 years old, CDC charts for 2-20 years old).
• Calculate height velocity over time.
• Calculate midparental height (predicted adult height of child based on genetics):
  • Girls: (Father’s height – 13 cm + Mother’s height) ÷ 2.
  • Boys: (Father’s height + 13 cm + Mother’s height) ÷ 2.

Project child’s adult height by extrapolating current height percentile to adult percentile (use bone age if bone age differs from chronological age):

• Projected height within 8.5 cm of midparental height = expected range for family.
• Projected height <8.5 cm of midparental height = abnormally short for family.

History:

• Birth history: SGA, complications.
• Medical history: Head trauma, CNS infection, chronic diseases, medications.
• Review of systems: Fatigue, abdominal pain, diarrhea, recurrent infections.
• Family history: Parental heights, pubertal timing, genetic conditions.

Physical exam:

• Dysmorphic features:
  • Webbed neck: Suggestive of Turner syndrome or other genetic syndromes.
  • Hypertelorism (wide-spaced eyes): May indicate syndromic conditions like Russell-Silver syndrome or chromosomal abnormalities (e.g., Down syndrome).
• Body proportions:
  • Limb length vs trunk ratio: Essential for identifying skeletal dysplasias, such as achondroplasia or spondyloepiphyseal dysplasia, which present with disproportionate short stature.
• Evidence of chronic disease:
  • Look for signs of systemic involvement, such as pallor (anemia), joint swelling (juvenile idiopathic arthritis), or poor weight gain (malnutrition, IBD), pointing toward chronic illnesses affecting growth.
• Pubertal staging:
  • Delayed puberty: Indicative of constitutional delay of growth and puberty (CDGP) or endocrine disorders such as growth hormone deficiency or hypothyroidism.
  • Precocious puberty: Suggests endocrine pathology like gonadotropin-independent precocity or central precocious puberty, often related to underlying structural or genetic issues.

GROWTH PATTERNS LINKED TO SPECIFIC DIAGNOSES 

DIAGNOSTIC TESTS

REFERENCES

https://www.uptodate.com/contents/causes-of-short-stature

https://www.uptodate.com/contents/diagnostic-approach-to-children-and-adolescents-with-short-stature

https://publications.aap.org/pediatricsinreview/article/38/7/293/35047/Disorders-of-Growth-and-Stature