What is Idiopathic Short Stature?
Idiopathic short stature (ISS) is defined as height more than two standard deviations below the mean for age and sex without an identifiable pathological cause, including no identifiable disorder of the growth hormone/insulin-like growth factor axis, no endocrine abnormalities, and no genetic or organ system disorders. 1, 2
Core Diagnostic Criteria
ISS represents a diagnosis of exclusion after ruling out specific causes of short stature:
- Height threshold: The child's height must be below -2 standard deviations (or below the 3rd percentile) for age and sex 1, 3
- Normal GH/IGF-I axis: No identifiable disorder of growth hormone or insulin-like growth factor function 2
- Absence of systemic disease: No endocrine, genetic, chromosomal, or organ system disorders identified through standard diagnostic workup 2, 4
- Normal growth velocity: Growth velocity during childhood is typically normal or near-normal (4-7 cm/year), though the child remains consistently short 5
What ISS Includes (Heterogeneous Group)
This diagnosis encompasses several distinct patterns that cannot be differentiated by current testing:
- Familial short stature: Normal bone age matching chronological age, early deceleration in linear growth, predicted adult height short but appropriate for parental heights 6, 5
- Constitutional delay of growth: Delayed bone age, normal growth velocity, delayed pubertal development, with final adult height typically within normal range 5, 7
- Combined patterns: Children with both familial short stature and constitutional delay 2
- Subtle skeletal dysplasias: Mild cartilage and bone abnormalities not apparent on routine evaluation 2, 5
- Unidentified genetic variants: SHOX gene mutations occur in 1.1-12.5% of ISS cases depending on selection criteria, though most remain genetically unexplained 5, 3
Key Distinguishing Features from Pathologic Short Stature
ISS differs from pathologic causes by several characteristics:
- Proportionate body habitus: No disproportionate skeletal measurements (normal sitting height to standing height ratio) 5, 8
- Absence of dysmorphic features: No facial abnormalities, limb deformities, or syndromic features 5, 8
- No crossing of growth centiles: After age 3 years, the child maintains their growth curve without crossing multiple centile lines downward, which would suggest pathologic causes 5
- Normal screening laboratories: Thyroid function, complete blood count, and metabolic panels are normal 8
Clinical Significance and Natural History
Understanding the prognosis is essential for counseling:
- Adult height outcome: Without treatment, children with ISS will have short adult stature 9, 4
- Catch-up growth patterns: Healthy infants with intrauterine growth restriction typically complete catch-up growth by age 2 years; failure to do so warrants genetic evaluation 5, 8
- Psychosocial impact: Children and adults with short stature face documented disadvantages compared to peers, though debate continues regarding the psychological benefit of height increase through medicalization 4, 9
Common Diagnostic Pitfalls
Several scenarios require careful interpretation:
- Infants under 3 years: Healthy large infants often cross centiles in the first 3 years of life to establish a growth curve appropriate for their genetic potential—this is normal, not pathologic 5
- SHOX mutations: Skeletal changes of dyschondrosteosis may not be apparent until late childhood or pubertal age and are less commonly noted in males; skeletal survey should be considered in familial short stature cases to identify subtle changes 5
- Severe short stature: Height below -3 standard deviations warrants skeletal survey even if no other diagnosis is apparent 5