What is the diagnostic workup and treatment for a child with short stature?

Diagnostic Workup and Differential for Short Stature in Children

The diagnostic workup for short stature in children should begin with assessment of growth patterns, bone age evaluation, and targeted laboratory testing, followed by genetic testing when indicated, to identify pathologic causes that require intervention.

Definition and Initial Assessment

Short stature is defined as height-for-age less than 2 standard deviations below the mean (below 3rd percentile) 1. The evaluation should focus on:

• Growth velocity assessment: Growth velocity below the 25th percentile with height below the 3rd percentile suggests pathologic growth failure 1
• Growth pattern analysis: Crossing of several centile lines between 3 years and adolescence suggests pathology 2
• Proportionality assessment: Disproportionate short stature suggests skeletal dysplasia, while proportionate short stature may indicate endocrine or genetic conditions 1

Differential Diagnosis

Nearly 50% of children referred for short stature evaluation have non-pathologic causes 2:

1. Non-pathologic causes:

   • Constitutional delay of growth and puberty
   • Familial short stature

2. Pathologic causes:

   • Chromosomal abnormalities (19%): Primarily Turner syndrome and variants 2
   • Endocrine disorders: Growth hormone deficiency, hypothyroidism
   • Genetic conditions: SHOX gene defects, skeletal dysplasias
   • Systemic diseases: Chronic kidney disease, inflammatory bowel disease, celiac disease
   • Multiple malformation syndromes (3%) 2

Diagnostic Algorithm

Step 1: Comprehensive Clinical Evaluation

• Plot serial height measurements on appropriate growth charts
• Calculate estimated adult height and compare with midparental height
• Evaluate for dysmorphic features or skeletal disproportion
• Assess growth velocity and pattern

Step 2: Initial Laboratory Screening

• Complete blood count
• Comprehensive metabolic panel
• Thyroid function tests (TSH, free T4)
• Inflammatory markers (ESR, CRP)
• Celiac disease screening
• IGF-1 and IGFBP-3 levels

Step 3: Bone Age Assessment

• Wrist and hand radiograph for bone age determination 1
• Compare bone age with chronological age:
  • Delayed bone age: Constitutional delay, growth hormone deficiency
  • Advanced bone age: Precocious puberty, endocrinopathies with excess sex hormone production 1

Step 4: Genetic Testing (When Indicated)

• Chromosomal analysis: For girls with short stature to rule out Turner syndrome 1
• SHOX gene testing: For children with:
  • Subtle skeletal changes
  • Significant short stature (>3 SD) without other diagnosis
  • Family history of short stature or skeletal abnormalities 1
• Targeted gene panels or whole exome sequencing: When other evaluations are negative but genetic etiology is suspected 3

Treatment Approaches

Treatment depends on the underlying cause:

• Growth hormone therapy: Consider for:

  • Documented GH deficiency
  • Specific genetic syndromes including SHOX gene-related disorders 1
  • Chronic kidney disease stages 3-5 when height is below 3rd percentile 1

• GnRH agonists: For precocious puberty to slow bone maturation 1

• Contraindications for GH therapy:

  • Accelerated bone maturation
  • Active malignancy
  • Uncontrolled diabetes mellitus
  • Pre-existing papilledema 1

Monitoring

• Regular bone age assessment every 6-12 months 1
• More frequent (every 6 months) bone age monitoring for children on GH therapy 1
• Annual IGF-1 monitoring for safety and dosage adjustment 1

Common Pitfalls to Avoid

1. Delayed diagnosis: Early identification of pathologic causes is crucial for timely intervention and preventing excessive short stature in adulthood 4

2. Overlooking subtle skeletal abnormalities: Careful physical examination for subtle dysmorphology or skeletal disproportion may indicate heterozygous mutations 3

3. Premature labeling as idiopathic short stature: Idiopathic short stature is not a diagnosis but describes a heterogeneous group of children; thorough evaluation is needed before applying this label 3

4. Failure to consider genetic testing: As genetic testing becomes more available, the pool of patients labeled as idiopathic will shrink 3

5. Missing non-endocrine causes: Nutritional deficiencies, systemic diseases, and genetic abnormalities can all cause short stature and require different management approaches 5