Description

• Short stature is height 2 standard deviations (SD) or more below mean or <3rd percentile for age and sex of the normal population.
• Growth failure is defined as height 2 SD or more, below midparental height (MPH), or height velocity (HV) <10th percentile for age resulting in downward crossing of height percentiles.
• The majority of children with short stature are essentially healthy. Conversely, true growth failure is typically pathologic and requires evaluation.
• Failure to thrive (FTT) is failure of appropriate weight gain (decreasing weight to height ratio); may be accompanied by poor linear growth

Risk Factors

• Poor nutrition, systemic chronic illness, certain medications, and psychosocial factors can all contribute to the clinical presentation of short stature or growth failure.
• A family history of short stature or delayed growth and puberty are well-established risk factors for childhood short stature.

Pathophysiology

• Adequate nutrition and weight gain play major roles in linear growth during childhood.
• Throughout infancy and childhood, growth hormone (GH) and thyroid hormone exert major influences on normal growth.
• Pulsatile GH release stimulates insulin-like growth factor 1 (IGF-1) secretion from the liver and other tissues to promote growth at growth plates.
• The pubertal growth spurt is largely mediated by androgen and estrogen activity at the growth plate as well as enhanced GH release.
• Chronic illnesses can cause growth failure.
• Glucocorticoid excess inhibits growth through downregulation of the GH/IGF-1 axis and suppresses osteogenesis.
• Although boys are more frequently referred for short stature, girls are more likely to have a pathologic reason for short stature.

History

• Question: Have length/height and weight been measured correctly and charted appropriately on the correct growth curve?
• Significance: Interpretation of growth depends on precise and accurate measurements that account for both year and month of age.
• Question: Is the child short for his or her MPH?
• Significance: Height can only be judged to be inappropriate in the context of the genetic potential as determined by MPH:
  • For boys: [father’s height (cm) + (mother’s height [cm] + 13)] divided by 2
  • For girls: [(father’s height [cm] − 13) + mother’s height (cm)] divided by 2
  • MPH target range (± 2 SD) is +/− 10 cm.
  • If the child’s height percentile is decreased relative to the MPH range, evaluation may be warranted.
• Question: HV?
• Significance: A normal HV is reassuring, whereas noting a reduced HV for age/gender, regardless of absolute height, can result in earlier detection of a growth-slowing disorder.
  • The HV for an interval of at least 6 months (to minimize seasonal variation or measurement error) should be annualized.
  • As a general rule, normal HV is at least >4 cm per year in children (faster prior to age 6 years) and >8 cm per year during pubertal growth spurt.
• Question: Birth measurements and gestational age?
• Significance: Intrauterine growth restriction (IUGR) and/or small for gestational age (SGA) can be associated with possible maternal disorders, genetic disorders, and intrauterine drug exposure or stress that later impact growth.
• Question: Postnatal history including hypoglycemia or prolonged jaundice?
• Significance: Birth trauma, prolonged jaundice, and postnatal hypoglycemia can be associated with hypopituitarism.
• Question: Family history of short stature or delayed puberty?
• Significance:
  • Short stature in family members may suggest a heritable growth disorder.
  • Consider a diagnosis of constitutional delay of growth and puberty.
• Question: Dietary and feeding history?
• Significance: Low daily intake, difficulty feeding, or inefficient use of calories may point to anorexia or malabsorptive states.
• Question: Developmental milestones?
• Significance: Delays may signal chromosomal, metabolic, or behavioral syndromes.
• Question: Social situation?
• Significance: Psychosocial stressors affect growth and development.
• Question: Chronic illness or any prior hospitalizations, surgery, or head trauma?
• Significance: Growth failure may be the first/only sign of diseases such as rheumatoid arthritis, celiac disease, or inflammatory bowel disease (IBD). Previous hospitalizations, trauma, or surgery may be a sign of underlying or acquired pathology. Head trauma may cause hypopituitarism.
• Question: Any medication use?
• Significance: Use of oral or inhaled steroids as well as stimulant medications can lead to short stature or growth deceleration.
• The history should be completed by obtaining a full review of systems, specifically inquiring about general development, headache, emesis, vision change, anorexia, fatigue, weight change, bowel irregularities, pubertal development, exercise tolerance, polyuria and polydipsia, activity pattern, sleep hygiene.

Physical Exam

• Finding: Decreased upper to lower segment ratio?
• Significance: suggests scoliosis
• Finding: Abnormal trunk-to-arm span ratio?
• Significance: suggests skeletal dysplasia
• Finding: Low weight-to-height ratio?
• Significance: FTT, malnutrition, psychosocial deprivation, stimulant medication, chronic systemic illness, or metabolic disorders
• Finding: Proportionate/high weight-to-height ratio?
• Significance: if normal/near normal HV, then familial short stature, genetic syndrome, SGA, constitutional delay, mild chronic disease, prior resolved growth-attenuating disorder, or acquired growth limitations; if associated with low HV, suggests endocrine disorder, chronic disease, or growth-affecting medications
• Finding: Dysmorphic features?
• Significance: primary growth disorders
• Finding: Mid-facial hypoplasia, cherubic appearance, truncal fat deposition?
• Significance: suggests GH deficiency
• Finding: Goiter, edema, slow relaxation of deep tendon reflexes, hair loss, dry skin?
• Significance: suggests hypothyroidism
• Finding: Abdominal distention or tenderness and gluteal wasting?
• Significance: malabsorption and celiac disease
• Finding: Webbed neck, increased carrying angle, shield chest, lymphedema, heart murmur?
• Significance: Turner or Noonan Syndrome
• Finding: Microphallus?
• Significance: hypogonadism, GH deficiency
• Finding: Abnormal funduscopic or cranial nerve exam? Midline abnormalities?
• Significance: CNS pathology ± associated hypopituitarism
• Finding: Signs of neglect or abuse?
• Significance: psychosocial dwarfism
• Finding: Round face, hypocalcemia, short 4th and 5th metacarpals, and mental retardation?
• Significance: pseudohypoparathyroidism
• Finding: Hypertension, virilization, moon face, buffalo hump, thick violaceous striae?
• Significance: glucocorticoid excess
• Finding: Delayed pubertal maturation?
• Significance: Turner syndrome, constitutional delay, hypogonadism, hypothyroidism, IBD, chronic renal disease
• Finding: Leg bowing, widening of wrists, rachitic rosary, frontal bossing?
• Significance: rickets, malabsorption

Differential Diagnosis

• Extremes of normal growth:
  • Familial short stature
    • Normal exam, no systemic illness
    • Height <3rd percentile with normal HV
    • Normal bone age (BA) and onset of puberty
    • Adult height close to MPH
  • Constitutional delay of growth and puberty
    • Family history common
    • Normal exam, no systemic illness
    • Proportionately short; height percentile below MPH
    • Decelerating HV during first 3 years of life with normal to near-normal HV until puberty, when delays in pubertal growth spurt leads to decreased HV compared to peers
    • Delayed BA and pubertal maturation
    • Adult height commensurate with MPH
  • Idiopathic short stature
    • Categorizes otherwise normal patients who cannot be diagnosed with a variant of normal growth or other short stature cause
    • Predicted adult height is >2 SD below MPH.
    • Height is <3rd percentile ± delayed BA.
• Primary growth disorders: disorders intrinsic to skeletal system, BA normal
  • Skeletal dysplasia/defects: may lead to disproportionate short stature. Skeletal involvement can be subtle.
    • Skeletal radiographs with typical findings
    • Common forms: achondroplasia, hypochondroplasia, dyschondrosteosis (Leri-Weill and other SHOX mutations)
  • Syndromes
    • Usually associated with other abnormalities
    • Clinical findings may be subtle (mosaicism).
    • Common forms: trisomies (13, 18, 21), Turner or Noonan syndrome, Prader-Willi, DiGeorge, neurofibromatosis type 1
  • IUGR and SGA
    • Often due to maternal, fetal, or placental problems and/or exposures, or idiopathic
    • SGA infants have relative GH resistance seen as elevated GH with low IGF-1 levels.
    • 10% of infants with SGA don’t have catch-up growth with height SD <−2 by 2 years and need endocrine evaluation. GH therapy may be indicated.
  • Primordial dwarfism: inherited intrinsic defect leading to prenatal and postnatal growth failure
• Secondary short stature
  • Malnutrition
    • Most common cause internationally
    • Poor nutrition (caloric, vitamin, mineral)
    • Especially <2 years of age
  • Chronic illness: Poor growth can be presenting symptom.
    • Hematopoietic (anemia, sickle cell)
    • Cardiovascular (congenital heart defect)
    • Pulmonary (severe asthma, cystic fibrosis)
    • GI/liver (IBD, celiac disease, malabsorption syndromes, chronic liver disease)
    • Renal (renal tubular acidosis, Fanconi syndrome, uropathy, congenital anomalies)
    • Metabolic (poorly controlled diabetes mellitus, storage disorders, disorders of calcium and phosphorous metabolism)
    • Infectious/immunologic (HIV)
  • Iatrogenic
    • Medications: glucocorticoids, stimulants
    • Treatment of childhood malignancy, irradiation, chemotherapy
  • Psychosocial growth retardation
    • Emotional deprivation
    • Anorexia
    • Depression
  • Endocrine
    • GH or IGF-1 deficiency/resistance, hypogonadism, hypothyroidism, Cushing syndrome, short stature from earlier accelerated bone maturation (e.g., precocious puberty, hyperthyroidism, congenital adrenal hyperplasia)
    • Among secondary short stature, endocrine causes are least frequent.

Diagnostic Tests and Interpretation

• Test: Radiograph of the left hand and wrist
• Significance: BA determination (not reliable in kids <2 years of age)
• Test: IgA and anti-tissue transglutaminase IgA
• Significance: celiac disease
• Test: CBC with differential
• Significance: anemia, infection, malignancy, or chronic inflammatory conditions
• Test: C-reactive protein (CRP) and/or erythrocyte sedimentation rate (ESR)
• Significance: infection, inflammatory conditions
• Test: complete metabolic panel
• Significance: renal/liver disorders, malnutrition, calcium disorders
• Test: urinalysis
• Significance: diabetes, renal/metabolic issue
• Test: T₄/free T₄ and TSH
• Significance: hypothyroidism
• Test: karyotype or targeted gene testing
• Significance: Turner syndrome in girls, SHOX mutation, or other chromosomal disorders
• Test: IGF-1 and Insulin-like growth factor-binding protein 3 (IGF-BP3) concentrations, compared to pubertally matched norms
• Significance: proxy measurements for GH secretory reserve and screen for GH deficiency; not reliable <3 years of age and IGF-1 can be falsely low in poor nutrition states

General Measures

Evaluation warranted if HV low for age or growth pattern deviates significantly from the MPH target.

• In the majority of short children, history and exam are unrevealing, and tests yield equivocal or normal results. These children are then considered to have idiopathic short stature.
• Observation is reasonable for familial short stature or constitutional delay.
• In cases of malnutrition, restoration of adequate nutrition results in HV acceleration.
• In cases of endocrinopathies, replacement of the deficient hormone (thyroid hormone for hypothyroidism, GH for GH deficiency, hydrocortisone for adrenal insufficiency) or removal of excess hormone (glucocorticoids) will normalize the HV.
• Children with short stature or poor predicted adult height, who do not have true GH deficiency, may receive different evaluation and treatment options depending on costs, risks, physician practice, extent of family’s concern, and presence of associated psychosocial stressors (e.g., teasing by peers).

Issue for Referral

• Critical to obtain accurate measurements plotted appropriately to assess growth
• Referrals should be guided by abnormal laboratory evaluations or clinical suspicion (i.e., nephrology referral for elevated creatinine, pulmonary referral for clubbing).
• Endocrine referral warranted if slow HV, growth plateau, delayed bone age with short stature/ growth failure, or suggestive labs.
• If poor weight gain, consider nutritional deficiency, malabsorption syndromes; initial referral to gastroenterologist appropriate
• The evaluation of growth failure or short stature best done in outpatient setting

ICD-9

• 783.43 Short stature
• 259.8 Other specified endocrine disorders
• 253.3 Pituitary dwarfism

ICD-10

• R62.52 Short stature (child)
• E34.3 Short stature due to endocrine disorder
• E23.0 Hypopituitarism

SNOMED

• 237836003 Short stature disorder (disorder)
• 367460001 Pituitary dwarfism
• 216693007 Hypothyroid dwarfism (disorder)
• 237837007 Primordial dwarfism (disorder)