Major causes of short stature

	Distinguishing features	Typical evaluation	Treatment	Bone age	Height velocity
Normal variants of growth
Familial short stature^*	Short parent(s), often below the 10^th percentile. Adult height short for population but within the range predicted by parents' height.	Hx, PE, bone age.	None needed. Reassurance; monitor growth.	Normal	Low-normal Eg, from age 6 until puberty: Girls approximately 4 to 5 cm/year Boys approximately 3.5 to 4.5 cm/year
Constitutional delay of growth and puberty^*	Normal height for bone age but not for chronologic age. Often, family history of delayed growth and/or puberty. Adult height usually normal.	Hx, PE, bone age. Be alert for the possibility of underlying systemic disease Laboratory screening if height velocity is slow	None needed. Reassurance; monitor growth; +/– treatment with sex steroids during puberty.	Delayed	Slow during first 3 to 5 years of life; normal during childhood; pubertal growth spurt is delayed but prolonged, often resulting in normal adult height
SGA infant, with catch-up growth	Most SGA infants catch up by 2 years of age; the remainder have slower or absent catch-up growth that can be considered pathologic.	Hx, PE, bone age. For prematurely born infants, adjust height for gestational age (up to 1 year of chronologic age)	Monitor growth to distinguish from the 10% of SGA infants who do not have catch-up growth.	Normal	Normal
Pathologic causes of growth failure
Systemic disorders or processes with secondary effects on growth
Undernutrition	Low weight-for-height.	Hx (including dietary and social Hx), PE, bone age.	Reverse nutritional deficit.	Delayed or normal	Slow (eg, <4 cm/year)
Glucocorticoid therapy	Growth effects are dose related, greatest with systemic dosing. Mild effects may occur with long-term use of inhaled glucocorticoids.	Hx, PE. Assess contribution of underlying disease to growth deficit	Minimize glucocorticoid dose or give on alternate days if feasible; consider alternate drugs.	Delayed	Slow
GI disease (especially Crohn disease and celiac disease)	GI symptoms (diarrhea, abdominal pain). Crohn disease may have oral ulcers and anal fissures/skin tags.	Hx, PE, bone age. Screening laboratory tests including CBC, ESR or CRP, celiac serologies	Diagnose and treat underlying disease, improve nutrition, avoid glucocorticoids.	Delayed	Slow
Rheumatologic disease (especially systemic-onset juvenile idiopathic arthritis)	Fever, arthralgias, rash, lymphadenopathy.	Hx, PE, bone age. Screening laboratory tests including CBC and ESR or CRP, ANA, RF	Diagnose and treat underlying disease, improve nutrition, avoid glucocorticoids.	Delayed	Slow
Kidney disease (CKD, renal tubular acidosis)	Growth impairment may precede the diagnosis of CKD. Other symptoms of CKD may include polyuria, edema, elevated creatinine, tea-colored urine, and hypertension.	Hx, PE, bone age. Screening laboratory tests including BUN, creatinine, and urine analysis	Diagnose and treat underlying disease, maximize nutrition; GH if needed.	Delayed	Slow
Cancer	Any cancer – Multiple mechanisms for growth failure, including decreased intake, increased energy needs Brain cancer – Direct effects on hypothalamic-pituitary function Cancer treated with CNS radiotherapy or chemotherapy – May have direct effects on GH production, with late effects on growth	Hx, PE, bone age. For children with history of cancer, or with CNS symptoms or hypothalamic-pituitary disease – Screening laboratory tests to assess pituitary function (free T4, IGF-1, IGFBP-3), +/– head MRI with contrast	Ensure adequate nutrition; treat any secondary pituitary hormone deficiencies (eg, GH deficiency).	Delayed	Slow
Pulmonary disease (eg, cystic fibrosis, immune deficiencies with recurrent pulmonary infections, or severe asthma)	Respiratory symptoms, recurrent infections: In CF – Steatorrhea/GI symptoms, failure to thrive	Hx, PE, bone age. Test for CF and immune deficiencies.	Diagnose and treat underlying disease, ensure adequate nutrition, avoid glucocorticoids.	Delayed	Slow
Immunologic disease	Recurrent infections (manifestations vary depending on type of immunodeficiency).	Hx, PE, bone age. Work-up for immune deficiencies (refer to topic review on children with recurrent infections)	Diagnose and treat underlying disease.	Delayed	Slow
Endocrine causes of growth failure
Hypothyroidism	Sluggishness, lethargy, cold intolerance, constipation, decreased reflexes.	Hx, PE, bone age. TSH and free T4; if hypothyroidism is central (low TSH and low T4), also assess for other pituitary hormone deficiencies.	Thyroid hormone replacement.	Delayed	Slow
GH deficiency	Progressive growth failure. May also have symptoms of other pituitary hormone deficiencies.	Hx, PE, bone age. Measurements of GH, IGF-I, and IGFBP-3^¶	rhGH.	Delayed	Slow
Precocious puberty	Virilization.	Hx, PE, bone age. LH, FSH^¶	Treatment depends on type of precocious puberty.	Advanced	Initially fast, then stops early
Cushing syndrome	Obesity with central fat distribution; suprascapular fat pad; purple striae.	Hx, PE, bone age. 24-hour urine collection for free cortisol	Diagnose and treat underlying disease.	Delayed	Slow
Pseudohypoparathyroidism type 1	Brachydactyly, short stature, early-onset obesity, ectopic ossifications, sometimes with neurodevelopmental deficits. Resistance to PTH, with or without resistance to TSH and gonadotropins.	Hx, PE, bone age. Serum calcium, phosphate, PTH Molecular genetic testing (GNAS complex locus)	Refer to UpToDate content on treatment of hypocalcemia.	Advanced	Initially normal or fast, then stops early
Genetic diseases with primary effects on growth
Turner syndrome	Square "shield" chest, webbed neck, cubitus valgus^Δ, genu valgum, Madelung deformity^◊. Up to 50% have only short stature and absent pubertal development.	Karyotype analysis (for 45,X, structural abnormality of X, or mosaic).	Estrogen, GH.	Normal	Slow
SHOX mutations	May have isolated short stature (usually stocky appearance) or additional features: shorter forearms and lower legs, cubitus valgus^Δ, Madelung deformity^◊, high-arched palate.	Molecular genetic testing for SHOX abnormalities.	Consider GH.	Normal	Slow
Noonan syndrome	Minor facial dysmorphism, heart disease, intellectual disability, webbed neck, pectus excavatum, cryptorchidism.	Molecular genetic testing for PTPN11, SOS1, and other genes^¶.	Consider GH.	Normal	Low-normal or slow
Silver-Russell syndrome	Severe intrauterine growth restriction and postnatal growth retardation. Prominent forehead, triangular face, downturned corners of the mouth, and body asymmetry (hemihypertrophy).	Clinical diagnosis, supported by molecular genetic testing^¶.	Consider GH.	Normal	Slow
Skeletal dysplasias
Achondroplasia	Short arms and legs, midface hypoplasia, trident hands. Most cases identified prenatally or in early infancy.	Clinical diagnosis. Genetic testing for FGFR3 gene mutations is available^¶	Management of complications, which may include craniocervical junction compression, sleep apnea, spinal stenosis.	Mildly delayed	Slow
Hypochondroplasia	Short arms and legs similar to but milder than in achondroplasia; lumbar lordosis. May include macrocephaly, epilepsy.	Skeletal survey. Genetic testing for FGFR3 gene mutations (positive in 70%)	Surveillance for spinal stenosis, with surgery as needed.	? Normal	Slow
Spondyloepiphyseal dysplasia	Heterogeneous manifestations; trunk disproportionately shortened compared with limbs; may develop scoliosis, kyphosis, and osteoarthritis.	Anthropometrics; skeletal survey.	Surveillance for spinal disorders and osteoarthritis, with surgery as needed.	? Normal	Slow
Osteogenesis imperfecta	Children with moderate to severe disease are usually recognized by recurrent fractures but also develop short stature. Blue sclerae, scoliosis, and hearing loss may be present.	Skeletal survey.	Bisphosphonates, fracture management.	Normal	Low-normal or slow

ANA: antinuclear antibodies; BUN: blood urea nitrogen; CBC: complete blood count; CF: cystic fibrosis; CKD: chronic kidney disease; CNS: central nervous system; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; FSH: follicle-stimulating hormone; GH: growth hormone; GI: gastrointestinal; Hx: history; IGF-1: insulin-like growth factor 1; IGFBP-3: insulin-like growth factor binding protein 3; LH: luteinizing hormone; MRI: magnetic resonance imaging; PE: physical examination; PTH: parathyroid hormone; RF: rheumatoid factor; rhGH: recombinant human growth hormone; SGA: small for gestational age; T4: thyroid hormone; TSH: thyroid-stimulating hormone.

* Some patients have features of both familial short stature and constitutional delay of growth and puberty.

¶ Evaluation of patients in whom this disorder is suspected usually is performed by a subspecialist (ie, a pediatric endocrinologist, gastroenterologist, or geneticist).

Δ Cubitus valgus is an increased carrying angle of the arm.

◊ Madelung deformity is focal dysplasia of the distal radial physis, which can result in a prominent ulna and wrist pain.

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Major causes of short stature