• Clinical science

Short stature (Dwarfism)

Summary

Short stature (dwarfism) in children is defined as a height that is at least two standard deviations (SDs) below the mean for children of the same age and sex. In adults, the condition is commonly defined as a height of 5 ft 1 in (155 cm) or less in men and 4 ft 10 in (147 cm) or less in women. Nonpathological variant short stature can be classified into three types: familial short stature (inherited short stature), constitutional delay of growth and puberty (an inherited pattern of short stature during childhood that is followed by a growth spurt during puberty, typically resulting in normal adult height), and idiopathic short stature (short stature in the absence of any metabolic, endocrine, or other diagnosis). These types of short stature are most often normal variants of growth and rarely affect a child's development beyond longitudinal growth. The pathological causes of short stature are diverse and include psychosocial circumstances as well as a variety of genetic, endocrine, and metabolic disorders, which may affect a child's development in other ways than longitudinal growth. Further diagnostic testing is indicated if a child's growth is less than what might be expected given the average height of the parents. An x-ray of the left hand and wrist are made to determine bone age (skeletal age), based on which the adult size of the child can be predicted. Laboratory testing can help rule out any underlying condition. Treatment is rarely indicated in nonpathological short stature (e.g., if short stature represents a disability to the patient), while pathological short stature is treated according to the underlying condition and usually involves growth hormone supplementation.

Definition

  • Short stature (dwarfism)
    • Children: height of > 2 SDs below the mean for children of the same age, sex, and similar genetic background
    • Adults: height of ≤ 4 ft 10 in (147 cm) for women and ≤ 5 ft 1 in (155 cm) for men [1]
  • Proportionate short stature
  • Disproportionate short stature
    • Limbs disproportionately short compared to trunk
    • Seen mostly in cases of skeletal dysplasia
  • Growth failure: growth rate below the rate considered appropriate for sex and age.
  • See child development and milestones for reference ranges and growth charts.

References:[2][3]

Causes of short stature

Inherited causes

Condition Underlying causes of short stature Other features
Nonpathological variant short stature

Familial short stature

  • Hereditary short stature
  • Most common cause of proportionate short stature
  • Normal development
  • Skeletal age consistent with chronological age
Constitutional growth delay
  • Inherited type of developmental delay
  • Second most common cause of short stature
Idiopathic short stature
  • Diagnosis of exclusion in the absence of an underlying condition
  • Height of ≤ 2 SDs below the mean for age that cannot be explained by inheritance or pathological processes.
Pathological short stature
Laron syndrome
Skeletal dysplasias
  • Impaired osteogenesis
Turner syndrome
Down syndrome
  • Possibly due to selective IGF-1 deficiency
  • Craniofacial dysmorphia
  • Skeletal abnormalities
  • Developmental delay
  • Obesity
Williams syndrome
  • Cognitive impairment
  • Elfin-like facies
  • Cardiovascular abnormalities
Cystic fibrosis
  • Defective chloride channels → secretion of hyperviscous mucous → blockage of exocrine glands → chronic mucosal inflammation
Pseudohypoparathyroidism (Albright hereditary osteodystrophy)
  • Impaired bone growth due to PTH resistance
  • Obesity
  • Round face
  • Short neck
  • Brachydactyly
McCune-Albright syndrome
  • Accelerated bone maturation associated with early onset of puberty

Systemic disorders

Condition Underlying causes of short stature Other features
Endocrine disorders
Congenital hypothyroidism
GH deficiencies
  • Impaired bone and muscle development
  • Growth delay
  • Low bone density
  • Muscle atrophy
Congenital adrenal hyperplasia
  • Rapid bone maturation due to increased androgen levels
Glucocorticoid excess
Type 1 diabetes mellitus
Rheumatological diseases
Juvenile idiopathic arthritis
Renal disorders
Chronic kidney disease (CKD)
Fanconi syndrome
  • Increased phosphaturia due to impaired tubular reabsorption of phosphate
Metabolic disorders
Rickets
Gastrointestinal disorders

Celiac disease/
Inflammatory bowel disease

Chronic oxygen deficiency
Congenital heart defects
  • High energy requirements due to inappropriate gas exchange
  • Decreased nutritional intake
Anemias
  • Tissue hypoxia and low metabolism rates
Immunological diseases
HIV infection
  • Chronic immunodeficiency associated with:
    • Low dietary intake and altered metabolism
    • Low IGF-1 levels and tissue insensitivity to IGF-1
    • Increased susceptibility to diarrhea
Severe combined immunodeficiency
  • Primary deficiency in B and T cells leading to
Other causes of short stature
Neoplasms

Behavioral and psychosocial circumstances

Condition Underlying cause Specific features
Maternal substance use
Psychosocial short stature
  • Emotional deprivation or stress that typically involves neglect, abuse, or a poor relationship between the patient and caregiver and leads to:
  • Poor growth or weight gain
  • Poor record of school attendance and medical care
  • Signs of child maltreatment
  • Clinical and radiographic signs of abuse
Anorexia nervosa

Diagnostics

References:[4]

Treatment

Management depends on the underlying cause:

References:[4]

Skeletal dysplasias

Achondroplasia

Osteogenesis imperfecta (brittle bone disease)

  • Etiology: autosomal dominant mutation in COL1A1 or COL1A2 genes
  • Pathophysiology: :↓ formation of hydrogen and disulfide bonds between type I preprocollagen molecules → ↓ triple helix formation → ↓ type I collagen synthesis impaired bone matrix formation (osteogenesis)
  • Clinical features
    • Osteogenesis imperfecta type I (the mildest and the most common form)
      • Growth delay
      • Skeletal deformities, brittle bones
      • Bowing of bones and saber shins
      • Fractures during childbirth; and recurrently from minimal trauma thereafter
      • Blue sclerae (choroidal veins show through the thin sclera)
      • Progressive hearing loss
      • Brittle, opalescent teeth (dentinogenesis imperfecta; due to a lack of dentin)
      • Ligamentous laxity and joint hypermobility
    • Osteogenesis imperfecta type II
      • Most severe form; lethal perinatally or within the first year
      • Multiple intrauterine and/or perinatal fractures
      • Underdeveloped lungs and subsequent respiratory problems
  • Diagnostics
  • Therapy
    • No definitive treatment available
    • Supportive measures: walking aids, wheelchairs, devices to improve patient's mobility and function
    • Bisphosphonates; : increase cortical thickness and decrease the risk of fractures
    • Surgery: to improve mobility and correct the associated skeletal defects

In osteogenesis imperfecta, patients cannot BITE: Bones (recurrent fractures), I for “eye” (blue sclerae), Teeth (dental abnormalities), Ears (hearing loss).

Bone fractures from osteogenesis imperfecta are easily mistaken for signs of child maltreatment!

Campomelic dysplasia

  • Definition: a life-threatening disorder characterized by skeletal dysplasia, abnormal sex development, and other congenital defects due to SOX9 gene mutations [7][8]
  • Etiology
  • Clinical features
    • Skeletal abnormalities
    • Abnormalities of the reproductive system
      • Ambiguous external or normal female genitalia (despite normal 46, XY karyotype)
      • Male (testes), female (ovaries), and ambiguous internal genitalia
    • Other defects
      • Life-threatening laryngotracheomalacia
      • Respiratory distress syndrome
      • Hearing loss
  • Diagnosis
    • Clinical and radiographic findings
    • Genetic testing
  • Treatment
    • Airway protection
    • Surgical repair of congenital anomalies

References:[9][10][11][12][13][14][15][16]