• Clinical science

Short stature

Abstract

Short stature in children is defined as a height that is at least two standard deviations below the mean for children of the same age and sex. In adults, the condition is commonly defined as a height of 5'1'' (155 cm) or less in men and 4'10″ (147 cm) or less in females. Short stature is most commonly familial or caused by a constitutional delay in growth and puberty. These cases are typically normal variants and seen in children in which one or both parents showed similar development. While height may be below average in cases of short stature, development is normal. Pathological causes of short stature include a variety of conditions, such as genetic, endocrine, and metabolic disorders, but also psychosocial circumstances. Diagnostic measures are 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 is made to determine bone age (skeletal age) and subsequently predict the adult size of the child. Laboratory tests help to further rule out a possible underlying condition. Treatment (e.g., growth hormone supplementation) is usually only indicated if a pathological cause for growth delay is detected.

Definition

  • Short stature: height of 2 or more standard deviations below the mean for children of the same age, sex, and, ideally, race and ethnicity; or an adult height of 4'10″ (147 cm) or less
  • Proportionate short stature: limbs proportionate to trunk; seen in most cases of familial short stature
  • Disproportionate short stature: limbs disproportionately short compared to trunk; seen mostly in cases of skeletal dysplasia
  • Growth failure: growth rate below normal

Height is usually increased by 50% at 1 year of age, doubles at 4 years of age, and triples at 13 years of age!

Reference values for normal growth and development

Children pass through an infantile, childhood, and pubertal growth phase, each of which has its own characteristics.

  • Infancy: Normal growth ranges between the 10th and 90th percentile and should be somewhere between 30-35 cm (11.8″–13.8″) by the 2nd year.
  • Childhood
    • 2–4 years of age: 2.2–3.5″ (5.5–9 cm) per year
    • 4–6 years of age: 2–3.3″ (5–8.5 cm) per year
    • 6 years of age to puberty:
      • 1.8–2.6″ (4.5–6.5 cm) per year
      • 1.6–2.4″ (4–6 cm) per year
  • Puberty:characterized by growth spurts of 3″–5.5″ per year, beginning around the age of 10 (may be as early as 8 years) in girls and the age of 12 (as early as 10 years) in boys
  • Midparental height (target height):
    • = [mother's height in cm + (father's height in cm - 13)]/2
    • = [father's height in cm + (mother's height in cm + 13)]/2

According to the Rule of Fives, normal growth rates in children can be approximated by multiples of five: birth–1 year (50–75 cm, 25 cm/year), 1–4 years (75–100 cm, 10 cm/year), 4–8 years (100–125 cm, 5 cm/year), 8–12 years (125–150 cm, 5 cm/year).

Bone development (ossification)

References:[1][2]

Causes of short stature

Causes of short stature Pathophysiology Specific features
Nonpathological

Familial short stature

  • Inheritance of parental short stature
  • Normal development; skeletal age consistent with chronological age
Constitutional growth delay
  • Usually history of one or both parents with delayed development
Idiopathic short stature
  • Diagnosis of exclusion in the absence of an underlying condition
  • Height of at least 2 standard deviations below the mean for age
Prenatal disorders
Endocrine Congenital hypothyroidism

Pseudohypoparathyroidism (Albright hereditary osteodystrophy)

Growth hormone (GH) deficiencies
  • Growth retardation
  • ↓ bone density and muscle atrophy
Congenital adrenal hyperplasia
  • Vomiting and dehydration during first weeks of life
  • Temporary above average stature but adult stature below average

Glucocorticoid excess

  • Excessive-weight-for-height
  • Cushingoid features
Gastrointestinal disease

Inflammatory bowel disease

Celiac disease

  • Poor-weight-for-height
Renal disease (chronic renal failure)
  • Mineral bone disorder
  • Abnormalities in the GH/IGF-1 system
  • Chronic anemia due to reduced EPO production
Pulmonary disease Asthma
  • Rate of short stature in atopic children 2–5 times higher than normal
Cystic fibrosis
Cardiac disease and chronic oxygen deficiency
  • Anorexia and increased energy requirements
Rheumatological diseases (juvenile arthritis)
  • Stiffening, deformation of joints and growth retardation
Metabolic diseases Diabetes mellitus type 1
  • Severe glucosuria → caloric deficit
  • Excessive thirst and urination
Rickets
  • Vitamin D deficiency → hypophosphatemia
  • Abnormal epiphyseal development, and bowing of the extremities
Immunologic diseases HIV
SCID
Genetic

Turner syndrome

Down syndrome

Williams syndrome

Fanconi syndrome

Noonan syndrome

Skeletal dysplasias (achondroplasia, osteogenesis imperfecta)

  • See respective links for more information
  • Varying degrees of skeletal abnormalities with short stature
Neoplasms
Psychosocial and psychological
  • Signs of neglect: poor growth or weight gain, poor hygiene, poor record of school attendance and medical care, abnormal parent–child interaction
  • Behavioral changes: e.g., apathy, anxiety, inattentiveness, aggression
  • Also see child abuse.


References:[3][4][5][6][7][8]

Diagnostics

  • Evaluation of possible causes (see “Causes of short stature” above)
    • Family history
    • Midparental height (target height)
      • = [mother's height in cm + (father's height in cm - 13)]/2
      • = [father's height in cm + (mother's height in cm + 13)]/2
    • CBC, differential blood count, ESR
    • Thyroid function tests (see hypothyroidism)
    • Renal function tests and urinalysis
    • Screening for GH deficiency (see hypopituitarism)
    • Hormone profile to assess puberty status (LH, FSH, estrogen/testosterone)
    • Genetic karyotyping
  • X-ray
    • Anterior posterior image of left hand and wrist
    • Bone age is determined and adult height is predicted by comparing x-ray images of the hand to images of bones in a standard atlas of bone development, which is based on data from large numbers of other children of the same age and gender.

References:[9]

Treatment

Management depends on the underlying cause:

  • Reassurance that short stature is normal (familial, constitutional) in most cases
  • Discontinue growth-inhibiting medication
  • Consider hormone substitution in children with delayed puberty and growth
  • GH supplementation in cases of GH deficiency, idiopathic short stature, or Turner syndrome
  • Levothyroxine supplementation in hypothyroidism

References:[9]

Skeletal dysplasias

Achondroplasia

Osteogenesis imperfecta (“brittle bone disease”)

  • Etiology: : rare, autosomal dominant mutation in COL1A1 or COL1A2 genes; ;decreased formation of hydrogen and disulfide bonds between type 1 preprocollagen molecules → decreased triple helix formation → defective type I collagen synthesis → impaired bone matrix formation (osteogenesis)
  • Clinical features
    • Growth retardation
    • Skeletal deformities, brittle bones, and recurrent fractures from minimal trauma
    • Blue sclerae
    • Progressive hearing loss
    • Brittle, opalescent teeth
    • Ligamentous laxity and joint hypermobility
    • Type II: most severe form; lethal perinatally or within the first year
  • Diagnostics
    • DNA test
    • Ultrasound before birth and radiographic skeletal survey afterwards (fractures, callus, deformities)
    • Bone or skin biopsy to examine collagen
  • Therapy
    • No cure available
    • IV bisphosphonates to increase cortical thickness
    • Surgery for functional improvement
    • Walking aids; wheelchairs; devices to improve patient's mobility and function
    • In the future: hematopoietic stem cell therapy; gene therapy

References:[10][11][12][13][14][15][16][17]