Short stature

What is short stature?¹

Short stature is defined as height that is two standard deviations below the mean height for age and sex (less than the third percentile) or more than two standard deviations below the mid-parental height. A downward growth trend suggests a slowdown in growth and possibly a growth problem.

A growth velocity disorder is defined as an abnormally slow growth rate, which may manifest as height deceleration across two major percentile lines on the growth chart.

There are many potential causes. In some cases, short stature or slow growth is the initial sign of a serious underlying disease in an otherwise apparently healthy child. However, most children with short stature will have constitutional delay of growth and puberty (CDGP) or familial short stature, or there will be no identifiable cause.

See also Faltering Growth in Children and Centile Charts and Assessing Growth.

Causes of short stature (aetiology)^{2 3}

The International Classification of Pediatric Endocrine Diagnoses (ICPED) classifies the main causes of short stature into three groups:¹

• Primary growth disorders, where the condition is intrinsic to the growth plate.

• Secondary growth disorders, where the growth plates change as a consequence of the condition.

• Idiopathic, where there is no identifiable cause of short stature.

Primary growth disorders

• Clinically defined genetic syndromes, such as:

  • Down's syndrome.

  • Prader-Willi syndrome.

  • Silver- Russell syndrome.

  • Noonan's syndrome.

  • Turner syndrome.

• Intrauterine growth restriction with failure to catch up, such as:

  • Maternal factors - eg, systemic disease, teratogenic medications, substance abuse.

  • Prematurity.

  • Placental dysfunction - eg, multiple pregnancy, placenta praevia, placental abruption.

• Congenital bone disorders such as:

  • Achondroplasia.

  • Hypochondroplasia.

  • Osteogenesis imperfecta.

Secondary growth disorders

• Endocrine:

  • Hypothyroidism.

  • Panhypopituitarism.

  • Hypothalamic or pituitary lesions (eg, trauma or tumour).

  • Growth hormone deficiency or insufficiency.

  • Growth hormone insensitivity: represents a wide diagnostic category, including a broad spectrum of defects. Low IGF-1 levels associated with normal or elevated growth hormone levels and the lack of IGF-1 response after growth hormone administration. Recombinant IGF-1 preparations may be used in treatment.⁴

  • Cushing's syndrome.

  • Precocious puberty.

  • Disorders of the growth hormone insulin-like growth factor axis.

• Metabolic:

  • Mucopolysaccharidoses.

  • Glycogen storage diseases.

• Diabetes mellitus (poor control).

• Chronic disease:

  • Cardiovascular disease.

  • Respiratory disease (eg, cystic fibrosis).

  • Haemoglobinopathies.

  • Renal disorders.

  • Malignancy.

  • Neurological (eg, hydrocephalus).

  • Juvenile arthritis.

• Malnutrition:

  • Poverty or neglect.

  • Inflammatory bowel disease.

  • Coeliac disease.

  • Bowel obstruction.

  • Enzyme deficiencies.

  • Chronic bowel infection.

  • Short bowel syndrome.

  • Anorexia nervosa.

  • Rickets.

• Psychosocial deprivation, including hyperphagic short stature syndrome.

• Medication: steroid therapy.

Assessment^{3 5}

History

• A comprehensive history starting in the prenatal and perinatal periods should be obtained. Emphases of the history include maternal health and habits during pregnancy, the duration of gestation, birth weight and length and growth pattern (centile charts if available).

• Obtaining the family history of growth patterns and direct measurement of the parents is crucial to determine the genetic potential for growth in the child. Ascertain timing of puberty in the parents.

• Ask about nutrition, including problems with feeding, appetite, food science, special diets or any other indication of inadequate nutrition.

• Consider any chronic disease and medication. Careful review of physical symptoms suggesting underlying chronic disease, such as breathlessness, diarrhoea. Ask about systemic symptoms, particularly of gastroenterological or neurological origin.

• Consider any signs of developmental delay. Ask about achievement of developmental milestones and any learning difficulty.

• Any indication of possible child abuse, including interaction of the child with the parent.

Examination

A thorough examination is essential to establish accurate height and weight and any indication of a possible underlying cause for short stature.

• Accurate measurement of height (using a calibrated stadiometer) and weight. Sitting as well as standing height are important in order to consider asymmetry and skeletal disproportion - eg, achondroplasia.

• A thorough physical examination helps differentiate abnormal growth patterns from normal variants and identifies specific dysmorphic features of genetic syndromes.

• Consider growth hormone deficiency from hypopituitarism - look for other features of pituitary hormone deficiency (eg, hypogonadism) and possible features of a pituitary tumour (eg, papilloedema and visual field defects).

• Consider any indications of other possible underlying causes - eg, Cushing's syndrome, chronic kidney disease, hypothyroidism or fetal alcohol syndrome.

• Look for features of Turner syndrome in girls.

• Look for features of skeletal causes - eg, rickets (craniotabes, bulbous wrists and bowing of the extremities), achondroplasia.

• Look for skin lesions such as café-au-lait spots or large haemangiomas.

Calculate expected final height

• The mid-parental height provides an estimation of the expected final height. If a child's height lies within the target centile range then their height is normal with regard to their genetic potential.

• A calibrated stadiometer should be used for measuring standing height and the heights of the parents should be accurately measured rather than rely on reported heights. The mid-parental height is unreliable if the parents' heights are very different.

• In a boy: Mid-parental height (cm) = (Father's height + (Mother's height + 13)) divided by 2.

• In a girl: Mid-parental height (cm) = ((Father's height - 13) + Mother's height) divided by 2.

Investigations⁵

Investigations indicated to confirm or exclude possible underlying causes are based on the clinical assessment. They may include:

• Blood tests:
  

  • FBC: anaemia blood dyscrasia and infections.

  • Renal function tests and electrolytes: renal disease and electrolyte abnormalities - eg, Bartter's syndrome, diabetes insipidus and other renal and metabolic disorders.

  • LFTs.

  • TFTs.

  • ESR and CRP: chronic inflammatory conditions.

• Urinalysis and urine pH level: renal tubular acidosis.

• Specific tests for suspected underlying or associated diseases - eg, coeliac disease, Cushing's disease, cystic fibrosis, growth hormone deficiency (IGF-I), vitamin D deficiency. Children with growth hormone deficiency may have delayed physical maturation, and therefore assessment of IGF-I must be interpreted in relation to pubertal status.⁶

• Bone age:
  

  • Bone age can help to predict the final adult height by estimating skeletal maturation from an assessment of the ossification of the epiphyseal centres.

  • The most widely used method is based on comparing a frontal radiograph of the left hand and wrist with standards from the Greulich-Pyle atlas.

  • Bone age is considered delayed if it is two standard deviations below the chronological age.

  • Bone age is usually normal for age in children with familial short stature. In children with CDGP the bone age corresponds with height age and is delayed (up to two standard deviations). In children with pathological short stature, the bone age is severely delayed (more than two standard deviations

  • Over-emphasis of bone age evaluation can be misleading if not used in the proper settings. The predictions do not apply to children with endocrine or bone pathologies affecting growth.⁷

• Dental age: can provide an indirect assessment of skeletal age. The eruption of primary and secondary teeth may be delayed for up to 1.3 years in children with growth hormone deficiency, up to 1.5 years in children with CDGP and more than two years in children with severe hypothyroidism.

Genetic evaluation⁸

If all biochemical studies show negative results and there is no particular phenotype, difficulties arise in determining the underlying cause of short stature. In this situation, genetic counselling and testing may be used, such as karyotyping for Turner syndrome, chromosomal microarray for chromosomal structural abnormalities, targeted gene panels for suspected genes (or accompanying symptoms), and exome sequencing for a broader genetic screening.

Referral³

Indications for referral include:

• Height: height fails to progress along the appropriate centile curve.

• Growth velocity: decreased growth velocity for age.

• Genetic potential: projected height varies from mid-parental height by more than 5 cm (2 in).

• Multiple syndromic or dysmorphic features: abnormal facies, midline defects, body disproportions.

• Bone age: delayed by more than two standard deviations.

• Any suspicion of an underlying cause of a secondary growth disorder (see above).

Short stature treatment and management³

Management of any identified underlying cause.

Growth hormone

• Growth hormone of human origin (somatotrophin) has been replaced by a growth hormone of human sequence (somatropin) which is produced using recombinant DNA technology.

• The National Institute for Health and Care Excellence (NICE) recommends that somatropin be used for the treatment of growth failure for children with growth failure who:⁹
  

  • Have growth hormone deficiency.

  • Have Turner syndrome.

  • Have Prader-Willi syndrome.

  • Have chronic kidney disease.

  • Are born small for gestational age with subsequent growth failure at 4 years of age or later.

  • Have short stature homeobox-containing gene (SHOX) deficiency.

• Treatment should be discontinued if:
  

  • Growth velocity increases by less than 50% from baseline in the first year of treatment.

  • Final height is approached and growth velocity is less than 2 cm total growth in one year.

  • Adherence is poor and cannot be improved.

  • Final height is attained.

Growth hormone therapy in children with idiopathic short stature seems to be effective in partially reducing the deficit in height as adults, although the magnitude of effectiveness is on average less than that achieved in other conditions for which growth hormone is licensed.¹⁰ Treated individuals remain relatively short when compared with peers of normal stature.¹⁰

Complications of short stature²

Children with short stature may be teased or bullied, with potential emotional and psychological consequences. This is a source of parental anxiety although, in general, studies are reassuring and suggest long-term complications are infrequent.¹¹ Because short stature causes anxiety and may prompt consultation it may draw attention to underlying conditions which will then get treated, with consequent improvement in general health.