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Abstract
Short stature can be a cause of distress for children and families. It is not usually pathological, but it is important to identify treatable conditions. This article presents a systematic approach to the evaluation of a child with short stature, covering differential diagnoses, first line investigations and indications for treatment with growth hormone.
- Endocrinology
- Growth
- Paediatric Practice
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Introduction
A child is considered to have short stature if their height lies below the 2nd centile, which is roughly equivalent to two SDs below the population mean. In most cases, short stature is familial or caused by variants of normal growth patterns, but it is important to identify pathological causes of short stature such as a primary growth disorder or an underlying chronic illness, for example, coeliac disease/inflammatory bowel disease. Box 1 provides a list of causes of short stature, but this is by no means exhaustive and it is worth noting that endocrine abnormalities, such as growth hormone deficiency, are rare. A careful history, examination and serial measurements form the basis of any further investigations, and it is important to consider the phase of growth of the child, as different influences predominate at various ages during childhood. This is typically known as the infancy-childhood-puberty model of growth.1
Common causes of short stature
Normal variation (including familial and constitutional short stature)
Genetic/congenital/chromosomal conditions (see table 1)
Skeletal dysplasias (see table 1)
Chronic systemic disorders (eg, inflammatory bowel disease, coeliac disease, severe asthma)
Endocrine abnormalities (eg, untreated hypothyroidism, growth hormone deficiency)
Emotional/psychosocial deprivation
The newborn's size is determined by the intrauterine environment, and up to 3 years of age growth is predominantly under the control of nutritional influences. During this phase, typically in the first 18 months of life, the infant may have catch-up or catch-down growth, where the child reaches his or her genetically determined height centile.
During childhood (3 years to puberty), growth is predominantly determined by growth and thyroid hormones. During puberty, growth hormone and sex hormones act synergistically to result in the pubertal growth spurt.
For every child, it is important to consider the psychosocial circumstances, as it is well recognised that short stature can result from emotional deprivation or a pathological psychosocial environment.2 ,3
Clinical approach
History
The following features should be considered in the history:
Pregnancy history, including maternal health and medications, during pregnancy
Gestational age
Birth weight
Age when concerns first noted about growth
Subsequent patterns of growth
Nutritional history
Coexisting health problems and medication use
Family history, including heights and age of growth spurt and puberty of family members
Social history
Examination
A careful examination for signs of chronic illness or dysmorphic features is a crucial part of the assessment as there are several syndromes and conditions associated with short stature (see Otable 1).
Syndromes and conditions commonly associated with short stature
Examination includes careful auxology, with supine length used for children less than 2 years of age, and standing height used from the age of 2 years onwards where possible. This is a purely practical convention, as children over the age of 2 are more likely to be cooperative with standing heights, and the centile charts accommodate for the change in measurement from lying to standing. Sitting height and arm span may be used to assess body proportions.
Serial heights over a period of time are more meaningful than an isolated height measurement as they allow assessment of height velocity (ie, the rate of growth). Measurements more frequently than every 6 months may amplify any measurement errors.
Pubertal assessment is an important part of the examination, as growth is intimately related to stage of puberty. The growth spurt is seen towards the end of puberty in boys, typically around 14 years of age. Puberty tends to happen earlier in girls, with a peak height velocity usually occurring around 12 years of age. This is approximately 1 year before the onset of menstruation—the last feature of female pubertal development.
Delayed puberty results in a deceleration in height velocity prior to the pubertal growth spurt, which may cause concern; however, the final outcome is attainment of a normal or modest increase in adult height.4
In all patients, parental heights should be measured, and the mid-parental centile (MPC) is calculated. Using the guidance on the UK growth charts for children aged 2–18 years,5 the parent height comparator scale allows calculation of the MPC (see box 2). There is regression adjustment incorporated into this, meaning that children of very short or tall parents have a MPC nearer to average than expected.
Example calculation of mid-parental centile (MPC) (UK female 2–18 years growth chart)
To calculate the MPC, mark the mother's height on the left-hand scale and father's height on the right-hand scale. Draw a line between these two points. The MPC is where the drawn line crosses the central line.
Investigation and management
A suggested algorithm for the management of a child presenting with short stature is shown in figure 1 (prepubertal) and figure 2 (pubertal). As previously mentioned, it is important to consider pubertal status in relation to chronological age. Additional investigations would be needed if there were concerns about pubertal development, but these are beyond the remit of this article. It is important to recognise that not every child with a height below the 2nd centile needs investigation, and the algorithms merely offer guidance. The context and overall growth pattern of the child provides the most important guide to patient care.
Algorithm for management of prepubertal child with short stature.
Algorithm for management of pubertal child with short stature.
Note that a karyotype is mandatory in every female presenting with short stature, as some patients with Turner syndrome may have minimal dysmorphic features, and some cases (eg, mosaic Turner syndrome) may have signs of pubertal development.
If there are features suggestive of chronic illness, it is important that these are investigated and any illness treated, with a subsequent re-evaluation of growth. If there is continuing poor growth and height measurements dropping down the centile lines (growth deceleration) despite appropriate management, a referral to endocrinology may be appropriate to determine the need for further investigation (see figures 1 and 2).
Insulin-like growth factor-1 (IGF-1) is a peptide hormone that is the major mediator of growth hormone-stimulated somatic growth. Low levels can indicate growth hormone deficiency or insensitivity, but levels can also be low with poor nutritional status and associated conditions, such as hepatic failure, inflammatory bowel disease and renal failure. As such, results should not be interpreted in isolation. Furthermore, laboratory age-specific reference ranges should be used, as normal levels vary throughout childhood and adolescence.
Bone age reflects skeletal maturity and can be useful in the evaluation of growth disorders. A bone age is rarely useful for children under the age of 5. In children with normal growth, the bone age is usually equal to the chronological age, but an advance or delay of up to 18 months can be within the normal range. Large bone age discrepancies are not diagnostic, but can indicate a pathological cause. Significant bone age delays may be found in delayed puberty or an underlying chronic illness, whereas conditions of rapid growth, such as precocious puberty, can result in an advancement of bone age.
Treatment
In many instances, only reassurance is required. If an underlying chronic illness is found, it is essential that this is addressed first; this is particularly true in situations of poor nutrition, as even in the growth hormone deficient child, concomitant malnutrition will make growth hormone treatment less efficacious.
In the UK, growth hormone is licensed for use in children with short stature for a specific range of conditions (box 3),6 and treatment should always be initiated and monitored by a paediatrician with specialist expertise in managing growth hormone disorders.
UK licensed indications for use of growth hormone
Growth hormone deficiency
Turner syndrome
Prader–Willi syndrome
Chronic renal insufficiency
Born small for gestational age with subsequent growth failure at 4 years of age or later
Short stature homeobox-containing gene (SHOX) deficiency
Summary
When assessing a child with short stature, it is important to consider the wide range of factors affecting growth, including familial growth patterns, pubertal status, chronic illness, genetic disorders, social factors and endocrine disorders. It is important to try to distinguish between those who exhibit a normal variant of growth and require no therapy and those with an underlying pathological process.
Test your knowledge
Question 1 The following conditions are usually associated with short stature:
Noonan syndrome
Klinefelter syndrome
Chronic renal failure
Russell Silver syndrome
Growth hormone insensitivity
Question 2 The following conditions are licensed indications for growth hormone:
Turner syndrome
Prader–Willi syndrome
Noonan syndrome
Down syndrome
Chronic liver failure
Question 3 Appropriate first line investigations for a 3-year-old girl presenting with short stature include:
Karyotype
Thyroid function tests
Growth hormone stimulation test
Coeliac screen
Bone age
Growth hormone level
Question 4 Bone age:
Is usually delayed in precocious puberty
Is usually advanced in precocious puberty
Advance is associated with increased growth potential
Is usually delayed in untreated inflammatory bowel disease
Is usually delayed in obesity
Question 5 IGF-1 levels are often low in
Growth hormone deficiency
Growth hormone insensitivity
Inflammatory bowel disease
Obesity
Liver failure Answers to the questions are on page 203.
Footnotes
Contributors NA and SA contributed equally to the writing of this article. TM was involved in the review and amendments of the article. SA is to act as the guarantor for this article.
Competing interests None.
Provenance and peer review Commissioned; externally peer reviewed.