Growth and Stature

This section focuses on normal physical growth and how to recognize deviations in growth to identify pathology. Each child’s height should be plotted on the appropriate growth chart. Growth charts for typical development are available from the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC). In the United States, the WHO growth charts are used for children younger than 24 months and the CDC growth charts are used for children age 2 years and older.

A patient’s current height and weight and their relation to the patient's previous growth pattern (height velocity and weight gain) are important to consider. A patient with preserved weight gain but a decrease in linear growth is more likely to have an endocrine disorder, whereas a patient with a decrease in weight percentile followed by a fall in linear growth is more likely to have an underlying chronic illness or gastrointestinal disorder. A careful history, review of systems, and physical examination are critical to help guide a differential diagnosis. For a more detailed discussion of childhood growth see Growth and Development in the Preventive/Well Child Care rotation guide and Puberty in the Adolescent Care rotation guide.

Assessment of Growth

Midparental height: Midparental height can be used to estimate a child’s genetic potential or target height. The height prediction is based on the sex-adjusted average of the biological parent’s heights according to the following formulas. The average difference in height between males and females is 13 centimeters.

Growth velocity: Growth velocity is defined as the rate of linear growth per year and can be calculated based on height measurements taken 3 to 12 months apart; measurements taken 6 to 12 months apart are ideal for improved accuracy. A decrease in linear growth velocity or the crossing of percentiles should raise clinical concern for a potential underlying medical issue.

Bone age: Assessment of bone age is based on a radiograph of the left wrist and hand and is used as an indicator of skeletal maturity by comparing the ossification pattern to a standard sex-specific reference (e.g., the Greulich and Pyle atlas). When compared with a patient’s chronological age, bone age can be delayed, advanced, or normal. A bone age greater than 2 standard deviations (SDs) above chronological age is considered advanced, and a bone age lower than 2 standard deviations below chronological age is considered delayed. The standard deviation for bone age varies by age and is generally given in the radiology report. Predicted adult height can be obtained from the bone age.

Body proportions: The upper segment to lower segment (US/LS) ratio is often used to determine body proportion. The lower segment is measured from the top of the pubic symphysis to the floor. The upper segment is calculated by subtracting the length of the lower segment from the patient’s height. An abnormal US/LS ratio indicates disproportionate growth and could indicate an underlying medical or genetic etiology.

Arm span: Arm span is measured as the distance between the tips of the middle fingers with the patient’s arms in the horizontal plane. Arm span is typically similar to or slightly less than height in early childhood and then, in later childhood and adulthood, exceeds linear height by a few centimeters. Increased arm span can indicate a genetic syndrome (e.g., Marfan syndrome).

Short Stature

Short stature is defined as height more than 2 SDs below the mean for sex and age and can be physiologically normal or caused by a wide range of disorders including:

• familial short stature

• constitutional delay of growth and puberty

• endocrine disorders

• systemic/chronic illness

• genetic syndromes

• central nervous system pathology (e.g., craniopharyngioma, other sellar or suprasellar mass)

Etiology

When investigating children with short stature, it is important to remember the “cannot miss” conditions for which poor growth velocity may be the first presenting sign. These include systemic illnesses, such as inflammatory bowel disease or malignancy, and central nervous system tumors affecting the pituitary, such as craniopharyngioma. Although the vast majority of children with short stature will be otherwise healthy, a careful evaluation is necessary for children with poor growth velocity to ensure these or other “cannot miss” conditions are identified.

Workup

General evaluation of short stature includes the following:

• bone age: delayed bone age could indicate constitutional delay of growth, growth hormone deficiency, hypothyroidism, or systemic illness

• complete blood count (CBC) with differential: anemia, myeloproliferative neoplasm, signs suggestive of IBD (anemia, thrombocytopenia)

• comprehensive metabolic panel: hepatic and kidney disease

• urinalysis (UA): kidney disease

• erythrocyte sedimentation rate, C-reactive protein: inflammatory bowel disease, autoimmune conditions

• celiac screen: celiac disease

• thyroid-stimulating hormone (TSH), free thyroxine (T4): hypothyroidism

• insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein (IGFBP-3): growth hormone deficiency

The following selective screening tests are indicated based on the clinical scenario:

• karyotype: Turner syndrome

• follicle-stimulating hormone (FSH), luteinizing hormone (LH): hypergonadotropic hypogonadism

• chloride sweat test: cystic fibrosis

• growth hormone stimulation testing: growth hormone deficiency

• brain MRI (usually for children with growth hormone deficiency on testing and/or poor growth velocity): central nervous system (CNS) lesion/pituitary malformation

• SHOX gene mutation: haploinsufficiency is a cause of short stature

• other specific testing based on clinical concern

Growth hormone: Growth hormone (GH) is secreted in a pulsatile manner, the majority overnight, and has a short half-life. Thus, a random level is likely to be low and not clinically useful. Growth factors such as insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) are measured instead, as they have long half-lives and are indirect measures of GH secretion. If GH deficiency is suspected, GH levels are measured using provocative GH stimulation testing.

Diagnosis

(Source: Short Stature in Childhood — Challenges and Choices. N Engl J Med 2013.)

Treatment

Recombinant human growth hormone (rhGH) therapy is FDA-approved for the conditions listed below. Most current forms of rhGH are given via injection nightly, although there are also long-acting formulations available that allow for weekly administration. Providers generally titrate dosing to growth velocity, IGF-1 levels, or both.

• growth hormone deficiency

• chronic renal insufficiency

• Turner syndrome

• Noonan syndrome

• Prader-Willi syndrome

• small for gestational age with failure of catch-up growth

• Short stature homeobox (SHOX) gene mutation

• idiopathic short stature (height >2.25 SDs below average and predicted adult height <59 inches for females or <63 inches for males)

Tall Stature

Tall stature is defined as a height >2 SDs above the mean height of the normal population. Most cases are attributed to familial tall stature or overnutrition, but tall stature may be associated with underlying pathological processes. A detailed history and physical exam are important to help guide evaluation. Physical exam findings of dysmorphic features or signs of acromegaly should raise concern for underlying pathology. No accepted standard of care exists for treating tall stature, per se; rather, it should be investigated as a possible sign of an underlying condition as described in the table below.