Short stature is defined as height that is two standard deviations below the mean height for age and sex (less than the 3rd percentile) or more than two standard deviations below the mid-parental height. The child’s rate of growth called growth velocity is important.. 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. A downward growth trend suggests a slowdown in growth and possibly a growth problem. The causes of short stature can be divided into three broad categories:
- Familial short stature
- Constitutional delay of growth and development
- Chronic disease, including malnutrition and genetic disorders
In some cases, short stature or slow growth is the initial sign of a serious underlying disease in an otherwise healthy child.
Causes of short stature
Most children with short stature will have constitutional delay of growth and puberty (CDGP) or familial short stature. Endocrine diseases are rare but important causes of short stature, as early identification and early intervention results in normal adult height.
Familial short stature, constitutional delay in growth and puberty (CDGP)
Intrauterine growth restriction:
Congenital, eg Silver-Russell syndrome, Prader-Willi syndrome
Poverty or neglect, inflammatory bowel disease, celiac disease, bowel
obstruction, enzyme deficiencies, chronic bowel infection
Cardiovascular disease, respiratory disease, haemoglobinopathies, kidney disease, renal tubular acidosis, malignancy, neurological (eg hydrocephalus).
Chondrodysplasias, osteogenesis imperfecta, rickets, achondroplasia, hypochondroplasia
Turner’s syndrome, trisomy syndromes
Hypothyroidism, growth hormone deficiency or insufficiency, Growth hormone resistance(Laron’s dwarfism), panhypopituitarism, Cushing’s syndrome, pseudohypoparathyroidism, congenital adrenal hyperplasia
Mucopolysaccharidoses, glycogen storage disease
Steroids (iatrogenic cushing’s syndrome)
Obtaining the family history of growth patterns and direct measurement of the parents is crucial to determine the mid-parental height and the genetic potential for growth in the child. Short stature can also be the sign of a wide variety of pathological conditions or inherited disorders when it results from growth failure(achondroplasia) or premature closure of the epiphysial growth plates(congenital adrenal hyperplasia).
Specific history should be focused on
- Antenatal events: Maternal nutrition, health habits, anemia, pregnancy induced hypertension, history of poor growth in utero
- Natal history: duration of gestation, birthweight and length, prolonged jaundice(congenital hypothyroidism, congenital hypopituitarism), neonatal hypoglycemia, floppiness with feeding difficulty(Prader-Willi Syndrome) and puffy hands and feet(Turner syndrome).
- Family history of consanguinity, similar condition in a family member, height and puberty in siblings and parents
- Consider any chronic disease and medications like steroids. Careful review of physical symptoms suggesting underlying chronic disease, such as breathlessness, diarrhea, recurrent fever, dysuria, hematuria, jaundice etc
- Any indication of possible child abuse, including interaction of the child with the parent.
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 is essential. Sitting as well as standing height are important in order to consider asymmetry and skeletal disproportion (disproportionate short stature – achondroplasia).
A thorough physical examination helps differentiate abnormal growth patterns from normal variants and identifies specific dysmorphic features of genetic syndromes.
- Growth hormone deficiency from hypopituitarism: other features of pituitary hormone deficiency, eg Hypogonadism(micropenis), and features of a pituitary tumour, eg papilloedema and visual field defections
- Consider any indications of other possible underlying causes, eg Cushing’s syndrome, chronic kidney disease, hypothyroidism or fetal alcohol syndrome
- Features of Turner’s syndrome in girls if present are diagnostic
- Skeletal causes, eg achondroplasia and rickets (craniotabes, bulbous wrists and bowing of the extremities)
Calculate expected final adult 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. Target centile range: ± 10 cm around the mid-parental height.
In a girl: Mid-parental height (cm) = ((Father’s height – 13) + Mother’s height) divided by 2. Target centile range: ± 8.5 cm around the mid-parental height.
Investigations are indicated to confirm or exclude possible underlying causes based on the clinical assessment. Initial tests include
- Hemogram and ESR
- Renal function tests and electrolytes(sodium, potassium, bicarbonate)
- Serum protein, Liver function test
- Urinalysis and urine pH
- Karyotyping (particularly considering Turner’s syndrome) should be performed in all girls with short stature. FSH is done if girl is less than 2 years of age or more than 8 years of age.
- Anti-Tissue transglutaminase antibody to rule out celiac disease
- Specific tests for suspected underlying or associated diseases, eg, Cushing’s
- disease, cystic fibrosis, growth hormone deficiency, hypothyroidism, vitamin D deficiency
- Chest X-ray PA view, Skull X-ray lateral, X-ray left hand with wrist AP(for bone age)
Bone age can help to diagnose the cause of short of stature like CDGP, familial short stature and endocrine disorders and to estimate the final adult height. The most widely used methods are based on comparing a radiograph of the left hand and wrist with standards from the Greulich-Pyle atlas or by Tanner-Whitehouse method.
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 constitutional delay of growth and puberty (CDGP) the bone age corresponds with height age and is delayed (up to two standard deviations). In children with pathological short stature(hypothyroidism), the bone age is severely delayed (more than two standard deviations).
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 constitutional delay of growth and puberty, and more than two years in children with severe hypothyroidism.
Management should be directed towards identification of any underlying systemic cause.
Example: Thyroxine therapy in a child with hypothyroidism as monitored by Endocrinologist often results in normal final adult height
Growth hormone is produced using recombinant DNA technology currently and Inj.Growth Hormone (somatropin) is currently approved for use in children for the treatment of growth failure who:
- Have growth hormone deficiency
- Have Turner’s 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.
Mecasermin, a recombinant human insulin-like growth factor-I (rhIGF-I), is licensed to treat growth failure in children and adolescents with severe primary insulin-like growth factor-I deficiency.