Shortstature

Short stature (dwarfism) in children is defined as a height that is at least two standard deviations (SDs) below the mean for children of the same age and sex. In adults, the condition is commonly defined as a height of 5 ft 1 in (155 cm) or less in men and 4 ft 10 in (147 cm) or less in women. Nonpathological variant short stature can be classified into three types: familial short stature (inherited short stature), constitutional delay of growth and puberty (an inherited pattern of short stature during childhood that is followed by a growth spurt during puberty, typically resulting in normal adult height), and idiopathic short stature (short stature in the absence of any metabolic, endocrine, or other diagnosis). These types of short stature are most often normal variants of growth and rarely affect a child's development beyond longitudinal growth. The pathological causes of short stature are diverse and include psychosocial circumstances as well as a variety of genetic, endocrine, and metabolic disorders, which may affect a child's development in other ways than longitudinal growth. Further diagnostic testing is 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 are made to determine bone age (skeletal age), based on which the adult size of the child can be predicted. Laboratory testing can help rule out any underlying condition. Treatment is rarely indicated in nonpathological short stature (e.g., if short stature does not represent a disability to the patient), while pathological short stature is treated according to the underlying condition and usually involves growth hormone supplementation.

DEFINITIONS

Short stature (dwarfism)
- Children: height of > 2 SDs below the mean for children of the same age, sex, and similar genetic background
- Adults: height of ≤ 4 ft 10 in (147 cm) for women and ≤ 5 ft 1 in (155 cm) for men ^[1]
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 the rate considered appropriate for sex and age.

Diagnosis

Physical examination findings
Growth rate
Family history of short stature
Midparental height (estimated adult height of a child calculated on the basis of parental height), calculated via the following formula:
- ♀ = [mother's height in cm + (father's height in cm - 13)]/2
- ♂ = [father's height in cm + (mother's height in cm + 13)]/2

Laboratory test

CBC, differential blood count, ESR
Thyroid function tests (see “Hypothyroidism”)
Renal function tests and urinalysis (in case of CKD and associated renal osteodystrophy)
Screening for GH deficiency (see “Hypopituitarism”)
Hormone profile (LH, FSH, estrogen/testosterone) for puberty status assessment
Karyotyping

Imaging tests

X-ray: used to determine an individual's bone age and height by comparing their x-ray images of the nondominant hand and wrist to those displayed in the standard bone development atlas
Cranial MRI: in suspicion of hypothalamic or pituitary tumors

Treatment

Management depends on the underlying cause:

Reassurance that low height is a normal variant (e.g., familial short stature) that does not require treatment
Discontinuation of growth-inhibiting medication (e.g., glucocorticoids)
Sex hormone substitution in children with delayed puberty and growth
GH supplementation (e.g., somatropin) in cases of GH deficiency, idiopathic short stature, and Turner syndrome
In case of primary severe IGF-1 deficiency: mecasermin (recombinant insulin-like growth factor)
Treatment of underlying conditions (see “Causes of short stature” above)

Causes

Behavioural and psychosocial circumstances

Maternal substance use	Nicotine: tissue hypoxia due to an increased carbon monoxide concentration and release of catecholamines Alcohol: underdevelopment of skeletal muscle cells and central nervous system (fetal alcohol syndrome) Cocaine: fetal hypoxia due to placental vessels vasoconstriction	Intrauterine growth retardation Low birth weight Skeletal anomalies
Psychosocial short stature	Emotional deprivation or stress that typically involves neglect, abuse, or a poor relationship between the patient and caregiver and leads to: Malnutrition Low GH levels	Poor growth or weight gain Poor record of school attendance and medical care Signs of child maltreatment Clinical and radiographic signs of abuse
Anorexia nervosa	Malnutrition	Low body weight Endocrine disorders CNS and cardiovascular abnormalities Recurrent bone fractures Fragile skin appendages

Systemic causes

Rheumatological diseases
Congenital hypothyroidism	Impaired skeletal development due to iodine deficiency	Congenital iodine deficiency syndrome (cretinism) Delayed skeletal age Intellectual disabilities
GH deficiencies	Impaired bone and muscle development	Growth delay Low bone density Muscle atrophy
Congenital adrenal hyperplasia	Rapid bone maturation due to increased androgen levels	Blood pressure disorders Hypoglycemia Adrenal crisis Failure to thrive
Glucocorticoid excess	Accelerated bone resorption Inhibited chondrogenesis	Cushingoid features Central obesity Moon facies Skin modifications Hypertension
Type 1 diabetes mellitus	Poor glycemic control and dysregulation of the hypothalamic-pituitary-somatotropic axis	Polyuria Polydipsia Polyphagia Recurrent infections
Juvenile idiopathic arthritis	Chronic inflammation of joints Side effects of long-term high-dose glucocorticoid therapy	Joints stiffening and deformation Growth delay Uveitis Rash Lymphadenopathy
Renal disorders
Chronic kidney disease (CKD)	Renal osteodystrophy due to: Low conversion of vitamin D to calcitriol Secondary hyperparathyroidism Hypophosphatemia Dysregulation of the GH/IGF-1 system Polyuria with mineral loss	Anemia of chronic kidney disease Rickets
Fanconi syndrome	Increased phosphaturia due to impaired tubular reabsorption of phosphate	Rickets/osteomalacia Polyuria Growth retardation
Metabolic disorders
Rickets	Defective growth plate and bone matrix mineralization due to vitamin D deficiency	Bowing of long bones Rachitic rosary Craniotabes Genu varum/valgus
Gastrointestinal disorders
Celiac disease/ Inflammatory bowel disease	Malabsorption due to chronic intestinal inflammation and damage	Abdominal pain Diarrhea Failure to thrive Extraintestinal inflammatory symptoms (e.g., arthritis, uveitis)
Chronic oxygen deficiency
Congenital heart defects	High energy requirements due to inappropriate gas exchange Decreased nutritional intake	Failure to thrive Signs of heart failure Exercise intolerance Cyanosis
Anemias	Tissue hypoxia and low metabolism rates	Pallor Exertional intolerance Hepatosplenomegaly
Immunological diseases
HIV infection	Chronic immunodeficiency associated with: Low dietary intake and altered metabolism Low IGF-1 levels and tissue insensitivity to IGF-1 Increased susceptibility to diarrhea	Anorexia, cachexia Malabsorption Severe infections and organ failure (e.g., HIV wasting syndrome) Growth failure
Severe combined immunodeficiency	Primary deficiency in B and T cells leading to Recurrent diarrheal infections Cachexia	Recurrent severe infections Diarrhea Thrush Failure to thrive
Other causes of short stature
Neoplasms	GH deficiency due to: Mass effect of hypothalamic or pituitary tumors Hypothalamic or pituitary radiation Primary hypothyroidism due to radiation Nausea and vomiting as a result of radiotherapy and chemotherapy	Weight loss Fatigue Anemia Fever

Genetic causes

Pathological short stature
Familial short stature	Hereditary short stature Most common cause of proportionate short stature	Normal development Skeletal age consistent with chronological age
Constitutional growth delay	Inherited type of developmental delay (autosomal dominant, recessive, or X-linked trait) Delay in pulsatile hypothalamic GnRH release	Temporary delay in growth and onset of puberty X-ray shows a delayed bone age (less than the individual's chronological age) Delayed onset of puberty, but no treatment is needed Reassuring the child and parents is sufficient. Catch-up growth eventually occurs. Individual reaches a normal adult height.
Idiopathic short stature	Diagnosis of exclusion in the absence of an underlying condition	Height of ≤ 2 SDs below the mean for age that cannot be explained by inheritance or pathological processes.
Laron syndrome	Tissue insensitivity to growth hormone (GH) due to GH receptor mutation (leads to ↓ linear growth)	Microcephaly Prominent forehead Saddle nose Hypoglycemia Delayed puberty Small genitalia Hormones: ↑ GH and ↓ IGF-1
Skeletal dysplasias	Impaired osteogenesis	See the section on “Skeletal dysplasias” below.
Turner syndrome	Loss of one SHOX gene copy from the missing X chromosome	Skeletal abnormalities Gonadal dysgenesis Congenital cardiovascular defects
Down syndrome	Possibly due to selective IGF-1 deficiency	Craniofacial dysmorphia Skeletal abnormalities Developmental delay Obesity
Williams syndrome	Loss of several genes from chromosome 7	Cognitive impairment Elfin-like facies Cardiovascular abnormalities
Cystic fibrosis	Defective chloride channels → secretion of hyperviscous mucous → blockage of exocrine glands → chronic mucosal inflammation	Malnutrition Failure to thrive Chronic infections
Pseudohypoparathyroidism (Albright hereditary osteodystrophy)	Impaired bone growth due to PTH resistance	Obesity Round face Short neck Brachydactyly
McCune-Albright syndrome	Accelerated bone maturation associated with early onset of puberty	Polyostotic fibrous dysplasia Café au lait spots Precocious puberty