Differentials
Common
Familial short stature (genetic short stature)
History
typically born adequate for gestational age; steady growth below the 5th percentile; final height appropriate for short target height; puberty usually not delayed
Exam
normal examination; proportionate short stature; appropriate weight gain for age
1st investigation
- no initial test:
clinical diagnosis
Other investigations
- bone age:
normal (same as chronological age)
Constitutional delay of growth and development
History
more frequent in boys; growth deceleration during the first 2 years followed by a normal growth velocity with acceleration late in adolescence; final height close to the target height; late pubertal development in either parent[12]
Exam
usually normal although these children are frequently relatively thin and sexually immature for age; proportionate short stature[12]
1st investigation
- bone age:
delayed by 1-2 years
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Other investigations
Idiopathic short stature
History
short but otherwise healthy; no weight deceleration; normal target height
Exam
normal; proportionate short stature; puberty starts and proceeds normally
1st investigation
Other investigations
- growth hormone (GH) stimulation tests:
normal; peak GH level >10 micrograms/L (>10 nanograms/mL)
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Small for gestational age (SGA) without catch-up growth by 2 years of age
History
intrauterine growth restriction without a particular syndrome; SGA at birth
Exam
usually normal; proportionate short stature
1st investigation
- no initial test:
clinical diagnosis
Other investigations
Uncommon
Growth hormone (GH) deficiency
History
hypoglycaemia or micropenis at birth; adequate for gestational age; growth deceleration occurs after the age of 2 years; may be accompanied by other pituitary deficiencies
Exam
striking growth retardation; proportionate short stature; 'cherubic' appearance (looking much younger than their stated age with a low muscle-to-fat ratio); boys may have micropenis; midline defects such as a single incisor, cleft lip/palate, midfacial hypoplasia in congenital GH deficiency
1st investigation
Other investigations
- GH stimulation tests:
low; peak GH level <10 micrograms/L (<10 nanograms/mL) on two occasions
More - MRI brain:
may be normal or reveal a pituitary abnormality such as an ectopic posterior pituitary or central nervous system (CNS) malignancy
More - full pituitary hormone assessment:
may reveal other pituitary hormone deficiencies
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Hypothyroidism
History
fatigue, cold intolerance, dry skin, hair loss, constipation, lethargy, and weight gain; growth deceleration can occur at any age; newborn screening programmes may detect congenital primary hypothyroidism; acquired autoimmune hypothyroidism more common in girls
Exam
proportionate short stature; facial coarsening, non-pitting oedema; growth deceleration in the presence of increased weight gain; bradycardia, hypothermia in severe cases
1st investigation
Other investigations
Cushing syndrome
History
recent excessive weight gain in a cushingoid distribution coupled with growth failure, easy bruising, new striae, mood swings; history of asthma or inflammatory conditions that are treated with corticosteroids; more subtle changes and growth deceleration with inhaled corticosteroids
Exam
increased weight for height ratio, proportionate short stature, acne, obesity with cushingoid features (e.g., buffalo hump), hirsutism, violaceous striae, hypertension
1st investigation
- late-night salivary cortisol:
elevated
More
GH insensitivity (Laron syndrome)
History
severe short stature with normal birth weight and length; history of hypoglycaemia at birth
Exam
proportionate short stature with a good weight-to-height ratio
1st investigation
Other investigations
- basal GH:
normal or elevated
Craniopharyngioma
History
headache, diplopia, symptoms of other pituitary hormone deficiencies (e.g., polyuria, delayed puberty); past history may include surgery/radiotherapy for craniopharyngioma
Exam
proportionate short stature, papilloedema, vision loss
1st investigation
Other investigations
Turner syndrome
History
may present primarily with short stature; history of lymphoedema at birth; congenital heart or renal disease, delayed or arrested puberty, hearing loss, and learning difficulties
Exam
may be normal except for proportionate short stature or presence of webbed neck, low posterior hairline, broad chest with widely spaced nipples, hypertelorism, posteriorly rotated ears, increased carrying angle, may have a heart murmur
1st investigation
- karyotype:
45 XO, 46/45 XX/XO, partial X chromosome deletion or circular X chromosome
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Other investigations
- serum follicle-stimulating hormone (FSH) and anti-Müllerian hormone (AMH):
FSH-(abnormally) high; AMH-(abnormally) low
More - ultrasound abdomen/pelvis:
ovarian dysgenesis; may have renal abnormalities
- echocardiogram:
aortic valvular abnormalities or coarctation of the aorta
Noonan syndrome
History
some present only with short stature; others have dysmorphic features, congenital heart disease, and learning difficulties
Exam
may be normal except for proportionate short stature or have webbed neck, low posterior hairline, low-set ears; may have a heart murmur
1st investigation
- no initial test:
clinical diagnosis
More
Other investigations
- genetic testing:
may be positive for a mutation in the PTPN11 gene; other characteristic mutations include SOS1, RAF1, RIT1, RASA2, LZTR1, SHOC2, KRAS, NRAS, BRAF, and MAP2K1
More - echocardiogram:
pulmonary valvular abnormalities
Russell-Silver syndrome
History
born small for gestational age; feeding difficulties, increased sweating, history of hypoglycaemia
Exam
small triangular face, asymmetry, clinodactyly; proportionate short stature
1st investigation
- no initial test:
clinical diagnosis
Other investigations
- genetic testing:
may reveal maternal uniparental disomy for chromosome 7 (mUPD7) or loss of methylation at 11p15
Trisomy 21
History
diagnosis generally confirmed at birth due to dysmorphic features; advanced maternal age; developmental delay, congenital cardiac or gastrointestinal (GI) abnormalities
Exam
proportionate short stature, hypotonia, dysmorphic features (e.g., large tongue, upward slant of palpebral fissures, round face, brachycephaly, simian palmar crease, and hypotonia); may have a heart murmur
1st investigation
- karyotype:
trisomy 21
More
Other investigations
- echocardiogram:
increased incidence of congenital defects such as atrioventricular septal defect, ventricular septal defect
Prader-Willi syndrome (PWS)
History
obesity, hyperphagia, learning difficulties
Exam
proportionate short stature, small hands and feet, marked obesity
1st investigation
- DNA methylation testing:
no paternal allele at 15q11-q13
More
Other investigations
DiGeorge syndrome (velocardiofacial syndrome)
History
dysmorphic features at birth; feeding difficulties due to cleft palate and oesophageal fistulas; learning difficulties
Exam
cleft palate, heart murmur, proportionate short stature
1st investigation
- fluorescence in situ hybridisation:
1 copy of probe per cell confirms 22q11.2 deletion
More
Other investigations
- karyotype:
may detect other genetic abnormalities
More - echocardiogram:
tetralogy of Fallot, interrupted aortic arch, ventricular septal defect, and persistent truncus arteriosus are the commonest congenital heart defects
- bone profile:
hypocalcaemia and hypoparathyroidism
Coeliac disease
History
diarrhoea, weight loss, abdominal pain[48]
Exam
proportionate short stature, poor weight for height ratio, pallor, abdominal distension, muscle wasting
1st investigation
- immunoglobulin A-tissue transglutaminase (IgA-tTG):
titre above normal range for laboratory; however, a normal titre does not exclude coeliac disease, as seronegative coeliac disease occurs in a minority of patients
- endomysial antibody:
elevated
More - FBC:
anaemia, elevated or low WBC and platelet count
More - complete metabolic panel:
elevated liver enzymes, low albumin
More
Other investigations
Cystic fibrosis (CF)
History
recurrent chest infections, malabsorption, diarrhoea, poor weight gain
Exam
proportionate short stature, poor weight for height ratio, pallor, muscle wasting, abnormal lung examination and tachypnoea
1st investigation
Other investigations
- genetic analysis:
mutations in the CFTR gene
Asthma (moderate or severe)
History
recurrent cough, wheeze, inhaler therapy, eczema, frequent admissions and/or corticosteroids
Exam
proportionate short stature, poor weight for height ratio, abnormal lung examination and tachypnoea
1st investigation
- no initial test:
clinical diagnosis
Chronic heart disease (congenital or acquired)
History
fatigue, dyspnoea, poor feeding, chest pain, exercise intolerance, cyanosis; previous cardiac surgery
Exam
proportionate short stature, poor weight for height ratio, pallor, heart murmur, tachycardia, sternal scars
1st investigation
- echocardiogram:
often normal, but may reveal cardiac defect or poor cardiac function
More
Other investigations
Diabetes mellitus
History
polyuria, polydipsia, poor weight gain, history of frequent urinary infections, poor appetite; on insulin therapy with poor compliance
Exam
proportionate short stature, poor weight for height ratio, injection site scars
1st investigation
- HbA1c:
≥48 mmol/mol (6.5%)
More
Other investigations
Chronic kidney failure
History
frequent urinary infections, slow weight gain, poor appetite, haematuria, proteinuria; family history of early kidney disease
Exam
proportionate short stature, poor weight for height ratio, pallor, oedema, hypertension
1st investigation
Other investigations
Juvenile idiopathic arthritis (JIA)
History
joint pains, fever
Exam
proportionate short stature, limping, joint swellings, rash
1st investigation
Other investigations
Crohn's disease
History
abdominal pain, diarrhoea, joint pains, bloody stools
Exam
proportionate short stature, poor weight for height ratio, pallor, abdominal distension and tenderness, skin rashes, arthritis, anal involvement, fistulae
1st investigation
Other investigations
Ulcerative colitis
History
abdominal pain, diarrhoea, joint pains, bloody stools[49]
Exam
poor weight for height ratio, proportionate short stature, pallor, abdominal distension and tenderness, skin rashes, arthritis, sparing of anal involvement
1st investigation
Other investigations
Malignancy
History
history of any malignancy; poor feeding; fatigue, low-grade fever, pain; patient may already be on chemotherapy or radiotherapy
Exam
poor weight for height ratio, proportionate short stature, pallor, abnormal systemic examination
1st investigation
Other investigations
Renal tubular acidosis
History
poor weight gain, poor appetite, haematuria, renal pain
Exam
poor weight for height ratio, pallor, proportionate short stature
1st investigation
Other investigations
Rickets
History
bone pains, dental problems, tetany, muscle weakness, poor diet, or decreased exposure to sunlight
Exam
bony deformities (genu varum, genu valgum, rachitic rosary), open fontanelle, disproportionate short stature (in severe cases)
1st investigation
- bone profile:
hypocalcaemia, hypophosphataemia (in nutritional rickets), elevated alkaline phosphatase
- x-ray wrist:
decreased mineralisation
Other investigations
Skeletal dysplasias (e.g., achondroplasia, hypochondroplasia, osteogenesis imperfecta)
History
recurrent fractures without major trauma in osteogenesis imperfecta; recurrent otitis media with hydrocephalus in achondroplasia; family history of bone dysplasia
Exam
disproportionate short stature, bone deformities, blue sclera (in osteogenesis imperfecta), kyphoscoliosis (in achondroplasia), open fontanelle
1st investigation
- skeletal survey:
abnormal
More
Other investigations
Spinal disorders (irradiation, surgery, congenital deformities)
History
may have known congenital deformity such as hemivertebrae; previous malignancy treated with irradiation or spinal surgery
Exam
disproportionate short stature with a shorter upper segment
1st investigation
- x-ray spine:
reveals deformity
Other investigations
Psychosocial deprivation (abuse, neglect, starvation, institutionalisation)
History
abuse, neglect, institutionalisation, unstable home environment, recurrent fractures, poor weight gain
Exam
signs of neglect (nappy rash, sores, poor hygiene), signs of abuse (bruises, fractures), signs of malnutrition (muscle wasting, decreased subcutaneous fat), retinal haemorrhages if the child has been shaken violently, proportionate short stature
1st investigation
- no initial test:
clinical diagnosis
More
Other investigations
Anorexia nervosa
History
poor weight gain, low calorie count, abnormal eating patterns, family history of eating disorders, history of ADHD medications
Exam
low weight for height ratio, proportionate short stature, little subcutaneous fat
1st investigation
- clinical history:
detailed history using criteria such as those of the DSM-5-TR can confirm diagnosis
- FBC:
may have anaemia, mild leukopenia, or thrombocytopenia
- basic metabolic panel:
may be deranged
- thyroid function tests:
low T3, normal T4, normal TSH
More
Other investigations
Bulimia nervosa
History
poor weight gain, low calorie count, bingeing followed by purging, abnormal eating patterns, family history of eating disorders, history of ADHD medications
Exam
low weight for height ratio, proportionate short stature, little subcutaneous fat
1st investigation
- clinical history:
detailed history using criteria such as those of the DSM-5-TR can confirm diagnosis
- FBC:
may have anaemia
Other investigations
Fetal alcohol syndrome
History
antenatal ingestion of alcohol in mother, poor social history, small for gestational age at birth, learning difficulties
Exam
craniofacial and CNS abnormalities in the presence of proportionate short stature
1st investigation
- no initial test:
clinical diagnosis
Other investigations
Stimulant medications for ADHD
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