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Short Stature: History Taking and Differential Diagnoses

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Overview

Short stature is defined as a heigh that is ≥2 standard deviations below the mean for age and sex within a population (below the 2.5th percentile). Its causes can range from a constitutional delay of growth and puberty to more severe conditions.

Causes

Idiopathic

No identifiable cause of short stature is present. Causes include:

  • Familial short stature
  • Constitutional delay of growth and puberty
  • Idiopathic short stature

Primary growth disorders

There are problems with the growth plates themselves. Causes include:

Secondary growth disorders

Disease processes lead to changes in the growth plates. Causes include:

Assessment

Overview

A full and thorough Paediatric History should be taken. A growth chart should be plotted and a general examination looking for dysmorphic features should be performed. Other examinations are based on the history and suspected differential diagnoses.

The mid-parental height may be calculated to estimate the child’s expected final height:

  • Boy: mid-parental height (cm) = (Father’s height + (Mother’s height + 13)) divided by 2.
  • Girl: mid-parental height (cm) = ((Father’s height – 13) + Mother’s height) divided by 2.

It may be helpful to divide patients into:

  • If dysmorphic features are present, which can further be divided into:
    • Upper and lower segments are proportionate
    • Upper and lower segments are not proportionate
  • If dysmorphic features are absent, which can further be divided into:
    • Increased weight compared to height
    • Decreased/normal weight compared to height (faltering growth, failure to thrive)

Referral and Investigations

Referral

Refer to secondary care if any of the following are present:

  • Failure of height increase and decreased growth velocity for age
  • Projected height varies by more than 5 cm
  • Dysmorphic features or multiple features that suggest the presence of an underlying syndrome
  • Bone age that is delayed by >2 standard deviations
  • Any suspicion of an underlying secondary cause

Overview

When suggesting investigations in an OSCE, the BOXES (Blood tests, orifice tests, x-rays, ECGs, special tests) mnemonic is useful for deciding the order of investigations. Some investigations may include:

  • Blood tests:
    • Full blood count (FBC):
      • May show anaemia
      • May show blood cell lineage abnormalities
    • Urea and electrolytes (U&Es):
      • May identify renal disease
    • Liver function tests (LFTs):
      • May identify liver disease
    • Thyroid function tests (TFTs):
      • To screen for hypothyroidism
    • Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP):
      • Non-specific markers of inflammation, may be elevated
    • Coeliac screen:
      • May be positive
    • Bone profile and vitamin D:
      • May identify metabolic bone diseases (e.g. rickets)
    • HbA1c and/or blood glucose:
      • For diabetes mellitus
  • Orifice tests:
    • Urinalysis and urinary pH:
    • Faecal calprotectin:
      • To screen for inflammatory bowel disease
  • X-rays:
    • X-ray of the wrist:
      • May be used to asses bone age – if ≥2 standard deviations below the expected value for their age, there is a delay
  • Special tests:
    • Echocardiography:
      • For congenital heart disease
    • Serum insulin-like growth factor 1 (IGF-1):
      • For growth hormone deficiency
    • Cortisol and dexamethasone suppression tests:
      • For Cushing’s syndrome
    • Sweat test:
      • For cystic fibrosis
    • Neuroimaging:
      • For pituitary tumours and craniopharyngiomas
    • Genetic testing and karyotyping:
      • For genetic disorders

Differential Diagnoses: Idiopathic

Familial short stature

  • No problems before, during, or after pregnancy, born at normal weight for gestational age
  • Height and weight growth is steady and not faltering
  • Parents are short and there is a family history of short height
  • Diagnosis is clinical, however, bone age may be calculated and is normal.

Constitutional delay in growth and puberty

  • More common in boys, there is a family history of delayed puberty in one or both parents
  • Usually growth deceleration for around 1-2 years followed by normal puberty and growth
  • Physical examinations are normal but may show proportionate short stature and sexual immaturity
  • Some investigations include:
    • Bone age:
      • Delayed by 1-2 years

Idiopathic short stature

  • Proportional short stature with no other abnormalities and normal puberty
  • All tests are normal

Differential Diagnoses: Endocrine Disorders

Growth hormone deficiency

  • Short stature, associated with obesity, appearing younger than their stated age, reduced muscle:fat ratio
  • Males may have a micropenis
  • In more severe cases, there may be ‘cherubism’ – rounded face, forehead prominence, and maxillary hypoplasia
  • Some investigations include:
    • Bone age:
      • Delayed
    • IGF-1:
      • Low
    • Growth-hormone stimulation tests:
      • Low
    • Pituitary hormone profile:
      • May identify other hormone abnormalities
    • MRI brain:
      • May identify pituitary absence/tumour

Hypothyroidism

  • Fatigue, lethargy, dry skin, cold intolerance, weight gain and obesity, constipation, poor growth, non-pitting oedema
  • The newborn blood spot test screens for congenital primary hypothyroidism
  • Some investigations include:
    • TFTs:
      • Thyroid-stimulating hormone (TSH): increased
      • T3 and T4: decreased

Cushing’s syndrome

  • Facial plethora, facial fullness (‘moon face’), truncal obesity, purple striae, acne, depression, proximal muscle weakness, hirsutism
  • Corticosteroid use may be present (e.g. for induction of remission in inflammatory disease)
  • Bitemporal hemianopia may be present in Cushing’s disease 
  • Some investigations include:
    • 24-hour urinary free cortisol:
      • Elevated
    • Overnight dexamethasone suppression tests:
      • Helps with localising underlying cause

Precocious puberty

  • Puberty occurs before 8 years old in girls and 9 years old in boys
  • May be idiopathic or due to an underlying condition (e.g. tumours affecting the hypothalamic-pituitary-axis or gonadal tumours secreting excess sex hormones)
  • Some investigations include:
    • Bone age:
      • Advanced
    • Early morning FSH and LH:
      • May be elevated or low
    • Sex hormone testing:
      • Testosterone/oestrogen may be elevated
    • Pelvic ultrasound:
      • To assess pelvic organs (e.g. ovaries) in girls
      • May show cysts or tumours
    • Adrenocorticotrophic hormone (ACTH) stimulation test:
    • MRI brain:
      • May show pituitary tumours
    • Genetic tests:
      • Considered if a genetic disorder is suspected

Pituitary tumour or craniopharyngioma

  • Headaches that vary with posture (e.g. coughing, sneezing, straining, leaning forward), nocturnal headaches that prevent sleep or wake the patient up, headaches that are present upon waking
  • There may be visual field defects:
    • Bitemporal hemianopia affecting the upper quadrants more – pituitary tumour
    • Bitemporal hemianopia affecting the lower quadrants more – craniopharyngioma
  • Some investigations may show:
    • CT/MRI brain:
      • Identifies tumour
    • Pituitary hormone testing:
      • May identify deficiencies in hormones

Differential Diagnoses: Chronic Illness

Congenital heart disease

  • Features depend on the underlying cause: chest pain, shortness of breath, poor feeding, cyanosis, syncope, palpitations, previous heart surgery
  • Heart murmurs, extra heart sounds, arrhythmias, heaves and thrills may be present
  • An infant with faltering growth and absent femoral pulses suggests coarctation of the aorta
  • Some investigations include:
    • ECG:
      • May identify arrhythmia, ventricular hypertrophy etc.
    • Echocardiography:
      • Usually diagnostic for congenital heart disease

Cystic fibrosis

  • Meconium ileus – failure to pass meconium within 48 hours of life
  • Recurrent chest infections, chronic cough, thick sputum
  • Steatorrhoea, poor weight gain, abdominal pain and bloating
  • Nasal polyps, delayed puberty
  • Some investigations include:
    • Newborn blood spot testing:
      • Performed on all children shortly after birth
    • Sweat test:
      • The gold standard
      • Show abnormally high sweat chloride (>60 mmol/L)
    • Genetic testing;
      • May be performed antenatally via amniocentesis of chorionic villous sampling

Chronic kidney disease

Juvenile idiopathic arthritis

  • Seen in children <16 years old and persists for >6 weeks
  • Oligoarticular form is most common – <5 joints affected
  • Joint pain, swelling, and stiffness – usually asymmetric and large joints (knees, ankles, wrists, and elbows)
  • In the systemic-onset form, a salmon-pink rash and lymphadenopathy may be seen
  • Some investigations include:
    • Full blood count (FBC):
      • May show anaemia
    • ESR:
      • May be elevated

Malignancy

  • Constitutional symptoms – fever, night sweats, weight loss, lethargy
  • The patient may be undergoing treatment (e.g. chemotherapy)

Poorly controlled diabetes mellitus

  • It is important to note that the incidence of T1DM and DKA is increasing in children and young people. Always suspect them in a young child who is drinking more than usual, having more wet nappies, yet still losing weight. Glucose in the urine of a child should immediately warrant a referral to secondary care for management.
  • Polyuria, polydipsia, recurrent urinary tract infections, anorexia, poor weight gain
  • Some investigations include:
    • HbA1c:
      • Elevated

Differential Diagnoses: Malnutrition

Rickets

  • There may be poor sunlight exposure, malabsorption, chronic kidney disease
  • Painful bones and joints
  • Genu varum or genu valgum
  • Painful wrist swelling, painful swelling of costochondral junctions (rachitic rosary), craniotabes (skull softening, frontal bossing, delayed fontanelle closure), delayed tooth eruption
  • Some investigations include:
    • Serum 25-hydroxyvitamin D levels:
      • Low
    • Serum calcium and phosphate:
      • Calcium – decreased
      • Phosphate – may be decreased
    • Serum parathyroid hormone (PTH):
      • May be elevated
    • X-ray of long bones:
      • May show a widening of the growth plate

Child maltreatment

  • See Child maltreatment
  • Scavenging, stealing, hoarding, or hiding food
  • Inconsistent/inappropriate explanations for the child’s presentation (e.g. fractures in non-mobile infants)
  • Associated injuries and bruising, delay in presentation, frequent attendances to hospital, recurrent trauma
  • Features of neglect (e.g. unhygienic), behaviours inconsistent with the child’s age/development (e.g. fearful and withdraw, overly friendly, overly comforting in distress, inappropriate sexual behaviour)

Coeliac disease

  • Recurrent, crampy abdominal pain, diarrhoea, may have steatorrhoea
  • There may be associated distention, dermatitis herpetiformis
  • Failure to thrive, underweight, short stature
  • There may be a personal/family history of autoimmune disease including type 1 diabetes and hypothyroidism
  • Some investigations include:
    • Full blood count (FBC):
      • May show anaemia
    • Coeliac disease screening:
      • May be positive
    • Endoscopy and jejunal biopsy:
      • Diagnostic

Crohn’s disease

  • A history of chronic diarrhoea may be present
  • There may be associated fatigue, weight loss, and fever
  • An ileocaecal (right lower quadrant) mass may be present on exam
  • Oral ulcers and perianal disease (e.g. skin tags, fistulae, abscesses etc.) may be
  • present
  • Some investigations include:
    • FBC:
      • Anaemia may be seen
    • ESR/CRP:
      • ESR/CRP may be elevated
    • Faecal calprotectin:
      • May be positive

Ulcerative colitis

  • A history of chronic diarrhoea may be present – more commonly bloody than in Crohn’s disease
  • Faecal urgency and tenesmus may be present
  • Extra-intestinal features (e.g. joint pain) may be present
  • Some investigations include:
    • FBC:
      • Anaemia may be seen
    • ESR/CRP:
      • ESR/CRP may be elevated
    • Faecal calprotectin:
      • May be positive

Anorexia nervosa

  • Fear of gaining weight or becoming fat even if underweight
  • Preoccupations relating to food (e.g. calorie counting or reading nutritional information etc.)
  • Disturbed body image and disproportionate concern about weight and body shape
  • There may be consequences of low weight such as amenorrhoea, orthostatic hypotension, fatigue and weakness etc. 

Bulimia nervosa

  • Recurrent episodes of binge eating and a sense of lack of control during episodes
  • Purging behaviours after binge eating (e.g. self-induced vomiting, laxatives, fasting, excessive exercise)
  • Some investigations include:

Differential Diagnoses: Genetic Disorders

Down’s syndrome

  • Hypotonia
  • Head and face:
    • Brachycephaly and flat occiput
    • Oblique and up-slanting palpebral fissures, epicanthic folds
    • Brushfield’s spots – small grey/brown speckles on the iris
    • Small, low-set ears
    • Flat face and nose
  • Hands and feet:
    • Single palmar crease
    • A pronounced gap between the hallux and second toes
  • Some investigations include:
    • Karyotyping:
      • Shows trisomy 21
    • Diagnosis is usually confirmed at birth or antenatally, see Down’s Syndrome.

Turner syndrome

  • Short stature, primary amenorrhoea, broad chest and widely-spaced nipples, webbed neck
  • Cardiac abnormalities – coarctation of the aorta or bicuspid aortic valve – may produce heart murmurs
  • Delayed or absent puberty
  • Lymphoedema of the hands and feet – usually in neonates
  • Some investigations include:
    • Serum luteinising hormone (LH) and follicle-stimulating hormone (FSH):
      • Elevated due to ovarian failure – shows hypergonadotropic hypogonadism
    • Chromosomal analysis:
      • Diagnostic, shows 45 XO
    • Prenatal diagnosis is possible with Turner syndrome:
      • Ultrasound scan – initial screening test
      • Amniocentesis or chorionic villus sampling and karyotyping – diagnostic

Noonan syndrome

  • Short stature, webbed neck, hypertelorism, low-set ears, triangular face, pulmonary stenosis

Prader-Willi syndrome

  • Hypotonia during infancy, short stature, learning difficulties, hyperphagia and obesity, narrow face and almond-shaped eyes

Differential Diagnoses: Congenital Disorders

Achondroplasia

  • ‘Dwarfism’ – large skull, normal trunk length, but short arms and legs (rhizomelia)
  • Trident-like hands with short fingers (brachydactyly)
  • Marked lumbar lordosis
  • Forehead frontal bossing and a flat nasal bridge

Osteogenesis imperfecta

  • Recurrent fractures after minor trauma (excluding child maltreatment)
  • Blue sclera, otosclerosis and deafness

Foetal alcohol spectrum disorders (FASDs)

  • Alcohol ingestion during pregnancy, foetal alcohol syndrome is the severe end of FASDs:
    • Facial features – narrow eyes, thin upper lip, smooth/absent philtrum 
    • Problems with growth – intrauterine growth restriction, low birth weight, short stature
    • Neurodevelopmental problems – microcephaly, learning difficulties, behavioural problems

Intrauterine growth restriction without catch-up

  • Intrauterine growth restriction and small for gestational age at birth
  • Proportionally small stature but no other abnormalities

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