Hemihypertrophy - more correctly called hemihyperplasia - is congenital asymmetric overgrowth affecting one side, or part of one side, of the body. It is fundamentally a comparative clinical diagnosis: you recognise it by comparing the two halves of the body and finding that one side (a limb, several limbs, the face, or a single digit) is larger.

The name matters in the exam. Hyperplasia means an increase in the number of cells, whereas hypertrophy means an increase in cell size. Because the underlying process is excessive cell proliferation, "hemihyperplasia" is the preferred term, although "hemihypertrophy" remains in common clinical use.

For the orthopaedic surgeon there are two completely separate concerns, and the examiner is testing whether you remember both:

1. The orthopaedic problem - a structural limb-length discrepancy (and sometimes localized digit or foot enlargement) that tends to worsen as the child grows, requiring monitoring and, often, growth-modulating surgery.
2. The oncological problem - an increased risk of embryonal tumours, principally Wilms tumour (nephroblastoma) and hepatoblastoma, which mandates a tumour surveillance programme and referral to clinical genetics.

Hemihyperplasia may be isolated (no other features) or a sign of a wider overgrowth syndrome, most importantly the Beckwith-Wiedemann spectrum (driven by imprinting defects at chromosome 11p15.5) and the PIK3CA-related overgrowth spectrum (PROS).

Why one side grows more

Lateralized overgrowth almost always reflects post-zygotic (somatic) mosaicism: a growth-promoting genetic or epigenetic change arises after fertilisation in one cell, and all of its descendants form the overgrown segment. This explains why overgrowth is segmental and asymmetric rather than affecting the whole body, and why most cases are sporadic with a low recurrence risk for siblings.

The Beckwith-Wiedemann spectrum (11p15.5)

The single most important syndromic association is the Beckwith-Wiedemann spectrum (BWSp), an imprinting disorder of the 11p15.5 region. This region contains growth-regulating genes (including IGF2 and CDKN1C) controlled by two imprinting centres. Loss of methylation, gain of methylation, paternal uniparental disomy (UPD), or mutations disturb the balance towards overgrowth.

The genetics is clinically useful because the molecular subtype predicts tumour risk and type. For example, paternal uniparental disomy of chromosome 11 carries a higher risk of Wilms tumour and is associated with more severe lateralized overgrowth, whereas isolated loss of methylation at one centre carries different (often lower) risk.

The PIK3CA-related overgrowth spectrum (PROS)

The other major group is PROS, caused by somatic activating mutations in PIK3CA, which switches on the PI3K-AKT-mTOR growth pathway in the affected tissue. PROS includes overlapping entities such as CLOVES syndrome, fibroadipose hyperplasia and isolated macrodactyly, and produces segmental overgrowth often combined with vascular and lipomatous lesions. Recognising PROS matters because it opens the door to targeted PI3K-pathway inhibition for severe, diffuse disease not amenable to surgery.

Histology

Biopsy of the overgrown tissue shows an increase in the number of otherwise normal cells (true hyperplasia) rather than abnormal or atypical cells - distinguishing constitutional overgrowth from a localized tumour, even though the overall predisposition to embryonal tumours is increased.

How it presents

Most children present in infancy or early childhood when a parent or clinician notices that one limb, or one side, is bigger than the other. The orthopaedic referral is often triggered by a noticeable limb-length discrepancy, a limp, or pelvic obliquity. Some are detected as part of a Beckwith-Wiedemann work-up after neonatal features such as macroglossia, an abdominal wall defect or hypoglycaemia.

Examination - compare the two sides

Because hemihyperplasia is a comparative diagnosis, examination is a systematic side-to-side comparison:

Document the pattern: which segments are enlarged (whole limb, part of a limb, single digit, face) and whether it is ipsilateral or crossed.

Measure the limbs: true and apparent leg lengths, and the block test for functional discrepancy and resulting pelvic obliquity and compensatory scoliosis.

Measure circumference and digit size: girth and digit length/width with calipers, compared with the normal side and recorded for serial monitoring.

Look for syndromic clues: macroglossia, abdominal wall scar/defect, ear creases or pits (Beckwith-Wiedemann); capillary or lipomatous/vascular lesions and macrodactyly (PROS); a port-wine stain with varicosities (Klippel-Trenaunay).

Examine the abdomen: for an organomegaly or mass (a clinical adjunct to imaging surveillance - never a substitute for it).

What examiners want you to say first

In a clinical or viva setting the marks are for recognising that this is lateralized overgrowth that needs (1) a tumour-surveillance programme and (2) a genetics referral, and only then describing how you will measure and follow the limb-length discrepancy.

Imaging the limb-length discrepancy

The orthopaedic work-up is the standard limb-length discrepancy pathway:

• Standing long-leg (scanogram / EOS) radiographs to quantify the discrepancy and identify the segment(s) involved.
• Left-hand and wrist radiograph for bone age - essential, because growth prediction and the timing of epiphysiodesis depend on skeletal rather than chronological age.
• Serial measurement over time - a single value is not enough; the trajectory drives decisions.

Tumour surveillance imaging (the non-negotiable part)

Every child with hemihyperplasia, whether isolated or syndromic, needs an embryonal-tumour surveillance programme:

• Abdominal (renal and hepatic) ultrasound every 3 months from diagnosis to about age 7-8 years - the window in which most Wilms tumours and hepatoblastomas occur.
• Serum alpha-fetoprotein (AFP) is used in some protocols (chiefly Beckwith-Wiedemann spectrum) to help detect hepatoblastoma, with the important caveat that AFP is physiologically high and variable in infancy, making interpretation difficult.

Genetic and multidisciplinary work-up

• Referral to clinical genetics for molecular testing - 11p15.5 methylation/UPD studies for Beckwith-Wiedemann spectrum, and (on overgrown tissue, not blood) PIK3CA testing where PROS is suspected, since mosaic mutations may be undetectable in blood.
• MRI of an enlarged segment when planning surgery on a digit or limb, or when a vascular/lipomatous lesion is suspected.

From the condition and its surveillance

Embryonal tumour (the key one): Wilms tumour and hepatoblastoma; the rationale for the entire surveillance programme. A late tumour can still occur after the screening window closes.

Progressive limb-length discrepancy: untreated, leads to a limp, pelvic obliquity, compensatory scoliosis and gait inefficiency.

Psychosocial impact: visible asymmetry and (for facial or digit involvement) appearance-related distress.

From treatment

Epiphysiodesis errors: overcorrection or undercorrection from mistimed surgery, angular deformity if a physis is partially arrested, and the irreversibility of the procedure.

Lengthening complications: pin-site infection, joint stiffness, premature consolidation, neurovascular injury and refracture - the reason lengthening is reserved for larger discrepancies.

Surveillance burden / false alarms: anxiety, repeated imaging, and difficult-to-interpret alpha-fetoprotein values in infancy.

The evidence underpinning hemihyperplasia care is drawn from clinical-genetics consensus work and paediatric orthopaedic cohorts (full citations are in the EvidenceCards above).

• Beckwith-Wiedemann spectrum consensus (Brioude et al, Nat Rev Endocrinol 2018) defines lateralized overgrowth as a core feature and links molecular subtype to tumour risk and surveillance - the framework for the genetics referral.
• Limb-length discrepancy evolution (Carli/De Pellegrin/Mussa et al, J Pediatr 2021) is the key orthopaedic study: discrepancy worsens with growth, the first measurement predicts the final discrepancy, and syndromic (especially paternal chromosome 11 uniparental disomy) cases are most severe.
• Tumour surveillance rationale and real-world yield (Tan & Amor, J Paediatr Child Health 2006; Zarate et al, Am J Med Genet A 2009) justify the 3-monthly abdominal ultrasound programme and show that ultrasound detects early renal/hepatic pathology while alpha-fetoprotein is hard to interpret in infancy.
• A late Wilms tumour after normal screening (Fischer/Kalish et al, Urology 2021) is a cautionary reminder that surveillance reduces but does not abolish risk.
• Timing of growth modulation (Lee et al, Bone Joint J 2013) shows the Green-Anderson growth-remaining method is the most accurate for planning epiphysiodesis, that prediction is imperfect, and that all methods tend to overcorrect.

Overall the evidence is level IV-V (consensus statements, retrospective cohorts and case reports); there are no randomised trials, reflecting the rarity of the condition.

Hemihyperplasia is too rare for arthroplasty/implant registries, and there is no single global orthopaedic guideline. Practice is shaped by clinical-genetics consensus statements (which define tumour surveillance) and by standard paediatric limb-length-discrepancy principles for the orthopaedic component.

Global epidemiology

• A recognised but rare cause of paediatric limb-length discrepancy; most cases are sporadic and reflect somatic mosaicism.
• Reported embryonal-tumour risk with isolated hemihyperplasia is in the order of a few percent (Wilms tumour quoted around 5% in some series), higher in certain Beckwith-Wiedemann molecular subgroups.
• Limb-length discrepancy increases with growth and is more severe in Beckwith-Wiedemann spectrum (especially paternal chromosome 11 uniparental disomy) than in isolated overgrowth.

Side-by-side practice positions

High- versus limited-resource practice

• High-resource settings: multidisciplinary overgrowth clinics with molecular testing, scheduled ultrasound surveillance, bone-age-based growth prediction (EOS/scanogram), and access to PI3K-inhibitor pathways for selected PROS cases.
• Limited-resource settings: diagnosis remains clinical and radiographic; the priority is to still implement abdominal ultrasound tumour surveillance (the highest-value, low-cost intervention) and to manage the discrepancy with serial clinical measurement, shoe raises and timed epiphysiodesis, which do not require advanced technology.

Lifelong-into-adolescence orthopaedic follow-up and a clear transition to adult services are important everywhere, alongside ensuring the family understands when tumour surveillance ends and that new abdominal symptoms always warrant review.