Familial Isolated Hemihyperplasia Recurrence in a Non-Consecutive Brother and Sister Punctuated by Unaffected Children: A Case Series with 10-Year Follow-Up and Review of Clinical Diagnostic Thresholds

Abstract

Isolated hemihyperplasia (IH) is a rare congenital overgrowth disorder defined as regional body asymmetry involving bone, soft tissue, or both, without syndromic features. While predominantly sporadic with a postzygotic somatic aetiology, non-consecutive familial clustering within a single sibship is exceptionally rare and challenges conventional genetic paradigms. We report a unique familial case series of isolated hemihyperplasia affecting two non-consecutive siblings born to healthy, non-consanguineous Libyan parents with a negative family history. The pedigree includes five children, where the third child (Case 2, a 10-year-old female) and the fifth child (Case 1, a 1-year-old male) are affected, separated by healthy children. Case 1 presented at 12 months with left-sided lower limb hypertrophy exhibiting a 2 cm length discrepancy and a 13% thigh circumference mismatch (Left: 26 cm, Right: 23 cm), satisfying the >5% clinical diagnostic threshold. Case 2 initially presented at 7 months with right-sided lower limb hypertrophy. Over a 10-year longitudinal follow-up, she maintained a benign clinical course; serial abdominal ultrasonographies every 3–4 months and normal serum alpha-fetoprotein (AFP) profiles successfully ruled out embryonal malignancies. Her persistent 2.5 cm limb-length discrepancy and acral overgrowth were stably managed via a conservative custom shoe lift. Key pathognomonic markers of Beckwith-Wiedemann syndrome were consistently absent in both siblings. The recurrence of isolated hemihyperplasia in non-consecutive siblings suggests an underlying heritable germline susceptibility or parental mosaicism with incomplete penetrance. This series provides crucial 10-year prognostic data demonstrating that oncological risks diminish substantially toward late childhood. It underscores the clinical necessity of strict long-term tumour surveillance and early interdisciplinary orthopaedic management for active limb discrepancies.