Differentiating asymmetrical overgrowth syndromes: a case study.

Abstract

Background: Asymmetrical overgrowth has many genetic causes with significant clinical overlap, including CLOVES syndrome, Proteus syndrome (PS), Beckwith-Wiedemann syndrome (BWS), PTEN-hamartoma syndrome (PHS), neurofibromatosis type 1 syndrome, hemihyperplasia-multiple lipomatous syndrome (HHML) and isolated macrodactyly (IM), often resulting in misdiagnosis. CLOVES syndrome is characterized by congenital lipomatous overgrowth, vascular malformations, epidermal nevi and scoliosis, and with HHML, forms part of the PIK3CA-related overgrowth spectrum (PROS). This case study aims to promote the consideration and correct diagnosis of this rare group of disorders. Case report: We describe a 26-month-old girl with focal overgrowth and lipomatous lesions of her left lower extremity, with epidermal pigmentation. She had a benign renal cyst, and normal intelligence and neurodevelopment. The overgrowth has not been progressive.While genetic testing was unavailable, her symptoms place her between CLOVES syndrome and HHML in the PIK3CA spectrum. Discussion(s): Some identifying features can help clinicians diagnose overgrowth syndromes. One feature is the natural history. Most present prenatally with proportionate progression, whereas PS presents with postnatal onset and aggressive progression. Classic signs like splaying of the feet in CLOVES syndrome, cerebriform connective tissue nevi in PS, and incidence of specific cancers in BWS and PHS also facilitate differentiation. In cases such as ours, when genetic confirmation is not easily accessible, the clinical picture can often provide clues for the discerning clinician. It is now recognized that CLOVES syndrome, HHML, megalencephaly syndromes, fibroadipose overgrowth and IM are all due to PIK3CA mutations and form the clinical continuum of PROS.