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. 2022 Sep 30;15(1):206.
doi: 10.1186/s12920-022-01362-1.

Clinical and genetic analyses of patients with lateralized overgrowth

Yoon-Myung Kim  1 , Yena Lee  2 , Yunha Choi  2 , In Hee Choi  2 , Sun Hee Heo  3 , Jung Min Choi  3 , Hyo-Sang Do  3 , Ja-Hyun Jang  4 , Mi-Sun Yum  2 , Han-Wook Yoo  2   5 , Beom Hee Lee  6   7
Affiliations

Clinical and genetic analyses of patients with lateralized overgrowth

Yoon-Myung Kim et al. BMC Med Genomics. .

Abstract

Background: The genetic features and treatment strategies of lateralized overgrowth have been elusive. We performed this study to analyze the genetic characteristics and treatment results of propranolol- or alpelisib-treated patients with lateralized overgrowth.

Methods: Fifteen patients with lateralized overgrowth were involved. Clinical characteristics and whole-body magnetic resonance imaging (WB-MRI) findings were evaluated. Targeted exome sequencing with a gene panel of affected tissue and peripheral white blood cells was performed. Propranolol was administered and treatment results were evaluated. The PIK3CA inhibitor alpelisib was prescribed via a managed access program.

Results: The identified mutations were PIK3CA (n = 7), KRAS (n = 2), PTEN (n = 1), MAP2K3 (n = 1), GNAQ (n = 1), TBC1D4 (n = 1), and TEK (n = 1). Propranolol was prescribed in 12 patients, and 7 experienced mild improvement of symptoms. Alpelisib was prescribed in two patients with a PIK3CA mutation, and the reduction of proliferated masses after 1 year of treatment was proved by WB-MRI.

Conclusions: Targeted exome sequencing identified various genetic features of lateralized overgrowth. Propranolol could be applied as an adjuvant therapy for reducing vascular symptoms, but a PIK3CA inhibitor would be the primary therapeutic strategy for PIK3CA-related overgrowth syndrome.

Keywords: Alpelisib; Lateralized overgrowth; PIK3CA-related segmental overgrowth syndrome; Targeted exome sequencing.

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Conflict of interest statement

The authors report no disclosures relevant to the manuscript.

Figures

Fig. 1
Fig. 1
Clinical manifestations of patients. A Patient 5 with a PIK3CA mutation with prominent superficial venous engorgement. The superficial venous engorgement showed improvement after 3 years of propranolol administration. B Patient 1 with a PIK3CA mutation showing port-wine stain of the skin and hypertrophy of the right leg. C Patient 10 with a PTEN mutation presented with epidermal nevus. The color of the epidermal nevus faded after 6 months of propranolol administration. D Patient 9 with a KRAS mutation showing hypertrophy of the right leg
Fig. 2
Fig. 2
Change in the MRI findings of patient 3 after the administration of alpelisib. A The MRI image of both lower legs before treatment B The MRI image of both legs after treatment. The extent of fine stranding of the subcutaneous layer of the bilateral distal lower legs decreased. Minimal improvement of the tortuous and dilated deep and superficial venous structure in the lower extremities was observed
See this image and copyright information in PMC

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