신경모세포종을 동반한 EZH2 유전자 변이가 확인된 위버증후군의 국내 첫 증례 보고
First Korean Case of Weaver Syndrome Along with Neuroblastoma and Genetic Confirmation of EZH2 Variant
서울대학교병원 진단검사의학과1, 의생명연구원2
Department of Laboratory Medicine1 and Biomedical Research Institute2, Seoul National University Hospital, Seoul, KoreaCorrespondence to:
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Lab Med Online 2023; 13(1): 48-52
Published January 1, 2023
Copyright © The Korean Society for Laboratory Medicine.
Weaver syndrome (WS; OMIM 277590), first reported in 1974, is a rare congenital disorder characterized by overgrowth, distinct facial features, and accelerated osseous maturation. According to a previous study, WS is caused by a variant in the enhancer of zeste homolog 2 (
A 7-month-old female was presented to the out-patient pediatrics clinic of Seoul National University Hospital with multiple palpable masses on her back, left side of the head, and extremities. The masses were approximately 1-3 cm in size and moved upon touch, but were reportedly not painful. The patient did not have any perinatal problems and was delivered at full-term. However, her height, head circumference, and weight were ≥97% of those expected for her age. The patient was tall in stature and exhibited macrocephaly. Physical examinations revealed doughy skin and umbilical hernia; however, camptodactyly, hoarse cry, and abnormal tone were absent. Her characteristic facial features included frontal bossing, round face, retrognathia, wide-spaced eyes, low-set ears, and cleft chin (Table 1). In the magnetic resonance imaging examination, a 7 cm mass was found on the left adrenal gland. Pathological examination of the mass revealed neuroblastoma on the left adrenal gland, and bone marrow aspiration confirmed the presence of neuroblastoma cells in the bone marrow (Fig. 1A).
Figure 1. Morphological characteristics of bone marrow aspirate and visualization of next-generation gene sequencing data of the patient. (A) Neuroblastoma cells cluster with fibrils (Wright-Giemsa stain, ×1,000). (B) Sequence visualization of enhancer of zeste homolog 2 (
EZH2) gene showing a missense variant, c.2050C>T.
As the patient was suspected of having overgrowth syndrome, she underwent next-generation sequencing-based gene panel testing, which revealed a heterozygous missense variant in NM_004456.4 (
Both somatic gain-of-function and loss-of-function mutations of
Diagnosing overgrowth syndrome is important for providing genetic counseling for cancer surveillance and prognosis . Particularly, patients with Beckwith-Wiedemann syndrome show an increased risk of Wilms’ tumor . The incidence of cancer is reportedly increased in patients with other overgrowth syndromes, and variants in genes such as DNA (cytosine-5)-methyltransferase 3A (
This is the first Korean case of genetically confirmed WS, accompanied by the rare occurrence of early onset neuroblastoma. Although
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