Department of Pediatrics, Inha University Hospital, Inha University College of Medicine, Incheon, Korea.
Northwest Gyeonggi Regional Center for Rare Disease, Inha University Hospital, Incheon, Korea.
J Korean Med Sci. 2021 May 10;36(18):e133. doi: 10.3346/jkms.2021.36.e133.
Weiss-Kruszka syndrome (WSKA), caused by heterozygous loss-of-function variants in gene, is a recently described and extremely rare genetic disorder. The main phenotypes include characteristic craniofacial features, ptosis, dysgenesis of the corpus callosum, and neurodevelopmental impairment. We report the first Korean boy with molecularly confirmed WSKA presenting with an atypical manifestation. A 16-year-old boy with a history of bilateral ptosis surgery presented with short stature (-3.49 standard deviation score) and delayed puberty. The patient showed characteristic craniofacial features including an inverted triangular-shaped head, exaggerated Cupid's bow, arched eyebrows, down-slanting palpebral fissures, and poorly expressive face. He had a mild degree of intellectual disability and mild hypotonia. Endocrine studies in the patient demonstrated complete growth hormone deficiency (GHD) associated with empty sella syndrome (ESS), based on a magnetic resonance imaging study for the brain that showed a flattened pituitary gland and cerebrospinal fluid space herniated into the sella turcica. To identify the genetic cause, we performed whole exome sequencing (WES). Through WES, a novel heterozygous nonsense variant, c.4185del; p.(Met1396Ter) in was identified. This is the first case of WSKA accompanied by primary ESS associated with GHD. More clinical and functional studies are needed to elucidate this association.
韦斯-克鲁斯卡综合征（WSKA）是一种最近描述的极其罕见的遗传性疾病，由 基因的杂合功能丧失变异引起。主要表型包括特征性的颅面特征、上睑下垂、胼胝体发育不良和神经发育障碍。我们报告了首例经分子证实的伴有非典型表现的韩国男孩 WSKA。一名 16 岁的男孩有双侧上睑下垂手术史，表现为身材矮小（-3.49 标准差评分）和青春期延迟。患者表现出特征性的颅面特征，包括倒三角形头部、夸张的丘比特弓、拱形眉毛、下垂的睑裂和表情不佳。他有轻度智力残疾和轻度肌张力低下。患者的内分泌研究显示，基于大脑磁共振成像显示垂体扁平且脑脊液空间疝入蝶鞍，存在完全生长激素缺乏症（GHD）伴空泡蝶鞍综合征（ESS）。为了确定遗传原因，我们进行了全外显子组测序（WES）。通过 WES，在 中发现了一个新的杂合无义变异 c.4185del;p.(Met1396Ter)。这是首例伴有原发性 ESS 伴 GHD 的 WSKA。需要更多的临床和功能研究来阐明这种关联。
