Novel ZBTB20 variant in a patient with Primrose syndrome

Primrose syndrome is a rare autosomal dominant syndrome caused by heterozygous variants in ZBTB20. Clinical characteristics include intellectual disability, macrocephaly, ocular abnormalities, hearing loss, calcification of the external ear cartilage, nonspecific brain magnetic resonance imaging (MRI) findings, cryptorchidism, contractures, distal muscle wasting, sparse body hair, cataract, disturbed glucose metabolism, anemia, and osteoporosis. The clinical manifestations are variable and age-dependent. Fewer than 60 patients with Primrose syndrome have been reported to date. Until recently, the majority of affected individuals had been adults because the phenotype becomes more recognizable over time.
We report on a 3-year-old girl with developmental delay and macrocephaly. Facial dysmorphic features included ptosis, deep-set eyes and small ear lobes. Brain MRI revealed dysgenesis of the corpus callosum. Family history was unremarkable. Trio-exome analysis identified a novel heterozygous de novo missense variant in ZBTB20 [c.1805G>A, p.(Gly602Asp)].
The patient reported here corroborates previous clinical observations and expands the mutational spectrum of Primrose syndrome. This case also illustrates the usefulness of exome sequencing in diagnosing syndromes that are difficult to recognize in young patients.

普里姆罗斯综合征（Primrose syndrome）是一种罕见的常染色体显性综合征，由ZBTB20基因的杂合变异引发。其临床特征包括智力障碍、巨头畸形、眼部异常、听力损失、外耳软骨钙化、非特异性颅脑磁共振成像（MRI）表现、隐睾症、挛缩、远端肌肉萎缩、体毛稀疏、白内障、糖代谢紊乱、贫血及骨质疏松症。该病临床表现具有变异性且呈年龄依赖性。截至目前，全球已报道的普里姆罗斯综合征患者不足60例；此前多数确诊患者为成年人，这是由于该综合征的表型随病程延长更易被识别。
本次研究报道1例表现为发育迟缓与巨头畸形的3岁女童。该患儿的面部畸形特征包括上睑下垂、眼窝深陷及小耳垂。颅脑MRI检查显示胼胝体发育不良。家族史无异常。三人外显子组测序分析检出ZBTB20基因1个新发杂合错义变异[c.1805G>A，p.(Gly602Asp)]。
本次报道的病例佐证了此前的临床观察结果，拓展了普里姆罗斯综合征的突变谱。该病例同时证明了外显子组测序在诊断年幼患者难以识别的综合征时具有重要应用价值。