Primrose syndrome (PS; MIM# 259050) is characterized by intellectual disability (ID), macrocephaly, unusual facial features (frontal bossing, deeply set eyes, down-slanting palpebral fissures), calcified external ears, sparse body hair and distal muscle wasting. The syndrome is caused by de novo heterozygous missense variants in ZBTB20. Most of the 29 published patients are adults as characteristics appear more recognizable with age. We present 13 hitherto unpublished individuals and summarize the clinical and molecular findings in all 42 patients. Several signs and symptoms of PS develop during childhood, but the cardinal features, such as calcification of the external ears, cystic bone lesions, muscle wasting, and contractures typically develop between 10 and 16 years of age. Biochemically, anemia and increased alpha-fetoprotein levels are often present. Two adult males with PS developed a testicular tumor. Although PS should be regarded as a progressive entity, there are no indications that cognition becomes more impaired with age. No obvious genotype-phenotype correlation is present. A subgroup of patients with ZBTB20 variants may be associated with mild, nonspecific ID. Metabolic investigations suggest a disturbed mitochondrial fatty acid oxidation. We suggest a regular surveillance in all adult males with PS until it is clear whether or not there is a truly elevated risk of testicular cancer.

中文翻译：

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报春花综合症：42位患者的表型特征。

报春花综合症（PS; MIM＃259050）的特征是智力残疾（ID），大头畸形，不寻常的面部特征（额叶凸起，眼睛深陷，睑裂向下倾斜），外耳钙化，体毛稀疏和远端肌肉消瘦。该综合征是由ZBTB20中的从头杂合错义变异引起的。在公布的29位患者中，大多数都是成年人，因为随着年龄的增长，特征会越来越明显。我们介绍了13个迄今未发表的个体，并总结了全部42例患者的临床和分子发现。儿童期会出现PS的几种体征和症状，但基本特征（例如外耳钙化，囊性骨病变，肌肉消瘦和挛缩）通常会在10至16岁之间发展。生化方面 经常出现贫血和甲胎蛋白水平升高。两名患有PS的成年男性患了睾丸肿瘤。尽管PS应该被认为是一个进步的个体，但没有迹象表明认知随着年龄的增长而变得越来越弱。没有明显的基因型-表型相关性存在。ZBTB20变异患者的亚组可能与轻度非特异性ID相关。代谢研究表明线粒体脂肪酸氧化受到干扰。我们建议对所有患有PS的成年男性进行定期检查，直到明确是否确实存在睾丸癌的真正风险增加为止。没有明显的基因型-表型相关性存在。ZBTB20变异患者的亚组可能与轻度非特异性ID相关。代谢研究表明线粒体脂肪酸氧化受到干扰。我们建议对所有患有PS的成年男性进行定期检查，直到明确是否确实存在睾丸癌的真正风险增加为止。没有明显的基因型-表型相关性存在。ZBTB20变异患者的亚组可能与轻度非特异性ID相关。代谢研究表明线粒体脂肪酸氧化受到干扰。我们建议对所有患有PS的成年男性进行定期检查，直到明确是否确实存在睾丸癌的真正风险增加为止。