背景:原发性肥大性骨关节病(PHO),也被称为Touraine-Solente-Gole综合征,是一种罕见的,由15-羟基前列腺素脱氢酶(HPGD)或溶质载体有机阴离子转运蛋白家族成员2A1(SLCO2A1)基因的致病变异引起的多系统常染色体隐性遗传疾病。然而,在一些外显率不完全的家庭中也描述了常染色体显性传播。PHO通常从童年或青春期开始,展示数字俱乐部,骨关节病,和厚皮症.我们在男性患者中描述了该综合征的完整形式,该患者具有SLCO2A1基因的纯合变体(c.1259G>T)。
方法:一名20岁的男性被转诊到我们的小儿风湿病诊所,有五年的疼痛和肿胀的病史,膝盖,脚踝和脚,延长晨僵和缓解非甾体抗炎药。他还报告了迟发性面部痤疮和掌足底多汗症。家族史无关紧要,父母是非血亲。在临床检查中,他展示了手指和脚趾的棍棒,中度痤疮和明显的面部皮肤增厚,头皮褶皱突出。他有手,膝盖,脚踝和脚肿胀。实验室检查显示炎症标志物升高。全血细胞计数,肾功能和肝功能,骨生化正常,以及免疫学小组。平片显示软组织肿胀,颅骨骨化和皮质增厚,方骨,股骨和脚趾肢骨溶解。由于没有其他提示次要原因的临床体征,我们怀疑PHO.一项基因研究揭示了一种可能的致病变异,c.1259G>T(p。Cys420Phe),SLCO2A1基因的纯合性,从而确认诊断。患者开始口服萘普生,临床明显改善。
结论:PHO在儿童炎性关节炎的鉴别诊断中,常误诊为幼年特发性关节炎(JIA)。据我们所知,这是葡萄牙患者的第二例经遗传证实的PHO病例(第一变种c.644C>T),两者都是在我们部门制造的。
BACKGROUND: Primary Hypertrophic Osteoarthropathy (PHO), also known as Touraine-Solente-Gole Syndrome, is a rare, multisystemic autosomal recessive disorder caused by pathogenic variants in the 15-hydroxyprostaglandin dehydrogenase (HPGD) or Solute Carrier Organic Anion Transporter Family Member 2A1 (SLCO2A1) genes. However, autosomal dominant transmission has also been described in some families with incomplete penetrance. PHO usually starts in childhood or adolescence, presenting with digital clubbing, osteoarthropathy, and pachydermia. We described a complete form of the syndrome in a male patient with a homozygous variant in the SLCO2A1 gene (c.1259G > T).
METHODS: A 20-year-old male was referred to our Pediatric Rheumatology Clinic with a five-year history of painful and swollen hands, knees, ankles and feet, prolonged morning stiffness and relief with non-steroidal antiinflammatory drugs. He also reported late onset facial acne and palmoplantar hyperhidrosis. Family history was irrelevant and parents were non-consanguineous. On clinical examination, he presented clubbing of the fingers and toes, moderate acne and marked facial skin thickening with prominent scalp folds. He had hand, knee, ankles and feet swelling. Laboratory investigations showed elevated inflammatory markers. Complete blood count, renal and hepatic function, bone biochemistry were normal, as well as immunological panel. Plain radiographs revealed soft tissue swelling, periosteal ossification and cortical thickening of the skull, phalanges, femur and toe acroosteolysis. Due to the absence of other clinical signs suggesting a secondary cause, we suspected PHO. A genetic study revealed a likely pathogenic variant, c.1259G > T(p.Cys420Phe), in homozygosity in the SLCO2A1 gene, thus confirming the diagnosis. The patient started oral naproxen with significant clinical improvement.
CONCLUSIONS: PHO should be kept in the differential diagnosis of inflammatory arthritis affecting children, often misdiagnosed as Juvenile Idiopathic Arthritis (JIA). To the best of our knowledge, this is the second genetically confirmed case of PHO in a Portuguese patient (first variant c.644 C > T), both made at our department.