家系基因谱不典型的假性甲状旁腺功能减退症1例并文献复习

Pseudohypoparathyroidism in a Family with Atypical Genetic Profile:a Case Report and Literature Review

目的报道1例家系基因谱不典型的假性甲状旁腺功能减退症(PHP),分享此癫痫为首发症状的罕见病的诊疗思路。方法总结先证者和家系成员的相关临床特点,并完善基因检测,同时检索PubMed、CNKI和万方数据库中相似突变位点的病例报告,分析携带该突变患儿的临床特征差异。结果先证者14岁,以癫痫为首发症状,检查示低钙、高磷、高PTH血症,伴矮小、智力低下、牙釉质发育不全合并原发性甲状腺功能减退,结合典型临床表现和测序分析结果,先证者确诊为PHP1a型。先证者同胞弟弟有部分AHO体征,但无低钙、高磷、高甲状旁腺激素表现。家系基因谱分析发现先证者携带GNAS:c.348dup(p.V117Rfs*23)杂合突变,但其弟弟和父母均无该基因突变。结论以癫痫为首发症状的PHP,早期容易被误诊,临床若发现AHO体征,应及时完善相关辅助检查,必要时进行家系基因检测,以便早诊断早治疗。

Objective To report a case of pseudohypoparathyroidism(PHP)with atypical genetic profile,and to share the diagnosis and treatment of this rare disease with epilepsy as the first symptom.Methods The clinical characteristics of the proband and family members were summarized,and the genetic testing was improved.The case reports of similar mutation were searched in PubMed,CNKI and Wanfang databases,and the clinical characteristics of children with the mutation were analyzed.Results The 14-year-old proband with epilepsy as the first symptom was found to have hypocalcemia,hyperphosphatemia,hyperparathyrotinemia,short stature,hypophrenia,enamel hypoplasia,and primary hypothyroidism.Combining typical clinical presentation and sequencing results,the proband was diagnosed as PHP type 1a.The younger brother of the proband also presented with AHO signs,but had normal calcium,phosphorus and PTH levels.Genome-wide exon sequencing revealed a heterozygous mutation in GNAS:c.348dup(p.V117Rfs*23),which was absent in his brother and parents.Conclusion PHP with epilepsy as the first symptom is easy to be misdiagnosed in the early stage.If AHO signs are found,the relevant auxiliary examinations should be improved in time.Furthermore,family gene testing should be performed if necessary for early diagnosis and treatment.