ESPE Abstracts

Background: Familial hCG syndrome is a rare and benign cause of elevated serum beta human chorionic gonadotropin (β- hCG), moreover, elevated β-hCG in cerebrospinal fluid(CSF) has never been reported in familial hCG syndrome.

Object: To report the two Chinese families of familial hCG syndrome with elevated β-hCG concurrently in blood/CSF.

Method: We described the clinical data of 2 cases of familial hCG syndrome in our department in Dec 2020 and Dec 2021, respectively，and reviewed the relative literatures.

Result: Case 1 and case 2 were apparently healthy girls (8y9m, 8y5m) born to non-consanguineous parents from two unrelated families. They were locally diagnosed as central precocious puberty (CPP) and partial CPP at the age of 8y2m and 8y3m, respectively, for early breast development and referred to our hospital both for elevated serum β-hCG level. Serum β-hCG levels(Abbott) were elevated with higher CSF β-hCG levels (Case 1: 45.58 vs 103.22mIU/mL; Case 2: 36.8 vs 139.51 mIU/mL) with normal AFP levels. Whole body positron emission tomography-computed tomography, magnetic resonance imaging of the head, chest, abdomen and pelvis revealed nothing except pineal cyst in Case 1. In case 1, intracranial non-germinomatous germ cell tumor(INGGCT) was diagnosed， and combination chemotherapy was initiated with GnRHa therapy for CPP. Because of unchangeable serum and CSF β-hCG levels after four course, she went to another brain hospital, where radiotherapy and subsequently pinealectomy (without GCT pathological characteristics) were performed without any β-hCG response either. Considering benign condition, we detected her two younger brothers and parents and found elevated β-hCG level in her mense-regular mother and one non-precocious younger brother (64.58 and 43.79 mIU/mL, respectively). Whole exon sequencing was negative. Familial hCG syndrome was finally diagnosed. With the first case experience, in case 2, we soon started to detect β-hCG in the family without initiation of chemotherapy, with the finding of elevated β-HCG in other 3(father, old sister, and grandmother) of 5 of the asymptomatic relatives (parents, sisters, grandparents) (46.13, 55.51, and 89.70 mIU/mL, respectively), with higher CSF level(146.18 mIU/mL) in the father who accepted lumbar puncture. Familial hCG syndrome was also diagnosed. Both of the two family were greatly relievedly.

Conclusion: We firstly report two rare families of familial hCG syndrome with simultaneous elevation of hCG in peripheral blood and cerebrospinal fluid， which broadens the clinical spectrum of familial hCG syndrome.