Case Report: Familial hCG syndrome with elevated hCG level concurrently in blood and cerebrospinal fluid

Objective To describe a rare pediatric case of familial human chorionic gonadotropin (hCG) syndrome presenting with concurrent elevation of beta-hCG (β-hCG) in both blood and cerebrospinal fluid (CSF). This report aims to expand the phenotypic spectrum of this condition and discuss diagnostic challenges to avoid misdiagnosing this benign disorder as an intracranial malignancy. Methods Clinical data were collected from the proband, an 8-year-9-month-old girl presenting with central precocious puberty (CPP) and unexplained hCG elevation. To evaluate the differential recognition of hCG variants by diverse detection antibodies, serum and CSF β-hCG levels were cross-monitored using both Abbott Architect and Roche Elecsys platforms. Additional evaluations included magnetic resonance imaging (MRI), computed tomography (CT), and pathological examination. Whole-exome sequencing (WES) and family screening of first-degree relatives were conducted to identify the etiology. A literature review regarding familial hCG syndrome was also conducted. Results The patient was initially diagnosed with CPP due to breast development and accelerated growth. During routine screening to exclude tumor-associated precocious puberty, she was found to have elevated serum β-hCG (132.1–136.3 IU/L, Roche Elecsys) and was referred to our hospital. Imaging revealed a pineal cyst without evidence of tumor. Both serum and CSF β-hCG levels were elevated (45.58 and 103.22 IU/L, respectively; Abbott Architect), with CSF levels exceeding serum. Despite chemotherapy, radiotherapy, and pineal cyst resection (histology: central neurocytoma), hCG remained persistently elevated. Given the benign clinical course and lack of therapeutic response, segregation analysis was subsequently performed. Elevated serum β-hCG levels were identified in the patient’s asymptomatic mother and prepubertal younger brother (43.79 and 64.58 mIU/mL, respectively; Abbott). Whole-exome sequencing was negative. Familial hCG syndrome was finally diagnosed, and it was determined that her CPP was an independent, concurrent condition. Oncological treatments were ceased, and the girl continued gonadotropin-releasing hormone agonist (GnRHa) treatment. Conclusion This case report describes a novel clinical finding in familial hCG syndrome characterized by concurrent elevation of β-hCG in both serum and CSF. This finding significantly expands the phenotypic spectrum of this benign condition.