Abstract / Summary
Abstract Objective To report a prenatal diagnosis case of pontocerebellar hypoplasia type 16 (PCH16) caused by novel MINPP1 gene variants, analyze its imaging features and novel gene mutation sites, so as to provide reference for prenatal diagnosis and genetic counseling of PCH. Method Clinical follow-up was performed on a pregnant woman with abnormal findings on routine prenatal ultrasonography at 31 gestational weeks. Ultrasonography revealed fetal head circumference below the 1st percentile, markedly reduced transverse cerebellar diameter (TCD) below the 1st percentile, accompanied by abnormal thalamic morphology. Fetal cranial magnetic resonance imaging (MRI) and whole exome sequencing (WES) of the fetus and its parents were further conducted. Meanwhile, we compared our results with the existing literature. Results Both prenatal ultrasound and fetal cranial MRI highly indicated fetal cerebellar hypoplasia. WES demonstrated that the fetus carried two novel compound heterozygous variants in the MINPP1 gene: c.1460T > G (p.Leu487Arg) and c.430G > A (p.Gly144Arg). Combined with imaging manifestations and genetic testing results, the fetus was provisionally diagnosed with PCH16. Up to the present report, all previously published PCH16 cases were diagnosed postnatally. This case is the first globally reported prenatally diagnosed PCH16 fetus. Conclusion Routine measurement of fetal TCD in the third trimester is conducive to early screening of suspected PCH cases. PCH16 should be highly suspected when abnormal thalamic morphology is simultaneously present. Combined fetal cranial MRI can further clarify intracranial structural malformations. Timely WES for fetuses with abnormal prenatal imaging findings contributes to etiological diagnosis, and provides reliable clinical evidence for fetal prognosis assessment, familial genetic counseling and prenatal intervention in subsequent pregnancies. Clinical trial number Not applicable.