Prenatal phenotype of PNKP-related microcephaly, seizures, and developmental delay: A case report and literature review.

Rationale: Microcephaly, epilepsy, and developmental delay (MCSZ) is a rare neurodevelopmental disorder associated with autosomal recessive inheritance of mutations in the polynucleotide kinase 3'-phosphatase (PNKP) gene. Prompt identification and management are essential, as delayed diagnosis or intervention may result in severe complications or mortality. In this case, prenatal screening in the second trimester detected fetal microcephaly with a gradual decline in head circumference, prompting the decision to terminate the pregnancy. Subsequent genetic analysis of the fetal tissue confirmed the presence of compound heterozygous mutations in the PNKP gene.

Patient Concerns: The patient, a 34-year-old remarried female with no history of consanguineous marriage, underwent 2 mid-trimester termination procedures due to fetal microcephaly and sought counseling for reproductive assistance.

Diagnoses: The patient's carrier status for PNKP mutations was ascertained through whole-exome sequencing of the termination tissue and molecular genetic testing for monogenic disorders. The terminated fetus was diagnosed with MCSZ, a condition associated with compound heterozygous mutations in the PNKP gene.

Interventions: Fetal microcephaly was identified via mid-trimester prenatal ultrasound, leading to the termination of the pregnancy during the same trimester. Subsequent genetic analysis of the immediate family revealed compound heterozygous mutations in the PNKP gene as the underlying cause of MCSZ. Genetic counseling was provided, followed by 1 cycle of preimplantation genetic testing for monogenic.

Outcomes: The patient carried the heterozygous c.1188 + 1G > A PNKP mutation, whereas her husband carried the heterozygous c.976G > A PNKP mutation. The fetus was found to have compound heterozygous mutations c.976G > A and c.1188 + 1G > A. After counseling, the couple underwent 1 cycle of preimplantation genetic testing for monogenic, unfortunately, no pregnancy occurred after the 2 embryos were transferred.

Lessons: MCSZ, a condition caused by PNKP mutations, is exceedingly rare. Women with a history of adverse pregnancy outcomes should undergo close monitoring during prenatal checkups. If fetal microcephaly is detected, it is essential to strictly follow obstetric guidelines for prenatal care, such as comprehensive cranial magnetic resonance imaging and genetic testing for confirmation. Avoidance of consanguineous marriages is advised. Early detection and timely intervention are key to preventing adverse pregnancy outcomes.