Prenatal Diagnosis and Reproductive Counselling in a Subsequent Pregnancy of a Couple with a Child Affected by FIG4-Related Leukoencephalopathy: A Case Report

Background

FIG4-related leukoencephalopathy is a rare autosomal recessive disorder of central and peripheral myelination caused by biallelic pathogenic variants in FIG4, the same gene responsible for Charcot-Marie-Tooth disease type 4J. Couples who are both carriers face a 25% recurrence risk in each subsequent pregnancy, and prenatal diagnosis is central to reproductive decision-making. Case Presentation: We describe a 32-year-old woman (G3P2L1) whose first child was diagnosed with FIG4-related leukoencephalopathy (compound heterozygous FIG4 variants, c.504C>G and c.1141C>T) after presenting with delayed development, and whose second pregnancy was terminated after prenatal testing showed the fetus to be homozygous for the familial variant. In her current, spontaneously conceived pregnancy, targeted testing on chorionic villus sampling showed the fetus to be heterozygous for the familial FIG4 variant— unlikely to be affected— while chromosomal microarray unexpectedly identified a de novo 6q27 duplication classified as a variant of uncertain significance. Serial growth ultrasound subsequently showed the fetus tracking on the 3rd–4th centile for estimated fetal weight with reassuring Doppler indices, and repeat amniocentesis reconfirmed the fetus was unlikely to be affected by FIG4-related leukoencephalopathy. After 26 weeks plus 1 day of pregnancy, the patient directly reported in labour with lower abdominal pain at 37 weeks plus 6 days. The patient delivered a female baby by LSCS in view of persistent non-reassuring NST. Weighing 2.52 kg, which was on the 16th centile, the length of the baby was 47 cm, which was on the 28th centile, and the head circumference was 34 cm, which was on the 61st centile. No resuscitation was required. The Apgar scores at 0, 5, and 10 minutes were 7, 8, and 8, respectively. The baby underwent extended screening using the 48+6 parameter. The techniques used were fluoroenzyme immunoassay for newborn screening and tandem mass spectrometry for inborn errors of metabolism. The screening results were negative for all the listed parameters in the panel, including neonatal TSH, neonatal 17-OHP, G6PD, neonatal IRT, galactose, and biotinidase. Whole-exome sequencing of the newborn was negative for the FIG-4 mutation.