Putting It All Together: Postmortem Diagnosis of a Rare Ichthyosis Syndrome

Neu-Laxova syndrome (NLS) is a rare lethal disorder with autosomal recessive inheritance and is characterized by multiple congenital anomalies. Our case of NLS presented with severe intrauterine growth restriction (IUGR), abnormal facial features, severe central nervous system malformations, skeletal muscle contractures, and the hallmark signs of NLS: ichthyotic skin and excessive subcutaneous tissue with edema. Additionally, testing amniotic fluid from a prior pregnancy with a fetus showing similar abnormalities revealed several regions of homozygosity; one of these regions involved chromosome 1p13.2-p11.2, where the PHGDH gene is located. Based on the pattern of findings on serial fetal ultrasounds, postmortem neonatal exams, gross and microscopic exams, radiographs, and genetic analysis in conjunction with the clinical history and the prior pregnancy with the above-described molecular alteration, a final diagnosis of NLS was made. This rare developmental disorder is characterized by heterogenous neuroectodermal defects. Fetal ultrasound in the second trimester can help diagnose it. It is postulated to be caused by loss-of -function mutations in the PHGDH (phosphoglycerate dehydrogenase), PSAT1 (phosphoserine aminotransferase 1), and PSPH (phosphoserine phosphatase) genes, which are responsible for de novo L-serine synthesis.

Automated summary

Neu-Laxova syndrome (NLS) is a rare lethal disorder characterized by multiple congenital anomalies and autosomal recessive inheritance. A case of NLS exhibited severe intrauterine growth restriction, abnormal facial features, central nervous system malformations, skeletal muscle contractures, ichthyotic skin, excessive subcutaneous tissue with edema, and homozygosity in chromosome 1p13.2-p11.2. Based on multiple tests and genetic analysis, NLS was diagnosed. NLS is a rare developmental disorder with heterogenous neuroectodermal defects caused by loss-of-function mutations in PHGDH, PSAT1, and PSPH genes responsible for de novo L-serine synthesis.