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

Overview

Journal Cureus

Specialty Biomedical Engineering

Date 2023 Jun 12

PMID 37303350

Authors

Pragya Virendrakumar Jain

Jauntea Maxey

Michael W Lawlor

Lauren N Parsons

Affiliations

Soon will be listed here.

Abstract

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 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 (phosphoglycerate dehydrogenase), (phosphoserine aminotransferase 1), and (phosphoserine phosphatase) genes, which are responsible for de novo L-serine synthesis.

References

Tabatabaie L, de Koning T, Geboers A, van den Berg I, Berger R, Klomp L . Novel mutations in 3-phosphoglycerate dehydrogenase (PHGDH) are distributed throughout the protein and result in altered enzyme kinetics. Hum Mutat. 2009; 30(5):749-56. DOI: 10.1002/humu.20934. View

King J, Gardner V, Chen H, Blackburn W . Neu-Laxova syndrome: pathological evaluation of a fetus and review of the literature. Pediatr Pathol Lab Med. 1995; 15(1):57-79. DOI: 10.3109/15513819509026940. View

Kaur A, Suranagi V, Patil K, Bannur H . Neu-Laxova Syndrome: An Unusual Association with Kyphosis. Turk Patoloji Derg. 2017; 34(3):259-261. DOI: 10.5146/tjpath.2015.01353. View

Acuna-Hidalgo R, Schanze D, Kariminejad A, Nordgren A, Kariminejad M, Conner P . Neu-Laxova syndrome is a heterogeneous metabolic disorder caused by defects in enzymes of the L-serine biosynthesis pathway. Am J Hum Genet. 2014; 95(3):285-93. PMC: 4157144. DOI: 10.1016/j.ajhg.2014.07.012. View

Winter R, Donnai D, CRAWFURD M . Syndromes of microcephaly, microphthalmia, cataracts, and joint contractures. J Med Genet. 1981; 18(2):129-33. PMC: 1048685. DOI: 10.1136/jmg.18.2.129. View

Shved I, Lazjuk G, Cherstvoy E . Elaboration of the phenotypic changes of the upper limbs in the Neu-Laxova syndrome. Am J Med Genet. 1985; 20(1):1-11. DOI: 10.1002/ajmg.1320200102. View

Shaheen R, Rahbeeni Z, Alhashem A, Faqeih E, Zhao Q, Xiong Y . Neu-Laxova syndrome, an inborn error of serine metabolism, is caused by mutations in PHGDH. Am J Hum Genet. 2014; 94(6):898-904. PMC: 4121479. DOI: 10.1016/j.ajhg.2014.04.015. View

de Koning T, Klomp L, van Oppen A, Beemer F, Dorland L, van den Berg I . Prenatal and early postnatal treatment in 3-phosphoglycerate-dehydrogenase deficiency. Lancet. 2004; 364(9452):2221-2. DOI: 10.1016/S0140-6736(04)17596-X. View

Kainer F, PRECHTL H, Dudenhausen J, Unger M . Qualitative analysis of fetal movement patterns in the Neu-Laxova syndrome. Prenat Diagn. 1996; 16(7):667-9. DOI: 10.1002/(SICI)1097-0223(199607)16:7<667::AID-PD926>3.0.CO;2-B. View

10.

Manning M, Cunniff C, Colby C, El-Sayed Y, Hoyme H . Neu-Laxova syndrome: detailed prenatal diagnostic and post-mortem findings and literature review. Am J Med Genet A. 2004; 125A(3):240-9. DOI: 10.1002/ajmg.a.20467. View

11.

Khajavi H, Gharavi M . Neu-Laxova syndrome: report of a case and comments. Am J Med Genet. 1987; 28(1):17-23. DOI: 10.1002/ajmg.1320280104. View

12.

Russo R, DArmiento M, Martinelli P, VENTRUTO V . Neu-Laxova syndrome: pathological, radiological, and prenatal findings in a stillborn female. Am J Med Genet. 1989; 32(1):136-9. DOI: 10.1002/ajmg.1320320129. View

13.

Klomp L, de Koning T, Malingre H, van Beurden E, Brink M, Opdam F . Molecular characterization of 3-phosphoglycerate dehydrogenase deficiency--a neurometabolic disorder associated with reduced L-serine biosynthesis. Am J Hum Genet. 2000; 67(6):1389-99. PMC: 1287916. DOI: 10.1086/316886. View

14.

Fitch N, Resch L, Rochon L . The Neu-Laxova syndrome: comments on syndrome identification. Am J Med Genet. 1982; 13(4):445-52. DOI: 10.1002/ajmg.1320130415. View

15.

Tarim E, Bolat F . Prenatal diagnosis and postmortem findings of Neu-laxova syndrome. J Turk Ger Gynecol Assoc. 2014; 11(4):225-7. PMC: 3939158. DOI: 10.5152/jtgga.2010.44. View

16.

Rode M, Mennuti M, Giardine R, Zackai E, Driscoll D . Early ultrasound diagnosis of Neu-Laxova syndrome. Prenat Diagn. 2001; 21(7):575-80. DOI: 10.1002/pd.101. View

17.

Coto-Puckett W, Gilbert-Barness E, Steelman C, Stuart T, Robinson H, Shehata B . A spectrum of phenotypical expression OF Neu-Laxova syndrome: Three case reports and a review of the literature. Fetal Pediatr Pathol. 2010; 29(2):108-19. DOI: 10.3109/15513811003620914. View