Tags

Type your tag names separated by a space and hit enter

Neu-Laxova syndrome presenting prenatally with increased nuchal translucency and cystic hygroma: The utility of exome sequencing in deciphering the diagnosis.
Am J Med Genet A. 2019 05; 179(5):813-816.AJ

Abstract

Neu-Laxova syndrome (NLS) is a lethal autosomal recessive microcephaly syndrome associated with intrauterine growth restriction (IUGR) and multiple congenital anomalies. Clinical features include central nervous system malformations, joint contractures, ichthyosis, edema, and dysmorphic facial features. Biallelic pathogenic variants in either the PHGDH or PSAT1 genes have been shown to cause NLS. Using exome sequencing, we aimed to identify the underlying genetic diagnosis in three fetuses (from one family) with prenatal skin edema, severe IUGR, micrognathia, renal anomalies, and arthrogryposis and identified a homozygous c.1A>C (p.Met1?, NM_006623.3) variant in the PHGDH gene. Loss of the translation start codon is a novel genetic mechanism for the development of NLS. Prenatal diagnosis of NLS is challenging and few reports describe the fetal pathology. Fetal neuropathologic examination revealed: delayed brain development, congenital agenesis of the corticospinal tracts, and hypoplasia of the hippocampus, cerebellum and brainstem. Each pregnancy also showed increased nuchal translucency (NT) or cystic hygroma. While NLS is rare, it may be a cause of recurrent increased NT/cystic hygroma. This finding provides further support that cystic hygroma has many different genetic causes and that exome sequencing may shed light on the underlying genetic diagnoses in this group of prenatal patients.

Authors+Show Affiliations

Regional Genetics Program, CHEO, University of Ottawa, Ottawa, Ontario, Canada.Regional Genetics Program, CHEO, University of Ottawa, Ottawa, Ontario, Canada.CHEO Research Institute, University of Ottawa, Ottawa, Ontario, Canada.Department of Human Genetics, McGill University, Montreal, Québec, Canada. McGill University and Genome Quebec Innovation Centre, Montreal, Québec, Canada.Department of Pathology and Laboratory Medicine, CHEO, University of Ottawa, Ottawa, Ontario, Canada.Department of Pathology and Laboratory Medicine, CHEO, University of Ottawa, Ottawa, Ontario, Canada.CHEO Research Institute, University of Ottawa, Ottawa, Ontario, Canada.Regional Genetics Program, CHEO, University of Ottawa, Ottawa, Ontario, Canada. CHEO Research Institute, University of Ottawa, Ottawa, Ontario, Canada.

Pub Type(s)

Case Reports
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30838783

Citation

Bourque, Danielle K., et al. "Neu-Laxova Syndrome Presenting Prenatally With Increased Nuchal Translucency and Cystic Hygroma: the Utility of Exome Sequencing in Deciphering the Diagnosis." American Journal of Medical Genetics. Part A, vol. 179, no. 5, 2019, pp. 813-816.
Bourque DK, Cloutier M, Kernohan KD, et al. Neu-Laxova syndrome presenting prenatally with increased nuchal translucency and cystic hygroma: The utility of exome sequencing in deciphering the diagnosis. Am J Med Genet A. 2019;179(5):813-816.
Bourque, D. K., Cloutier, M., Kernohan, K. D., Bareke, E., Grynspan, D., Michaud, J., & Boycott, K. M. (2019). Neu-Laxova syndrome presenting prenatally with increased nuchal translucency and cystic hygroma: The utility of exome sequencing in deciphering the diagnosis. American Journal of Medical Genetics. Part A, 179(5), 813-816. https://doi.org/10.1002/ajmg.a.61076
Bourque DK, et al. Neu-Laxova Syndrome Presenting Prenatally With Increased Nuchal Translucency and Cystic Hygroma: the Utility of Exome Sequencing in Deciphering the Diagnosis. Am J Med Genet A. 2019;179(5):813-816. PubMed PMID: 30838783.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neu-Laxova syndrome presenting prenatally with increased nuchal translucency and cystic hygroma: The utility of exome sequencing in deciphering the diagnosis. AU - Bourque,Danielle K, AU - Cloutier,Mireille, AU - Kernohan,Kristin D, AU - Bareke,Eric, AU - Grynspan,David, AU - Michaud,Jean, AU - ,, AU - Boycott,Kym M, Y1 - 2019/03/05/ PY - 2018/10/13/received PY - 2018/12/18/revised PY - 2018/12/21/accepted PY - 2019/3/7/pubmed PY - 2020/4/22/medline PY - 2019/3/7/entrez KW - PHGDH KW - Neu-Laxova syndrome KW - cystic hygroma KW - exome sequencing KW - nuchal translucency SP - 813 EP - 816 JF - American journal of medical genetics. Part A JO - Am J Med Genet A VL - 179 IS - 5 N2 - Neu-Laxova syndrome (NLS) is a lethal autosomal recessive microcephaly syndrome associated with intrauterine growth restriction (IUGR) and multiple congenital anomalies. Clinical features include central nervous system malformations, joint contractures, ichthyosis, edema, and dysmorphic facial features. Biallelic pathogenic variants in either the PHGDH or PSAT1 genes have been shown to cause NLS. Using exome sequencing, we aimed to identify the underlying genetic diagnosis in three fetuses (from one family) with prenatal skin edema, severe IUGR, micrognathia, renal anomalies, and arthrogryposis and identified a homozygous c.1A>C (p.Met1?, NM_006623.3) variant in the PHGDH gene. Loss of the translation start codon is a novel genetic mechanism for the development of NLS. Prenatal diagnosis of NLS is challenging and few reports describe the fetal pathology. Fetal neuropathologic examination revealed: delayed brain development, congenital agenesis of the corticospinal tracts, and hypoplasia of the hippocampus, cerebellum and brainstem. Each pregnancy also showed increased nuchal translucency (NT) or cystic hygroma. While NLS is rare, it may be a cause of recurrent increased NT/cystic hygroma. This finding provides further support that cystic hygroma has many different genetic causes and that exome sequencing may shed light on the underlying genetic diagnoses in this group of prenatal patients. SN - 1552-4833 UR - https://www.unboundmedicine.com/medline/citation/30838783/Neu_Laxova_syndrome_presenting_prenatally_with_increased_nuchal_translucency_and_cystic_hygroma:_The_utility_of_exome_sequencing_in_deciphering_the_diagnosis_ L2 - https://doi.org/10.1002/ajmg.a.61076 DB - PRIME DP - Unbound Medicine ER -