Neu-Laxova syndrome presenting prenatally with increased nuchal translucency and cystic hygroma: The utility of exome sequencing in deciphering the diagnosis.

Bourque, Danielle K; Cloutier, Mireille; Kernohan, Kristin D; Bareke, Eric; Grynspan, David; Michaud, Jean; Boycott, Kym M

Bourque, Danielle K; Cloutier, Mireille; Kernohan, Kristin D; Bareke, Eric; Grynspan, David; Michaud, Jean; Boycott, Kym M.

Afiliación

Bourque DK; Regional Genetics Program, CHEO, University of Ottawa, Ottawa, Ontario, Canada.
Cloutier M; Regional Genetics Program, CHEO, University of Ottawa, Ottawa, Ontario, Canada.
Kernohan KD; CHEO Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
Bareke E; Department of Human Genetics, McGill University, Montreal, Québec, Canada.
Grynspan D; McGill University and Genome Quebec Innovation Centre, Montreal, Québec, Canada.
Michaud J; Department of Pathology and Laboratory Medicine, CHEO, University of Ottawa, Ottawa, Ontario, Canada.
Boycott KM; CHEO Research Institute, University of Ottawa, Ottawa, Ontario, Canada.

Am J Med Genet A ; 179(5): 813-816, 2019 05.

Article en En | MEDLINE | ID: mdl-30838783

RESUMEN

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.

Asunto(s)

Anomalías Múltiples/diagnóstico; Anomalías Múltiples/genética; Encefalopatías/diagnóstico; Encefalopatías/genética; Retardo del Crecimiento Fetal/diagnóstico; Retardo del Crecimiento Fetal/genética; Estudios de Asociación Genética; Predisposición Genética a la Enfermedad; Ictiosis/diagnóstico; Ictiosis/genética; Deformidades Congénitas de las Extremidades/diagnóstico; Deformidades Congénitas de las Extremidades/genética; Linfangioma Quístico/diagnóstico; Linfangioma Quístico/genética; Microcefalia/diagnóstico; Microcefalia/genética; Medida de Translucencia Nucal; Autopsia; Biopsia; Estudios de Asociación Genética/métodos; Humanos; Análisis de Secuencia de ADN; Secuenciación del Exoma

Palabras clave

PHGDH; Neu-Laxova syndrome; cystic hygroma; exome sequencing; nuchal translucency

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Anomalías Múltiples / Encefalopatías / Linfangioma Quístico / Deformidades Congénitas de las Extremidades / Predisposición Genética a la Enfermedad / Medida de Translucencia Nucal / Estudios de Asociación Genética / Retardo del Crecimiento Fetal / Ictiosis / Microcefalia Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Humans Idioma: En Revista: Am J Med Genet A Asunto de la revista: GENETICA MEDICA Año: 2019 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos

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