Prenatal Diagnosis of Neu–Laxova Syndrome

Abstract

Neu–Laxova syndrome is a rare and lethal genetic disease with autosomal recessive inheritance involving abnormalities of multiple systems. It was first reported in 1971. Since then, just eighty-eight cases have been reported. The syndrome is characterized by early and severe growth restriction, and craniofacial anomalies, such as microcephaly, hypertelorism and other malformations, resulting in quite characteristic features. Additionally, it might appear as generalized edema, flexion contractures and other malformations of the extremities, abnormalities in the CNS (central nervous system), skin (severe ichthyosis), and genitourinary and cardiac abnormalities. We present the case of a patient who had her first pregnancy with a fetus with Neu–Laxova syndrome diagnosed in our center during the second-trimester ultrasound. The ultrasound findings suggested the diagnosis, which was confirmed with a genetic study of the amniotic fluid: the variant of the PSAT1 gene, associated with NLS (Neu–Laxova syndrome) 2 in homozygosis. Moreover, there was a second pregnancy with a fetus carrying the same mutation in heterozygosis. In addition, we have carried out a review of published literature about this disease up to the present time.

Neu Laxova Syndrome—A Terrifying Disease in Two Siblings With a Novel Variant in PHGDH Gene

“…At least 90 cases have been described in the literature, many of them were diagnosed after birth. 9 Early and sequential US examinations are crucial and should be performed in order to establish an early diagnosis. It is important that potential new variants and new phenotypes are published in order to enrich the recognition of this disease.…”

“…Other SNC anomalies include hypoplasia of the cerebellum (36%), agenesis of the corpus callosum (36%), and those described above (lissencephaly in 45% and ventriculomegaly in 17%); other dysmorphic features include hypertelorism (49%), flat or abnormal nose (79%), low or malformed ears, micrognathia (68%), and cleft lip or palate; ocular features such as proptosis (56%), ectropion, hypoplastic eyelids, microphthalmia, and cataracts; and deformities of digits and limbs such as rocker-bottom feet, among others. 2, 3, 9 Genital underdevelopment, unilateral renal agenesis, pulmonary hypoplasia, and congenital heart defects may also occur but are less common. 2 There is some heterogeneity in the phenotype because not all of these signs and symptoms are present in every baby.…”

Predicting the functional effect of compound heterozygous genotypes from large scale variant effect maps

“…six additional reports [20,[52][53][54][55][56] S4). To experimentally measure the functional impact of these allele combinations in our yeast assay, we constructed diploid strains harboring yPSAT1 allele combinations encoding the same pair of PSAT1 amino acid sequences as the human genotypes.…”

“…As in our previous study [39], we used our growth assay to functionally assess pairwise combinations of protein-coding variants across all reported unique patient (and carrier parent) genotypes available at the time (Additional File 1: Table S4). Since our previous study [39], six additional reports [28][29][30][64][65][66] have added descriptions of 20 new NLS2/PSATD patients and twelve unique genotypes to the disease literature (Additional File 1: Table S4). To experimentally measure the functional impact of these allele combinations in our yeast assay, we constructed diploid strains harboring yPSAT1 allele combinations encoding the same pair of PSAT1 amino acid sequences as the human genotypes.…”

Long-surviving Neu-Laxova syndrome confirmed by whole exome sequencing: a case report

“…early cases reported were diagnosed clinically and by histopathological examination and following the emergence of molecular genetic diagnosis in 2014 by WES. 1 Chromosomal microarray can detect only copy number changes (gains or losses), not gene mutations. This case illustrates the usefulness of molecular diagnosis by WES for a baby with multiple congenital abnormalities.…”