ABSTRACT
In some cases Neu-Laxova syndrome (NLS) is linked to serine deficiency due to mutations in the phosphoglycerate dehydrogenase (PHGDH) gene. We describe the prenatal and postnatal findings in a fetus with one of the most severe NLS phenotypes described so far, caused by a homozygous nonsense mutation of PHGDH. Serial ultrasound (US) and pre- and postnatal magnetic resonance imaging (MRI) evaluations were performed. Prenatally, serial US evaluations suggested symmetric growth restriction, microcephaly, hypoplasia of the cerebellar vermis, micrognathia, hydrops, shortened limbs, arthrogryposis, and talipes equinovarus. The prenatal MRI confirmed these findings prompting a diagnosis of NLS. After birth, radiological imaging did not detect any gross bone abnormalities. DNA was extracted from fetal and parental peripheral blood, all coding exons of PHGDH were PCR-amplified and subjected to Sanger sequencing. Sequencing of PHGDH identified a homozygous premature stop codon mutation (c.1297C>T; p.Gln433*) in fetal DNA, both parents (first-cousins) being heterozygotes. Based on previous associations of mutations in this gene with a milder NLS phenotype, as well as cases of serine deficiency, these observations lend further support to a genotype-phenotype correlation between the degree of PHGDH inactivation and disease severity.
Subject(s)
Abnormalities, Multiple/genetics , Brain Diseases/genetics , Carbohydrate Metabolism, Inborn Errors/genetics , Codon, Nonsense , Fetal Growth Retardation/genetics , Ichthyosis/genetics , Limb Deformities, Congenital/genetics , Microcephaly/genetics , Phenotype , Phosphoglycerate Dehydrogenase/deficiency , Phosphoglycerate Dehydrogenase/genetics , Psychomotor Disorders/genetics , Seizures/genetics , Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/pathology , Base Sequence , Brain Diseases/diagnosis , Brain Diseases/pathology , Carbohydrate Metabolism, Inborn Errors/diagnosis , Carbohydrate Metabolism, Inborn Errors/pathology , Consanguinity , Female , Fetal Growth Retardation/diagnosis , Fetal Growth Retardation/pathology , Fetus , Gene Expression , Genes, Lethal , Genetic Variation , Genotype , Homozygote , Humans , Ichthyosis/diagnosis , Ichthyosis/pathology , Infant, Newborn , Limb Deformities, Congenital/diagnosis , Limb Deformities, Congenital/pathology , Male , Microcephaly/diagnosis , Microcephaly/pathology , Molecular Sequence Data , Pedigree , Psychomotor Disorders/diagnosis , Psychomotor Disorders/pathology , Seizures/diagnosis , Seizures/pathology , Sequence Analysis, DNA , Severity of Illness Index , Ultrasonography, PrenatalABSTRACT
El síndrome de neu-laxova es una enfermedad genética, que se hereda como rasgo autosómico recesivo. Se caracteriza por retraso del crecimiento intrauterino, microcefalia, ictiosis, exoftalmos y edema generalizado, pero puede asociarse a cualquier tipo de malformaciones cutáneas y viscerales con atrofia o hipoplasia de todas las estructuras del cerebro, microgenitalismo, agenesia renal, hipoplasia pulmonar y mal formación cardiaca. La supervivencia máxima comunicada ha sido de seis semanas.El caso presentado, atendido en el hospital maternidad Enrique C. Sotomayor de Guayaquil, trata de recién nacido de sexo femenino. Se observó piel cubierta de placa escamosa amarillenta, brillante, además de malformaciones de extremidades y ectropión, con sobrevida de seis días. El eco transfontanelar reveló hipoplasia de las estructuras cerebrales.Conclusiones: En la mayoría de los casos reportados en la literatura médica, los padres han sido consanguíneos.Recomendaciones: La ultrasonografía nos permite obtener el diagnóstico prenatal.
The neu-laxova syndrome is a very strange genetic illness that is inherited like feature recessive autosómico. It is characterized by delay of the intra-uterine growth, microcephaly, congenital ichthyosis, exoftalmus and generalized edema, but it can be associated to any type of cutaneous and visceral malformations with atrophy or hipoplasia of all the structures of the brain. The survival rate of this illness is six weeks.The present case of a female infant obtained at the Enrique C. Sotomayor hospital in Guayaquil. We could observe the presence of congential ichthyosis, One observes skin covered with yellowish, brilliant scaly badge, besides malformations of limbs and ectropion. She lived for six days. The transcranic ecography revealed hipoplasy of the cerebral structures.Conclusions: In most of the cases reported in the medical literature the parents they have been consanguineous.Recommendations: The ultrasonography allows us to obtain the prenatal diagnosis.