Neonatal seizures, lissencephaly and abnormal genitalia – a case of XLAG-syndrome

X-linked lissencephaly with abnormal genitalia (XLAG) is a rare cause of severe, neonatal onset neurological disorder in boys. The syndrome is linked to mutations in the aristaless related homeobox gene (ARX). We report the case of a male newborn with typical features of XLAG. The boy presented with severe neonatal seizures refractory to treatment with four antiepileptic drugs so far, severe muscular hypotonia associated with hypoventilation, temperature instability, endocrine disturbances and exocrine pancreatic insufficiency. He has abnormal genitalia with micropenis and bilateral cryptorchism. Cerebral ultrasound and MRI showed absence of corpus callosum and pachygyria with a posterior-to-anterior gradient. A half-sister of our patient became symptomatic with muscular hypotonia and seizures at the age of 1 month. CT of the girl revealed absence of corpus callosum.

An insertion c.1206_1207insG was found in exon 4 of ARX on Xp22.3-p21.1 in our patient (hemizygous) and his mother (heterozygous). This leads to a frame-shift mutation, which has not been reported yet. The mother of both children showed no clinical or neuroradiological abnormalities.

Conclusions: Distinct morphological features and family history suggest the diagnosis of XLAG. Diagnosis can be confirmed by molecular genetics.