Ambiguous genitalia associated with an extremely rare syndrome: a case report of xlag syndrome and review of the literature

Prasenjit Das,Vk Paul ,Prashant Ramteke,Tarun Kumar,Brijnandan Gupta

doi:10.5146/tjpath.2017.01391

Prasenjit Das, Vk Paul + Show 3 more

Open Access

https://doi.org/10.5146/tjpath.2017.01391

Copy DOI

Abstract

X-linked lissencephaly, absent corpus callosum, and epilepsy of neonatal onset with ambiguous genitalia comprises the XLAG syndrome and only 15 cases have been reported in literature. Due to its rarity, the exact clinical course and outcome are not known. Exact associations of this disease are also elusive. Hereby we are reporting this extremely rare entity and we searched the English literature extensively to get consolidated knowledge regarding this entity that would help the readers. Pre-natal radiological work-up can detect these malformations, which should be followed by medical termination, counseling and karyotyping. Till date the longest survival noted was 4 years only.

Highlights

The syndrome of X-linked lissencephaly, absent corpus callosum, epilepsy of neonatal onset with ambiguous genitalia (XLAG syndrome) was first described by Dobyns et al in 1999, who reported a lissencephaly with a posteriorto-anterior gradient, i.e. a posterior agyria and anterior pachygyria [1]
Gestational ultrasound and MRI are often diagnostic for the XLAG syndrome
The MRI findings are agyria with an increased thickness of the cerebral cortex, with three abnormal layers, including gray and white matters (6-7 mm) and complete agenesis of the corpus callosum

Summary

INTRODUCTION

The syndrome of X-linked lissencephaly, absent corpus callosum, epilepsy of neonatal onset with ambiguous genitalia (XLAG syndrome) was first described by Dobyns et al in 1999, who reported a lissencephaly with a posteriorto-anterior gradient, i.e. a posterior agyria and anterior pachygyria [1]. This rare genetic disease occurs due to mutation of the ARX homeobox gene (Xp 22.13). This gene is situated around the ventricles, neocortex, hippocampus and can be seen in the pancreas and testes [2]. The blood sample was sent for karyotyping but this could not be accomplished due to cell degeneration

Autopsy Findings

DISCUSSION

Index case