X-linked lissencephaly with abnormal genitalia (XLAG) associated with renal phosphate wasting and exocrine pancreatic insufficiency

X-linked lissencephaly with abnormal genitalia (XLAG) is caused by loss-of-function mutations of the aristaless-related homeo-box (ARX) gene. The clinical picture is imperfectly delineated due to the small number of reported patients and death in 7 of 10 cases during the first 3 months. We report on a XLAG-patient with a 1bp-deletion (790delC) of the ARX-gene who also suffered from renal phosphate wasting and exocrine pancreatic insufficiency. This has not been described previously. An MRI of his clinically healthy mother being heterozygous for the mutation revealed agenesis of the corpus callosum. The boy displayed the characteristic clinical symptoms (micropenis and cryptorchism, secondary microcephaly, intractable epilepsy, chronic diarrhoea, temperature instability) and typical neuroradiological findings previously described in XLAG. A low serum phosphate was noticed since age 6 months and tubular phosphate reabsorption was found to be markedly reduced subsequently (48–55%). An adequate therapy was impossible due to episodes of chronic diarrhoea associated with exocrine pancreatic insufficieny as expressed by markedly reduced pancreatic elastase in stool. Demineralisation of bones progressed and rib fractures occurred. The boy died at age 18 months. We conclude that the clinical picture of XLAG may be broader than hitherto known and that it may include renal phosphate wasting and exocrine pancreatic insufficiency.

Keywords: XLAG, lissencephaly, abnormal genitalia, intractable epilepsy, renal phosphate wasting