Galloway–Mowat syndrome: An early-onset progressive encephalopathy with intractable epilepsy associated to renal impairment. Two novel cases and review of literature

Abstract

Galloway-Mowat Syndrome (GMS) is an autosomal recessively inherited condition which manifests with severe encephalopathy, featuring microcephaly, developmental delay, and early-onset intractable epilepsy. Patients typically show also renal involvement from the onset. We report two siblings with GMS presenting with early-onset, intractable epilepsy and neurological deterioration, later followed by renal impairment. In both patients intractable epilepsy started during the first months of life and included a combination of spasms, focal and myoclonic/atonic seizures, along with psychomotor retardation and dysmorphic features. One of the patient died from fulminating renal failure at age 6 years. The other patient developed only isolated proteinuria from the age 3 years. Our cases differ from 'classic' GMS, as manifested the clinical and laboratory features of renal involvement only some years later the onset of epilepsy and neurological symptoms. Therefore, the diagnosis of GMS should be considered in infants with intractable epilepsy, encephalopathy, and multiple neurological deficits, also in absence of renal manifestations. The literature data about the electroclinical features of epilepsy in GMS are also reviewed.

Extending the mutation spectrum for Galloway–Mowat syndrome to include homozygous missense mutations in the WDR73 gene

“…There was also intrafamilial variability as one sibling in the family suffered from epilepsy while the other was seizure‐free. Epilepsy was also observed previously in some patients with GMS, prior to gene discovery [Pezzella et al, ].…”

“…Other common pathologies observed in cranial MRI were thinning of corpus callosum in half of the patients and brain stem hypoplasia in 80%. These findings were reported only rarely in GMS patients [Pezzella et al, ]. These frequent additional findings may also be considered features of WDR73‐ mutated patient when GMS is in the differential diagnosis.…”

“…All WDR73‐ mutated patients displayed severe intellectual disability in contrast to variable intellectual disability of GMS patients reported prior to gene discovery [Pezzella et al, ]. The difference in severity may be attributed to the effects of overlapping epilepsy, additional neurodevelopmental brain anomalies, and optic atrophy in this subgroup.…”

“…Microcephaly is reported at the time of birth or noted later in life, frequently accompanied by cerebellar and corpus callosal hypoplasia, neural migration defects, and other brain malformations. Epilepsy and intellectual disability are also common [Meyers et al, ; Pezzella et al, ; Ekstrand et al, ]. Prenatal and perinatal findings include low birth weight, intrauterine growth retardation, oligohydramnios, mild facial dysmorphisms that can largely be attributed to the decrease in head circumference, hiatal hernia, joint contractures, and eye malformations such as microphthalmia, optic atrophy, and corneal opacities [Hou and Wang, ; Meyers et al, ; Chen et al, ].…”

A genetic diagnostic approach to infantile epileptic encephalopathies

“…Notes and references [19][20][21][22][23][24][25][26][27][28][29][30] 1p36 deletion Distinctive facial features. Often have structural brain abnormalities, congenital heart defects, eye/ vision problems, hearing loss, skeletal anomalies, abnormalities of the external genitalia, and renal abnormalities.…”