Galloway-Mowat syndrome in Taiwan: OSGEP mutation and unique clinical phenotype

Pei-Yi Lin,Shih-Hua Lin,Jeng-Daw Tsai,Martin Zenker,Min-Hua Tseng,Jui-Hsing Chang,Shuan-Pei Lin,Chun-Chen Lin,Friedhelm Hildebrandt,Jia Rao,Ming-Dar Lee,Chyong-Hsin Hsu

doi:10.1186/s13023-018-0961-9

Abstract

BackgroundGalloway-Mowat syndrome (GAMOS) is a rare autosomal recessive disease characterized by the combination of glomerulopathy with early-onset nephrotic syndrome and microcephaly with central nervous system anomalies. Given its clinical heterogeneity, GAMOS is believed to be a genetically heterogenous group of disorders. Recently, it has been reported that mutations in KEOPS-encoding genes, including the OSGEP gene, were responsible for GAMOS.ResultsOverall, 6 patients from 5 different Taiwanese families were included in our study; the patients had an identical OSGEP gene mutation (c.740G > A transition) and all exhibited a uniform clinical phenotype with early-onset nephrotic syndrome, craniofacial and skeletal dysmorphism, primary microcephaly with pachygyria, and death before 2 years of age. We reviewed their clinical manifestations, the prenatal and postnatal presentations and ultrasound findings, results of imaging studies, associated anomalies, and outcome on follow-up. All individuals were found to have an “aged face” comprising peculiar facial dysmorphisms. Arachnodactyly or camptodactyly were noted in all patients. Neurological findings consisted of microcephaly, hypotonia, developmental delay, and seizures. Brain imaging studies all showed pachygyria and hypomyelination. All patients developed early-onset nephrotic syndrome. The proteinuria was steroid-resistant and eventually resulted in renal function impairment. Prenatal ultrasound findings included microcephaly, intrauterine growth restriction, and oligohydramnios. Fetal MRI in 2 patients confirmed the gyral and myelin abnormalities.ConclusionsOur study suggests that a careful review of the facial features can provide useful clues for an early and accurate diagnosis. Prenatal ultrasound findings, fetal MRI, genetic counseling, and mutation analysis may be useful for an early prenatal diagnosis.

Highlights

Galloway-Mowat syndrome (GAMOS) is a rare autosomal recessive disease characterized by the combination of glomerulopathy with early-onset nephrotic syndrome and microcephaly with central nervous system anomalies
Galloway–Mowat syndrome (GAMOS) is a rare autosomal recessive disorder characterized by early-onset steroid-resistant nephrotic syndrome (SRNS) and microcephaly with brain anomalies [1]
All of our patients were born small for gestational age (SGA) at term or near-term (Patient IV, at 36 weeks and 6 days)

Summary

Introduction

Galloway-Mowat syndrome (GAMOS) is a rare autosomal recessive disease characterized by the combination of glomerulopathy with early-onset nephrotic syndrome and microcephaly with central nervous system anomalies. It has been reported that mutations in KEOPS-encoding genes, including the OSGEP gene, were responsible for GAMOS. Galloway–Mowat syndrome (GAMOS) is a rare autosomal recessive disorder characterized by early-onset steroid-resistant nephrotic syndrome (SRNS) and microcephaly with brain anomalies [1]. It was originally described in 1968 in two siblings with the triad of congenital nephrotic syndrome, microcephaly, and hiatus. Recent studies have unmasked important genetic mutations in some patients with GAMOS. Via whole exon sequencing and high throughput exon sequencing, Braun and colleagues identified mutations in Kinase, Endopeptidase and Other Proteins of small Size (KEOPS) complex genes responsible for GAMOS (OMIM *301006, *617729, *617730, *617731) [9]

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