Galloway-Mowat syndrome (GAMOS) is a rare autosomal recessive disorder characterized by nephrotic syndrome and central nervous system (CNS) abnormalities, namely microcephaly.
Galloway-Mowat syndrome is considered extremely rare. Approximately 40 cases have been reported worldwide 1.
Typically, microcephaly and CNS abnormalities are present from birth, with associated severe psychomotor impairment and seizures. However, microcephaly may occur later in development 1. Treatment-resistant nephrotic syndrome generally presents in the third month of life, but albuminuria may be present from birth 1.
Five monogenic mutations have been implicated in the pathogenesis of Galloway-Mowat syndrome. WD repeat-containing protein 73 (WDR73), which is a critical scaffold component of protein-complex assembly, was the first to be identified 1,2. Recently, mutations in four genes encoding the four subunits of the kinase, endopeptidase and other proteins of small size (KEOPS) complex have been identified in 32 families affected by Galloway-Mowat syndrome 3. KEOPS is essential to the function of transfer RNA and therefore protein translation and cell growth 4. The exact mechanism of pathogenesis is unclear.
A range of structural CNS changes have been reported, including gross abnormalities of cerebral parenchyma - cerebral atrophy, encephalomalacia, porencephaly - and defects in neuronal migration - agyria, microgyria, polymicrogyria 1.
Treatment and prognosis
There is no treatment for Galloway-Mowat syndrome 1. Affected individuals may survive for one year 1.
- 1. Jinks RN, Puffenberger EG, Baple E, Harding B, Crino P, Fogo AB, Wenger O, Xin B, Koehler AE, McGlincy MH, Provencher MM, Smith JD, Tran L, Al Turki S, Chioza BA, Cross H, Harlalka GV, Hurles ME, Maroofian R, Heaps AD, Morton MC, Stempak L, Hildebrandt F, Sadowski CE, Zaritsky J, Campellone K, Morton DH, Wang H, Crosby A, Strauss KA. Recessive nephrocerebellar syndrome on the Galloway-Mowat syndrome spectrum is caused by homozygous protein-truncating mutations of WDR73. (2015) Brain : a journal of neurology. 138 (Pt 8): 2173-90. doi:10.1093/brain/awv153 - Pubmed
- 2. Colin E, Huynh Cong E, Mollet G, Guichet A, Gribouval O, Arrondel C, Boyer O, Daniel L, Gubler MC, Ekinci Z, Tsimaratos M, Chabrol B, Boddaert N, Verloes A, Chevrollier A, Gueguen N, Desquiret-Dumas V, Ferré M, Procaccio V, Richard L, Funalot B, Moncla A, Bonneau D, Antignac C. Loss-of-function mutations in WDR73 are responsible for microcephaly and steroid-resistant nephrotic syndrome: Galloway-Mowat syndrome. (2014) American journal of human genetics. 95 (6): 637-48. doi:10.1016/j.ajhg.2014.10.011 - Pubmed
- 3. Braun DA, Rao J, Mollet G, Schapiro D, Daugeron MC, Tan W, Gribouval O, Boyer O, Revy P, Jobst-Schwan T, Schmidt JM, Lawson JA, Schanze D, Ashraf S, Ullmann JFP, Hoogstraten CA, Boddaert N, Collinet B, Martin G, Liger D, Lovric S, Furlano M, Guerrera IC, Sanchez-Ferras O, Hu JF, Boschat AC, Sanquer S, Menten B, Vergult S, De Rocker N, Airik M, Hermle T, Shril S, Widmeier E, Gee HY, Choi WI, Sadowski CE, Pabst WL, Warejko JK, Daga A, Basta T, Matejas V, Scharmann K, Kienast SD, Behnam B, Beeson B, Begtrup A, Bruce M, Ch'ng GS, Lin SP, Chang JH, Chen CH, Cho MT, Gaffney PM, Gipson PE, Hsu CH, Kari JA, Ke YY, Kiraly-Borri C, Lai WM, Lemyre E, Littlejohn RO, Masri A, Moghtaderi M, Nakamura K, Ozaltin F, Praet M, Prasad C, Prytula A, Roeder ER, Rump P, Schnur RE, Shiihara T, Sinha MD, Soliman NA, Soulami K, Sweetser DA, Tsai WH, Tsai JD, Topaloglu R, Vester U, Viskochil DH, Vatanavicharn N, Waxler JL, Wierenga KJ, Wolf MTF, Wong SN, Leidel SA, Truglio G, Dedon PC, Poduri A, Mane S, Lifton RP, Bouchard M, Kannu P, Chitayat D, Magen D, Callewaert B, van Tilbeurgh H, Zenker M, Antignac C, Hildebrandt F. Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly. (2017) Nature genetics. 49 (10): 1529-1538. doi:10.1038/ng.3933 - Pubmed
- 4. Perrochia L, Guetta D, Hecker A, Forterre P, Basta T. Functional assignment of KEOPS/EKC complex subunits in the biosynthesis of the universal t6A tRNA modification. (2013) Nucleic acids research. 41 (20): 9484-99. doi:10.1093/nar/gkt720 - Pubmed