NORD gratefully acknowledges Emma Baple, MBBS, MRCPCH, PhD, Consultant in Clinical Genetics, Senior Lecturer in Genomic Medicine, Genomics England Clinical Lead for Rare Disease Validation and Feedback, and Olivia Wenger, MD, Pediatrician, Medical Director, New Leaf Center, Clinic For Special Children, Mt. Eaton, Ohio, for assistance in the preparation of this report.
Galloway-Mowat syndrome is an extremely rare genetic disorder that is characterized by a variety of physical and developmental abnormalities, particularly neurological abnormalities and early onset progressive kidney disease. Physical features may include microcephaly, (a condition that indicates that the head circumference is significantly smaller than would be expected based upon an infant’s age and gender) and, in some cases, protrusion of part of the stomach through an abnormal opening in the diaphragm (hiatal hernia). Neurological abnormalities can include: various malformations of the brain, seizures, muscle spasms and abnormal movements (dystonia), diminished muscle tone throughout the body (generalized hypotonia), and visual impairment and abnormal eye movements (nystagmus). Infants and children exhibit a delay in obtaining developmental milestones. The majority of affected children do not obtain independent sitting or ambulation or the acquisition of any purposeful hand use or verbal communication. Severe/profound intellectual disability is typically present. Kidney disease is characterized by damage to the clusters of capillaries in the kidneys (focal glomerulosclerosis and/or diffuse mesangial sclerosis) resulting in loss of protein in the urine and abnormal kidney function with associated swelling of the face and peripheries resistant to current medical treatment (steroid resistant nephrotic syndrome). Most affected individuals do not survive beyond teenage years, with the commonest causes of death being nephrotic syndrome or seizures. Galloway-Mowat syndrome appears to be genetically heterogeneous and is believed to be inherited in an autosomal recessive manner, a significant proportion of cases identified to date have been shown to be caused by biallelic alterations (mutations) in the WDR73 gene.
Galloway-Mowat syndrome was first described in the medical literature in 1968 in two siblings who had microcephaly, hiatal hernia and kidney disease. Consequently, the disorder was also known as microcephaly-hiatal hernia-nephrotic syndrome. However, additional reports of this disorder have shown that affected individuals have neurological manifestations and kidney disease (nephrotic syndrome) as the main characteristics. Hiatal hernia is no longer considered a “key” feature of the disorder since it does not occur in many affected children.
In 2014, autosomal recessive loss of function mutations in the WDR73 gene were found to account for a significant proportion of Galloway-Mowat syndrome cases.
Please note that some of these organizations may provide information concerning certain conditions (e.g., Microcephaly, Hiatal Hernia, or Nephrotic Syndrome) potentially associated with this disorder.
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