Galloway–Mowat syndrome

Galloway-Mowat Syndrome (GMS) is a rare genetic disorder characterized by the combination of microcephaly (abnormally small head size) and glomerulopathy (kidney disease), along with a spectrum of other potential neurological and physical abnormalities. First described in 1968 by Galloway and Mowat, the syndrome has since been identified in a small number of individuals worldwide, highlighting its rarity and the diversity of its presentation.

Symptoms and Diagnosis

The hallmark features of Galloway-Mowat Syndrome include severe microcephaly, nephrotic syndrome (a kidney disorder that causes the body to excrete too much protein in the urine), and significant developmental delays. Other possible symptoms can include hiatal hernia, epilepsy, intellectual disability, and distinctive facial features such as a prominent forehead, hypertelorism (widely spaced eyes), and micrognathia (small jaw).

Diagnosis of GMS is primarily based on clinical observation of its characteristic symptoms, supported by genetic testing. Advances in genetic sequencing technologies have facilitated the identification of mutations in several genes associated with the syndrome, notably in the WDR73 gene, which is thought to play a critical role in the development of the condition.

Genetics

Galloway-Mowat Syndrome is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected by the disorder. The identification of mutations in the WDR73 gene and others has been crucial in understanding the genetic basis of GMS, although not all cases can be explained by mutations in currently known genes, suggesting that further genetic heterogeneity exists within the syndrome.

Treatment and Management

There is no cure for Galloway-Mowat Syndrome, and treatment is symptomatic and supportive. Management of the renal aspects of the disease may include medications to control proteinuria (excess protein in the urine) and other symptoms of nephrotic syndrome. Neurological and developmental symptoms are managed according to individual needs, which may involve physical therapy, special education services, and seizure management.

Prognosis

The prognosis for individuals with Galloway-Mowat Syndrome varies widely, depending on the severity of kidney disease and neurological involvement. The syndrome can be life-limiting, particularly in cases where kidney disease progresses to end-stage renal failure. However, the course of the disease is highly variable, and some individuals may live into adulthood with appropriate management of their symptoms.

Research Directions

Research into Galloway-Mowat Syndrome is ongoing, with efforts focused on better understanding the genetic causes of the disease and how these genetic changes lead to the specific symptoms observed in affected individuals. There is also interest in developing more effective treatments for the renal and neurological aspects of the syndrome, which could significantly improve the quality of life for those affected.