Galloway Mowat syndrome

Overview

Galloway-Mowat syndrome (GAMOS) is a rare and severe genetic disorder that affects multiple organ systems, primarily the brain and kidneys. It is characterized by early-onset nephrotic syndrome (a kidney disorder leading to excessive protein loss in urine), along with microcephaly (an abnormally small head), developmental delays, and neurological abnormalities. First described in the 1960s by Galloway and Mowat, this syndrome typically presents in infancy and often leads to significant morbidity and early mortality.

Causes

Galloway-Mowat syndrome is caused by mutations in several genes involved in cellular structure and function, most notably:

• WDR73

• LAGE3

• KEOPS complex genes (OSGEP, TP53RK, TPRKB)

These genes play critical roles in maintaining the stability of microtubules and regulating gene transcription, which are essential for both brain development and kidney function. The syndrome is inherited in an autosomal recessive manner, meaning both parents must be carriers of the mutated gene for a child to be affected.

Symptoms

The clinical features of GAMOS can vary, but common symptoms include:

• Congenital or early-onset nephrotic syndrome

• Microcephaly and brain atrophy

• Severe developmental delay and intellectual disability

• Hypotonia (reduced muscle tone)

• Seizures

• Facial dysmorphism (e.g., wide nasal bridge, micrognathia)

• Abnormal brain MRI findings such as cerebellar hypoplasia

• Failure to thrive

In many cases, symptoms begin during the first few months of life and progressively worsen over time.

Diagnosis

Diagnosis of Galloway-Mowat syndrome involves a combination of clinical, imaging, and genetic approaches:

• Clinical evaluation: Observation of characteristic features such as microcephaly, nephrotic syndrome, and developmental delay

• Neuroimaging: MRI showing cerebral atrophy, cerebellar hypoplasia, or other structural anomalies

• Urinalysis: Detection of proteinuria indicating nephrotic syndrome

• Genetic testing: Whole exome sequencing or targeted gene panels to identify pathogenic mutations

• Renal biopsy: May reveal diffuse mesangial sclerosis or other glomerular abnormalities

Treatment

There is no cure for Galloway-Mowat syndrome, and treatment is primarily supportive and aimed at managing symptoms. Common interventions include:

• Nephrotic syndrome management: Use of ACE inhibitors, diuretics, and dietary protein control

• Seizure control: Antiepileptic medications

• Physical and occupational therapy: To address developmental delays and hypotonia

• Nutritional support: To promote growth and manage failure to thrive

• Multidisciplinary care: Including nephrology, neurology, genetics, and developmental specialists

In some cases, renal transplantation may be considered, although it is not commonly performed due to the severity of neurological involvement.

Prognosis

The prognosis for individuals with Galloway-Mowat syndrome is generally poor. Most affected children experience progressive neurological deterioration and renal failure. Life expectancy is significantly reduced, with many patients not surviving beyond early childhood. However, prognosis can vary depending on the specific genetic mutation and severity of organ involvement. Early diagnosis and comprehensive supportive care can help improve quality of life and extend survival in some cases.