What Is Galloway-Mowat Syndrome

Galloway-Mowat syndrome is a neurodegenerative disease which manifests as a set of physical and developmental malformations. Neurodegenerative disease occurs when the nerve cells which are present in the brain and periphery of the body stop functioning properly and eventually die which results in physical and developmental abnormalities in the affected individual^1.  

It is a very rare disease and the symptoms can present from anywhere between birth and early childhood, depending on the severity of the condition. It is important to seek medical help if any symptoms are noted in infants, to receive proper and prompt management and in this article, we will highlight the main features and more important information needed to understand this syndrome better. 

Causes and genetics 

Galloway-Mowat syndrome is caused by genes not working properly and these aberrations of genes are called mutations. In this disease, the aberrations are seen in a particular gene (WDR73 gene).²

Genes make up the genetic material in our bodies which is called DNA and each DNA has its role to play in the body. Some DNA play an important role in building the foundation of some proteins which are essential for the proper building, development and functioning of the human body. If there is a mutation in the genes, the subsequent proteins are also not built properly and thus the functioning of the body is impaired which presents as physical and mental malformations. 

Furthermore, it is an autosomal recessive syndrome, which means that you have to inherit the mutated gene from both parents for the disease to manifest. If you inherit only one mutated gene from one parent and a normal gene from the other parent, you will not show symptoms for the disease but you will carry this mutation in your genes and you could pass it on to your offspring. The chances of two parents who both carry this gene have a 25% chance of giving birth to a child affected with this syndrome and a 50% chance of their children being carriers. The incidence of males and females inheriting this disease is the same³

It is, therefore, imperative that there is genetic testing and counselling available to those individuals and families who have this disease or carry it in their genes. Genetic testing can be carried out simply using some blood or saliva from the individual and the results are also available relatively quickly, within a few weeks. The NHS offers free genetic testing and counselling if the person has been referred by a doctor.⁴

Clinical features⁵

The clinical features of this syndrome are usually seen in infants or from birth. Listed below are some of the common clinical features associated with Galloway-Mowat syndrome and brief descriptions to explain them further: 

• Cognitive impairment: this is one of the most common symptoms of this syndrome and is nearly always present in the affected  individual. There are problems associated with remembering, memory and thinking and often impaired intellectual ability.
• Delayed development: this is another common symptom and it describes a delay in infants reaching their milestones, such as a delay in speech, motor and social skills. The infant may not be able to properly control their hands, legs and heads and may not be able to reach normal milestones like walking, sitting, crawling etc. There may be diminished muscle tone throughout the body (hypotonia) and spasms or seizures as well.
• Microcephaly and brain changes: Often the infant's head will be smaller in size than is normal for their age group. The head might also be unusually flat at the top and back with an underdeveloped jaw (micrognathia). An MRI might reveal an abnormally small cerebellum and abnormal outer folds of the brain.
• Hypoplasia of ear cartilage: this means that often the ear cartilage will be underdeveloped.
• Renal abnormalities: the kidneys are not able to function properly and they excrete large amounts of protein in the urine and this is known as nephrotic syndrome. In particular, the protein albumin, is excreted and this creates a deficit of this protein in the blood; this condition is called hypoalbuminemia. This results in swelling, which can be found all over the body and especially around the eyes (periorbital edema) and in the lower part of the legs (dependent edema). Unfortunately, the nephrotic syndrome associated with this condition does not respond to normal treatments and the kidney function gets worse over time until it completely stops and eventually leads to renal failure. 
• Hiatus hernia: another frequent symptom is the presence of a hiatus hernia in which there is an abnormal opening in the part where the esophagus passes through the diaphragm and the upper part of the stomach starts to protrude from this abnormal opening. When this happens, the muscle which is present at the junction between the stomach and the esophagus does not function properly and it allows food and water to flow back into the esophagus. This presents as reflux or vomiting in an infant which is often repeated and sometimes the vomit is projected with considerable force; this is known as projectile vomiting. The repeated reflux might irritate the lining of the esophagus and cause it to swell which may lead to choking. The infant may have poor weight gain and growth and exhibit an overall failure to thrive due to nutrients not being able to stay in their stomach long enough to get digested. Some food particles may also enter the airways and cause respiratory problems such as pneumonia.  

• Optic atrophy: in some cases there may be degeneration of the optic nerve. The optic nerve is responsible for relaying information from the retina in the eye, to the brain and when this mechanism is hindered due to atrophy, it can lead to visual impairment or blindness. 
• Other symptoms: there are several other symptoms which may be present in varying frequencies in this syndrome. There may be malformations in the fingers such as underdeveloped nails and the fingers might also be stuck in a flexed position. There may also be short tendons and muscles found at various joints along the body, which can cause a permanently flexed position at the joints. Several other bones are also affected such as the spinal cord which could be underdeveloped and other organs, such as the adrenal gland or thyroid gland, may also be underdeveloped, causing more deficiencies in the body. 

Diagnosis 

There is no specific test to diagnose galloway-mowat syndrome; rather it is diagnosed by the presence of a few key symptoms present in the infant. These symptoms include the typical physical appearance of the infant (as described in the symptoms section) and the presence of microcephaly and nephrotic syndrome. Urine and blood tests are needed to confirm the presence of nephrotic syndrome; the urine tests would show abnormally high levels of the protein albumin ( albuminuria) and consequently the blood tests would show a low level of this protein in the blood, since it is being excessively excreted in the urine. There would be low levels of healthy red blood cells (anemia) as well. An MRI can also be done to reveal the typical changes in the brain associated with the disease. These tests, along with presence of swelling all over the body 

would be indicative of nephrotic syndrome and combined with other typical symptoms of this disease, galloway-mowat syndrome can be diagnosed.³ 

Treatment³

There is no specific treatment for this syndrome but each case needs to be individually evaluated and treatment plans need to be drawn up according to each symptom which appears in the individual. Usually, a multidisciplinary team of doctors will draw up a management plan. Since normal drugs used for nephrotic syndrome will not be effective in this syndrome, it can be managed by a diet low in protein, an infusion of albumin and vitamins, minerals and thyroid supplements. Antibiotics can be used to treat any infections and a drug which helps excrete fluid from the body (diuretics) through urine, can be used to manage the swelling.

If the kidney disease progresses to renal failure, life-long dialysis will be necessary. Dialysis is when a machine is used to “clean” the blood and maintain blood pressure, a function which is usually carried out by the kidneys. 

Anticonvulsants can be used to treat the seizures associated with this syndrome and surgery might be needed to treat hiatal hernia. 

Prognosis, research and support

Unfortunately, the prognosis for this syndrome is poor and most infants have a short life expectancy ^3..The earlier the onset of nephrotic syndrome, the more likely it is that the infant will have a shorter life expectancy.

At present, there seems to be limited research and clinical trials being conducted regarding this syndrome, and this could simply be due to how rare its occurrence is. More research is needed in order to understand and manage this syndrome better, as there is currently no specific treatment available for it. There is also no established way to prevent galloway-mowat syndrome, other than genetic testing and counseling for families and individuals who carry this gene. However, there have been reports of more research and, thus, more effective treatments to possibly become available for the affected individuals by 2022-2029 6.

People who are suffering, or have infants who are suffering from this syndrome, should be offered lots of information, full support and an excellent management plan in order to address each of the symptoms.