About galloway mowat syndrome
What is galloway mowat syndrome?
Galloway-Mowat Syndrome, which is also known as Microcephaly-Hiatal Hernia-Nephrotic Syndrome, is an extremely rare genetic disorder that is characterized by a variety of physical and developmental abnormalities. Physical features may include an unusually small head (microcephaly) and additional abnormalities of the head and facial (craniofacial) area; damage to clusters of capillaries in the kidneys (focal glomerulosclerosis and/or diffuse mesangial sclerosis), resulting in abnormal kidney function (Nephrotic Syndrome); and, in many cases, protrusion of part of the stomach through an abnormal opening (esophageal hiatus) in the diaphragm (hiatal hernia). Additional physical abnormalities are often present. These may include various malformations of the brain, seizures, diminished muscle tone throughout the body (generalized hypotonia), and/or increased reflex reactions (hyperreflexia). Infants and children with Galloway-Mowat Syndrome may also exhibit developmental abnormalities including an inability to perform certain movement (motor) skills normal for their age and a profound delay in the attainment of skills requiring the coordination of muscular and mental activity (psychomotor retardation). Mental retardation may also be present. Galloway-Mowat Syndrome is inherited as an autosomal recessive trait.
What are the symptoms for galloway mowat syndrome?
Physical abnormalities symptom was found in the galloway mowat syndrome condition
Although researchers have been able to establish a syndrome with characteristic or “core” symptoms, much about the disorder is not fully understood. Several factors including the small number of identified cases, the lack of large clinical studies, and the possibility of other genetic causes aside from WDR73 and other yet undiscovered genetic factors influencing the disorder, have prevented physicians from developing a complete picture of associated symptoms and prognosis. Some researchers believe that Galloway-Mowat syndrome represents a clinically and genetically heterogeneous group of disorders, which means disorders that have different underlying causes (e.g. different aberrant genes), but that result in the same symptoms or spectrum of symptoms. Consequently, the specific symptoms present and overall severity can vary greatly from one person to another.
It is important to note that affected individuals will not have all of the symptoms discussed below and every affected individual is unique. Galloway-Mowat syndrome can, in some instances, be associated with life-threatening complications very early in life. Parents should talk to the physician and medical team about their child’s specific case, associated symptoms and overall prognosis.
Physical features may include malformations of the head and facial (craniofacial) area including microcephaly, which can be present at birth or develop shortly after birth, an abnormally high, narrow forehead and unusually small jaw bones (micrognathia). The head may appear flat at the top (vertex) and back (occiput). Abnormalities affecting the eyes may also occur including optic atrophy, a condition characterized by Degeneration of the optic nerve, which transmit information from the retina of the eye to the brain.
In some infants, part of the stomach may protrude through an abnormal opening where the esophagus passes through the diaphragm (hiatal hernia). As a result, the muscle that joins the esophagus and the stomach (esophagogastric junction) may not function appropriately, and there may be low pressure or inappropriate relaxation of the band of muscle fibers that closes the opening of the esophagus (lower esophageal sphincter). This allows the stomach’s acidic contents to flow back into the esophagus (gastroesophageal reflux). Such gastroesophageal reflux may cause affected infants to spit up and/or vomit repeatedly; in some cases, Vomiting may be particularly forceful (projectile vomiting). Affected infants may fail to thrive due to the resulting loss of necessary calories and nutrients. Gastroesophageal reflux may also cause Inflammation of the esophagus (esophagitis); choking; closure of the larynx due to sudden, violent laryngeal contractions (laryngospasm); an inflammatory condition of the lungs caused by the entrance of food particles into the respiratory passages (aspiration pneumonia); and/or additional respiratory complications.
Affected infants may also have kidney (renal) abnormalities that may be present at birth (congenital) or not develop until later in childhood. The kidney function becomes progressively impaired, and the kidneys excrete high levels of protein in to the urine (nephrotic syndrome), specifically, the protein albumin (albuminuria). This means that affected children have unusually low levels of albumin remaining in the blood (hypoalbuminemia); and exhibit anemia, weakness, an accumulation of fluid in the abdominal cavity (ascites), and/or an abnormal accumulation of fluid between layers of tissue under the skin (edema), particularly around the eye sockets (periorbital edema) and in the lowermost parts of the body, such as the ankles (dependent edema). The kidneys eventually lose their ability to excrete waste products through the urine, to regulate the balance of salt and water in the body, and to perform their other vital functions (renal failure). Affected individuals do not respond to the standard treatments for nephrotic syndrome and symptoms and disease progression worsen with intercurrent infections such as viral cold and flu.
Infants with Galloway-Mowat syndrome may also exhibit various malformations of the central nervous system. Neurological symptoms can precede the development of kidney abnormalities. Affected infants may have an abnormally small brain (microcephaly) at birth, or this can develop/progress as they get older. The cerebellum, which controls the coordination of movement, may be smaller than normal. The outer layer of the brain (cerebral cortex), which is responsible for conscious movement and thought, normally consists of several deep folds (gyri) and grooves (sulci). However, in some affected infants, the outer layer of the brain may have folds that are abnormally small (microgyria), or there may be a reduced number of folds that are larger than normal (pachygyria). In other cases, the folds may be absent (agyria) or incompletely formed (lissencephaly); as a result, the brain may have a smooth surface.
Neurological features may include a lack of response to stimuli in the environment and/or episodes of uncontrolled electrical Disturbances in the brain that may cause convulsions, spasms, and/or other symptoms (seizures). Neuromuscular abnormalities may include Diminished muscle tone throughout the body (generalized hypotonia); poor ability to control movements of the head; and/or an inability to control hand, feet, and/or eye movements, Muscle Spasms and Abnormal movements of the limbs (dystonic and choreiform movements). DevelopMental abnormalities in affected infants and children may include an inability to perform certain movement (motor) skills normal for their age (e.g., sitting up, crawling, walking, and other developmental milestones) and a profound delay in the attainment of skills requiring the coordination of muscular and mental activity (psychomotor retardation). Severe Intellectual disability is often present.
Additional symptoms and physical features have been described in specific cases including skeletal malformations such as underdeveloped nails, clubfeet, fingers that stuck or fixed in a bent position (camptodactyly), shortening of muscle tissue and tendons in a joint, forcing the joint into a flexed or bent position (flexion contractures), malformation of the central canal of the spinal cord, underdevelopment of the thyroid and/or adrenal glands, replacement of diaphragmatic muscle tissue with fibroelastic tissue that can cause displacement of the diaphragm (eventration of the diaphragm). A brain malformation known as Dandy-Walker malformation (DWM) has been reported in a few specific cases.
Individuals with Galloway-Mowat syndrome as a result of mutations in the WDR73 gene appear to have a core set of features which include: progressive microcephaly, cerebellar Atrophy (progressive shrinking of the cerebellum), generalized hypotonia, severe/profound psychomotor impairment and Intellectual disability and progressive nephrotic syndrome. Seizures of different types that are difficult to control and Dystonia and choreiform movements have been frequently observed.
What are the causes for galloway mowat syndrome?
In 2014, Galloway-Mowat syndrome was shown to be caused by alterations (mutations) in the WDR73 gene in a subset of cases. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, or absent. Depending upon the functions of the particular protein, this can affect many organ systems of the body.
Galloway-Mowat syndrome is consistent with autosomal recessive inheritance. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Recessive genetic disorders occur when an individual inherits the same altered gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
Although the WDR73 gene has been shown to cause Galloway-Mowat syndrome is certain cases, researchers believe that additional, as-yet-unidentified genes may cause the disorder in other cases (genetic heterogeneity).
What are the treatments for galloway mowat syndrome?
Treatment is directed toward the specific symptoms that are apparent in each individual and may require the coordinated efforts of a team of specialists. Pediatricians, kidney specialists (nephrologists), gastroenterologists, neurologists, surgeons, physical therapists, and/or other healthcare professionals may need to work together to ensure a systematic, comprehensive approach to treatment. Genetic counseling may be of benefit for affected individuals and their families.
Treatment for nephrotic syndrome may include a low-sodium diet with low levels of protein, albumin infusion, and vitamins, thyroid and mineral supplementation. The edema associated with nephrotic syndrome may be treated with medications that promote the excretion of urine (diuretics). Drug therapy may also include antibiotics to help fight infection. Treatment with corticosteroids and/or immunosuppressive drugs has not been effective for nephrotic syndrome associated with Galloway-Mowat syndrome. In cases that progress to renal failure, hemodialysis may be required to remove excess waste products from the blood. Dialysis is a procedure in which a machine is used to perform some of the functions of the kidney – filtering waste products from the bloodstream, helping to control blood pressure, and helping to maintain proper levels of essential chemicals such as potassium. End-stage renal disease is not reversible so individuals will require lifelong dialysis treatment or a kidney transplant.
What are the risk factors for galloway mowat syndrome?
Galloway-Mowat syndrome affects males and females in equal numbers. More than 70 cases have been reported in the medical literature. Because cases may go misdiagnosed or undiagnosed, determining the true frequency of Galloway-Mowat syndrome in the general population is difficult. There is a WDR73 founder mutation present at high frequency in the Old Order Amish population, leading to an increased frequency of Galloway-Mowat syndrome within this population.
Is there a cure/medications for galloway mowat syndrome?
Early intervention services are important in ensuring that affected children reach their potential. Special services that may be beneficial include special remedial education, physical therapy, speech therapy, and/or other medical, social, and/or vocational services. Additional treatment for this disorder is symptom specific and supportive. Specific symptoms associated with Galloway-Mowat syndrome are treated by routine, accepted guidelines. Surgery may be necessary for certain symptoms such as hiatal hernia. Therapy with anti-seizure (anticonvulsant) drugs may be prescribed for affected individuals who experience seizures to help prevent, reduce, or control seizures. Because affected individuals may be receiving other drugs that may prohibit the use of certain anticonvulsant medications, each patient’s case must be thoroughly coordinated by the physician team to determine the most appropriate therapies for each group of symptoms.