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 malformations of the head and facial (craniofacial) area, such as an unusually small head (microcephaly) that appears flat at the top (vertex) and back (occiput); an abnormally high, narrow forehead; and/or widely spaced eyes (ocular hypertelorism). Some affected infants may also have unusually small jaw bones (micrognathia); a highly arched roof of the mouth (palate); and/or large, low-set ears.
In many infants with Galloway-Mowat Syndrome, part of the stomach may protrude through an abnormal opening (esophageal hiatus) 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). (The esophagus is the muscular passageway that brings food from the throat to the stomach.) 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 (larygospasm); an inflammatory condition of the lungs caused by the entrance of food particles into the respiratory passages (aspiration pneumonia); and/or additional respiratory complications. (For more information on Gastroesophageal Reflux, see the Related Disorders section below.)
Infants with Galloway-Mowat Syndrome may also have several kidney (renal) abnormalities. The kidneys may be unusually large (nephromegaly); have an increased number of cells (hypercellularity); and/or contain several small cysts (microcystic dysplasia). In addition, clusters of capillaries (renal glomeruli), which normally filter the blood that passes through the kidneys (glomeruli filtration), may be replaced by scar tissue (focal glomerulosclerosis). In some cases, the thin membrane supporting the loops of capillaries that make up the renal glomeruli may also be replaced by fibrous, hardened scar tissue (diffuse mesangial sclerosis).
The resulting loss of the renal glomeruli’s filtering ability causes the kidneys to function abnormally, and the affected individual exhibits a variety of symptoms (Nephrotic Syndrome) as a result. For example, the affected infant may excrete abnormally high levels of protein in the urine (proteinuria), specifically the protein albumin (albuminuria); 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 may 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).
Infants with Galloway-Mowat Syndrome may also exhibit various malformations of the brain. Affected infants may have an abnormally small brain (microencephaly), and the internal layer of the cerebellum, which controls the coordination of movement, may be missing. 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 infants with Galloway-Mowat Syndrome, 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 (pachygria). In other cases, the folds may be absent or incompletely formed (lissencephaly); as a result, the brain may have a smooth surface. (For more information on Lissencephaly, see the Related Disorders section below.)
Affected individuals may also exhibit absence or underdevelopment of myelin in various areas of the brain and spinal cord. Myelin, a substance made up of fatty (lipid) material and protein, enables effective transmission of nerve impulses through the brain and spinal cord by serving as an electrical insulator. In infants with Galloway-Mowat Syndrome, there may be an absence of myelin around nerve fibers in the cerebrum; there may also be underdevelopment of myelin (hypomyelination) in the spinal cord and/or brainstem.
Due to hypomyelination and/or the brain malformations described above, infants with Galloway-Mowat Syndrome may also exhibit neurological, neuromuscular, and/or developmental abnormalities. 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). (For more information on seizures, see Epilepsy in the Related Disorders section below.) Neuromuscular abnormalities may include diminished muscle tone throughout the body (generalized hypotonia); abnormally increased reflex reactions (hyperreflexia); poor ability to control movements of the head; and/or an inability to control hand, feet, and/or eye 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). Mental retardation is usually present.
Galloway-Mowat Syndrome is an extremely rare genetic disorder that is inherited as an autosomal recessive trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother.
In recessive disorders, the condition does not appear unless a person inherits the same defective gene for the same trait from each parent. If one 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 of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is twenty-five percent. Fifty percent of their children will be carriers, but healthy as described above. Twenty-five percent of their children will receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.
Galloway-Mowat Syndrome, which is also known as Microcephaly-Hiatal Hernia-Nephrotic Syndrome, is an extremely rare genetic disorder that affects males and females in equal numbers. Approximately 20 cases have been reported in the medical literature. Of the three main features associated with the disorder (microcephaly, hiatal hernia, and Nephrotic Syndrome), the unusual smallness of the infant’s head (microcephaly) will be obvious at birth (congenital); symptoms occurring during the first weeks after birth may indicate the presence of a hiatal hernia; and the symptoms associated with Nephrotic Syndrome may become apparent within days, weeks, months, or, in some cases, two or three years after birth.
Galloway-Mowat Syndrome, also known as Microcephaly-Hiatal Hernia-Nephrotic Syndrome, can be diagnosed after birth (postnatally) by a thorough clinical evaluation, characteristic physical findings, specialized laboratory tests, imaging techniques, and genetic testing. Of the three main symptoms associated with the disorder (microcephaly, hiatal hernia, and Nephrotic Syndrome), abnormalities of the head and facial (craniofacial) area, particularly the head’s extremely small size (microcephaly) and unusual shape, are obvious at birth.
Recurrent spitting up and forceful vomiting during the first few weeks after birth may lead to suspicion of hiatal hernia. The presence of a hiatal hernia may be confirmed by x-ray (radiographic) examination, visualization with an optic instrument (endoscopy), and/or measurement of fluid pressure within the esophagus (esophageal manometry).
In affected infants, symptoms associated with Nephrotic Syndrome may become apparent within days, weeks, months, or in some cases, two or three years after birth. Urinary analysis may reveal small traces of blood (hematuria) and abnormally high levels of protein (proteinuria), specifically albumin (albuminuria), in the urine. Additional laboratory studies may reveal unusually low levels of albumin in an affected individual’s blood (hypoalbuminemia). These findings, occurring in association with anemia and an abnormal accumulation of fluid that causes swelling (edema), may indicate a diagnosis of Nephrotic Syndrome. Microscopic examination (e.g., immunofluorescence and electron microscopy) of samples of kidney tissue (renal biopsy) may reveal renal abnormalities that may help to confirm a diagnosis of Nephrotic Syndrome, e.g., small cysts (microcystic dysplasia), an unusually large number of cells (hypercellularity), and/or abnormal deposits within and degeneration of portions of the kidneys due to the loss of the glomeruli’s filtering ability (focal glomerulosclerosis and/or diffuse mesangial sclerosis).
Treatment of Galloway-Mowat Syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, nephrologists, gastroenterologists, neurologists, surgeons, physical therapists, and/or others may need to work together to ensure a systematic, comprehensive approach to treatment.
Treatment for Nephrotic Syndrome in individuals with Galloway-Mowat Syndrome may include a low-sodium diet with low levels of protein. 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. In cases of renal failure, hemodialysis may be required to remove excess waste products from the blood.
For affected infants who also experience seizures, treatment may include therapy with anticonvulsant drugs to help prevent, reduce, or control seizures. Because individuals with Galloway-Mowat Syndrome 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. (For more information on therapies for the treatment of Epilepsy, choose “Epilepsy” as your search term in the Rare Disease Database.)
Genetic counseling is advised for families of children with Galloway-Mowat Syndrome. Other treatment is symptomatic and supportive.
Surgical removal of one or both kidneys (nephrectomy) has been used to treat individuals with early onset nephrotic syndrome. More research is necessary to determine the long-term safety and effectiveness of this potential treatment for individuals with conditions associated with early onset nephrotic syndrome such as Galloway-Mowat Syndrome.
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