Genetic Causes of Intellectual Disabilities: Rubinstein-Taybi Syndrome (RTS) and Tay-Sachs disease
Rubinstein-Taybi syndrome (RTS) is named after two physicians. Dr. Jack Rubinstein and Dr. Hooshang Taybi first identified this rare disorder in 1963. Only 1 in 300,000 individuals develop the disorder. It affects males and females equally. The cause of RTS is presently unknown. Cases of RTS are sporadic and random.
There are no medical tests used to identify RTS. It is identified by a pediatrician or a geneticist based on physical and behavioral features. The telltale features are not necessarily present from birth. Therefore, they may go unnoticed for months, even years. For example, people who have the condition are commonly short in stature, but this is not apparent at birth. The babies are usually born of average weight and height but fail to grow at a normal rate. The delay in the growth rate continues into adolescence.
Facial features common to RTS include eyes that are spaced widely apart. The eyelids are droopy and eyes slant downward. The eyes tend to cross. The nose is pronounced with a wide nasal bridge. The head and the lower jaw are smaller than average. The palate often has a high arch. Hair tends to be thick and low-lying on the brow. Children with RTS also tend to have broad thumbs and broad first toes.
Individuals with RTS have skeletal abnormalities. These abnormalities cause problems with gross motor skills. Coordination and balance are affected. Children often have difficulty breathing and/or swallowing.
Children with RTS tend to be happy and amiable. They sometimes engage in self-soothing behaviors like rocking or spinning in circles. However, this is not the norm. They are rarely treated for hyperactivity. However, short attention span can be a significant problem.
Tay-Sachs disease is named after Warren Tay and Bernard Sachs. Dr. Tay was an ophthalmologist who documented a case in which an infant patient had an odd red spot on the retina. Dr. Sachs was a neurologist. He described cellular abnormalities and familial links associated with this novel disorder.
Tay-Sachs disease is an inherited disorder. It is most commonly found among people of eastern European Jewish (Ashkenazim) decent. The disorder is fatal in children. Life expectancy does not surpass five years of age. The disorder's cause is genetic. It involves the absence of hexosaminidase A (Hex A). This is an enzyme responsible for metabolizing GM2 ganglioside, a fatty acid/lipid. Without Hex A, GM2 builds up in cells with toxic effects. When this lipid accumulates, cell damage occurs. This damage mostly affects the brain and the nervous system. Genetic testing prior to pregnancy can determine if prospective parents they carry the genetic marker.
Cell damage to brain and the nervous system begins during fetal development. However, the condition is not apparent at birth. Babies appear normal for the first several months of life. Symptoms can differ. Sometimes there is a slowing of normal development and a loss of peripheral vision. Children do not react appropriately to sensory stimulation. For example, they may overreact to sounds. Seizures and deteriorating mental functioning are apparent within the first two years of life.
As the disorder progresses, babies begin to lose previously mastered skills. This includes crawling, turning over, and reaching. After a time, blindness ensues. Gradually, the child becomes unable to move and is unresponsive. Ultimately, the infant becomes unable to breathe or swallow.
Presently there is no cure for Tay-Sachs disease. Sadly, there are no successful treatments for symptoms. Research studies are investigating the possibility of using replacement therapies to provide the missing Hex-A gene or the missing enzyme. One of the biggest obstacles researchers face is finding a way to get the brain to accept the enzyme.