Thanatophoric dysplasia, also referred to as thanatophoric dwarfism, is a form of skeletal dysplasia characterized by abnormal skeletal growth and development which occurs in approximately 1 in 20,000 to 50,000 births, according to the National Institute of Health. Of the more than 380 forms of skeletal dysplasia, thanatophoric dysplasia is the most common form that is lethal in the neonatal period.
Types
Thanatophoric dysplasia, or TD, is a skeletal disorder characterized by severe limb shortening and abnormal bone development. The disorder is divided into two subtypes, based on clinical features. Type I is the most common form and is clinically defined based on the presence of a normal skull and curved long bones, such as the femur bones of the leg. Type 2 is characterized by a cloverleaf-shaped skull and straight femurs.There is clinical overlap among the two subtypes in the many other structural abnormalities that exist with this disorder.
Symptoms
Thanatophoric dysplasia is characterized by a multitude of skeletal abnormalities caused by disturbances in bone growth and development. The most noticeable feature of TD is the severe shortening of the arms and legs, overlaid by extra folds of skin. Severe respiratory problems are present and are caused by a narrowed, bell-shaped chest and underdeveloped lungs.The development of the skull is affected, resulting in macrocephaly, a condition in which the head is abnormally large. Also, the face and nose are flat in appearance and the eyes widely spaced.
Causes
Thanatophoric dysplasia is caused by a spontaneous genetic mutation. The mutation is in the fibroblast growth factor receptor-3 gene, or FGFR3, which makes a protein that is responsible for bone and brain tissue maintenance and development. In thanatophoric dysplasia, the FGFR3 gene is overactive, producing excess amounts of protein which causes disturbances in bone growth and development. Because the mutation is spontaneous, TD does not run in families and having a child with TD does not increase the chances of having another child with TD.
Diagnosis
Diagnosis of TD occurs most often during the second or third trimester using a prenatal ultrasound test. Physicians look for distinguishing features of TD, such as growth deficiencies, bowed femurs, and an enlarged head, but must be careful to rule out other conditions and disorders that are genetically related to TD. After birth, diagnosis is often through physical examination and radiographic imaging techniques. Sometimes it might be necessary to perform pathological analysis of tissue samples to confirm a diagnosis of TD.
Treatment
The majority of infants with thanatophoric dysplasia are either stillborn or die soon after birth from respiratory failure. Treatment can be either aggressive or palliative, depending on the severity of the disorder and the parents' desires. Aggressive treatment is aimed at preventing the respiratory distress associated with the disorder with mechanical breathing machines in the intensive care unit. Palliative treatment is focused on keeping the newborn infant comfortable until death. When diagnosed prenatally, it is also very important to monitor the mother's progress to avoid any complications during pregnancy.
