Distal arthrogryposis syndrome

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Distal arthrogryposis syndrome

Definition

Distal arthrogryposis syndrome is a rare genetic disorder in which affected individuals are born with a characteristic bending at the joints of the hands and feet. A contracture is the word used to describe what happens at the joints to cause this bending. In addition to contractures of the hand and feet, individuals with distal arthrogryposis are born with a tightly clenched fist and overlapping fingers.

Description

The word arthrogryposis means a flexed (bent) or curved joint. Distal means the furthest from any one point of reference or something that is remote. Therefore, distal arthrogryposis syndrome causes the joints at the most remote parts of our limbs, the hands and feet, to be flexed.

Consistent fetal movement during pregnancy is necessary for the development of the joints. Without regular motion, the joints become tight resulting in contractures. The first cases of arthryogryposis were identified in 1923. Arthryogryposis multiple congenital (AMC) is also referred to as fetal akinesia/hypokinesia sequence that is not a disorder, but describes what happens when there is no fetal movement during fetal development. The reasons for lack of fetal motion include neurologic, muscular, connective tissue, or skeletal abnormalities or intrauterine crowding. There are various disorders that involve some form of arthrogryposis.

Distal arthrogryposis was identified as a separate genetic disorder in 1982. Two types of distal arthrogryposis have been identified. Type 1 or typical distal arthrogryposis, is used to describe individuals with distal contractures of the hands and feet, characteristic positioning of the hands and feet, and normal intelligence. Type 2 distal arthrogryposis is known as the atypical form. It is characterized by additional birth defects and mild intellectual delays.

There are other syndomes which include arthrogryposis, however distal arthrogryposis has been characterized as its own syndrome by its inheritance pattern. In addition to the inheritance pattern, there are other features that differentiate this type of arthrogryposis from other forms. Some of these features include a characteristic position of the hands at birth; the fists are clenched and the fingers are bent and overlapping. In addition, problems with the positioning of the feet, called clubfoot is often seen in these individuals. Another distinguishing characteristic is an extremely wide variability in the severity and number of joint contractures someone may exhibit. This variability is often noticed between two affected individuals from the same family.

Genetic profile

Distal arthrogryposis syndrome is inherited in an autosomal dominant manner. Autosomal dominant inheritance patterns only require one genetic mutation on one of the chromosome pairs to exhibit symptoms of the disease. Chromosomes are the structures that carry genes. Genes are the blueprints for who we are and what we look like. Humans have 23 pairs, or 46 total chromosomes in every cell of their body. The first 22 chromosomes are numbered 1–22 and are called autosomes. The remaining pair is assigned a letter either an X or a Y and are the sex determining chromosomes. A typical male is described as 46, XY. A typical female is 46, XX.

Each parent contributes one of their paired chromosomes to their children. Before fertilization occurs, the father's sperm cell divides in half and the total number of chromosomes reduces from 46 to 23. The mother's egg cell undergoes the same type of reduction as well. At the time of conception, each parent contributes 23 chromosomes, one of each pair, to their children. All of the genetic information is contained on each chromosome.

If either the father or the mother is affected with distal arthrogryposis, there is a 50% chance they will pass on the chromosome with the gene for this disease to each of their children. The specific gene for distal arthrogryposis is not known, however we do know that it is located on chromosome number 9.

The symptoms of distal arthrogryposis can be different between two affected relatives. For example, a mother may have contractures in all of her joints, but her child may only be affected with contractures in the hands. Because of this variability in the symptoms of this disease, it is believed there is more than one gene mutation that causes distal arthrogryposis. As of 2001, the only gene thought to cause this disease is on chromosome number 9. The exact location and type of genetic mutation on chromosome 9 is not known and therefore, the only genetic testing available as of 2001 is research based.

Demographics

Distal arthrogryposis can affect individuals from all types of populations and ethnic groups. This disease can affect both males and females. There have been only a handful of individuals described with this type of arthrogryposis. The physician, Dr. Hall, who named the disorder in 1982, had initially identified 37 patients with type 1 and type 2 distal arthrogryposis syndrome. She identified 14 individuals with type 1 and 23 individuals with type 2. Since then, numerous other individuals have been diagnosed with distal arthrogryposis. The exact incidence has not been reported in the literature.

Signs and symptoms

At birth, many individuals have been diagnosed based on their characteristic hand positioning. Virtually all individuals with distal arthrogryposis are born with their hands clenched tightly in a fist. The thumb is turned inwards lying over the palm, called abduction. The fingers are also overlapping on eachother. This hand positioning is also characteristic of a more serious condition called trisomy 18 . The majority of patients with distal arthrogryposis will also have problems with the positioning of their feet. Many patients will have some form of clubfoot, where the foot is twisted out of shape or position. Another word for clubfoot is talipes.

In addition to the hand and foot involvement, a small percentage of patients will have a dislocation or separation of the hip joint as well as difficulty bending at the hips and tendency for there to be a slight degree of unnatural bending at the hip joints. The knees may also exhibit similar problems of being slightly bent and fixed at that point. Few individuals are born with stiff shoulders.

Type 2 distal arthrogryposis syndrome includes other birth defects not seen in type 1 individuals. For example, type 2 distal arthrogryposis involves problems with the closure of the lip called cleft lip or an opening in the roof of the mouth called cleft palate.

Other abnormalities seen in type 2 distal arthrogryposis include a small tongue, short stature, a curvature of the spine, more serious joint contractures, and mental delays.

Diagnosis

The diagnosis of distal arthrogryposis can sometimes be made during pregnancy from an ultrasound evaluation. An ultrasound may detect the characteristic hand finding as well as the flexion deformities of both the hands and the feet. An affected fetus may have difficulty swallowing and this is exhibited on an ultrasound evaluation as extra amniotic fluid surrounding the baby called polyhydramnios. Another very important and specific diagnositic sign for distal arthrogryposis during a pregnancy is no fetal movement. Ultrasound findings have been detected as early as 17 weeks of a pregnancy.

After birth, a diagnosis is made by a physician performing a physical examination of a baby suspected of having this disorder. If a baby is affected with type 2 distal arthrogryposis, they may have a difficult time eating properly. As of 2001, the only type of genetic testing available is research based. Because there is likely more than one gene that causes the disease, the genetic testing being performed at this time is not yet offered to affected individuals in order to confirm a diagnosis.

Treatment and management

The treatment for individuals with distal arthrogryposis is adjusted to the needs of the affected child. With therapy after birth to help loosen the joints and retrain the muscles, most individuals do remarkably well. The hands do not remain clenched an entire lifetime, but will eventually unclench. Sometimes the fingers will remain bent to some degree. Clubfoot can usually be corrected so that the feet can be positioned to be straight.

Prognosis

The prognosis depends on how severely affected an individual is and how many joints are involved. Some of the more severe cases may be associated with an early death due to sudden respiratory failure and difficulty breathing properly. The majority of individuals with distal arthrogryposis do very well after receiving the necessary therapies and sometimes surgery to correct severe joint contractions.

Resources

BOOKS

Fleischer, A., et al. Sonography in Obstetrics and Gynecology, Principles & Practice. Stamford, Conn.: 1996.

Jones, Kenneth. Smith's Recognizable Patterns of Human Malformation. 5th ed. Philadelphia: W.B. Saunders Company, 1997.

PERIODICALS

Sonoda, T. "Two brothers with distal arthrogryposis, peculiar facial appearance, cleft palate, short stature, hydronephrosis, retentio testis, and normal intelligence: a new type of distal arthrogryposis?" American Journal of Medical Genetics. (April 2000): 280–85.

Wong, V. "The spectrum of arthrogryposis in 33 Chinese children." Brain Development. (April 1997): 187–96.