Phocomelia syndrome

Definition

Phocomelia is a “congenital malformation” of development where the upper appendage of an arm or leg is absent so the hands or feet are attached to the body like stumps. The word phocomelia combines phoco—denoting seal and melia—denoting limb to signify a “limb like a seal’s flipper" [Medical Dictionary Online. 10 October 2007 .] Although various numbers of factors can cause phocomelia, the prominent roots come from the drug use of thalidomide and from genetic inheritance. The occurrence of this malformation in an individual results in various abnormalities to the face, limbs, ears, nose, vessels and many other underdevelopments. The best fix for phocomelia is prevention of a pregnant woman taking thalidomide during pregnancy and prosthesis. Although operations can be done to fix the abnormality it is difficult due to the lack of nerves, bones, and other related structures.

Causes

Thalidomide

Thalidomide is an “oral medication” prescribed today to cure certain skin conditions such as: leprosy, Behcet’s disease, dermatomyositis, and is currently being assessed for containment of HIV-related disease ["Thalidomide Article." 12 March 2001. MedicineNet.com. 10 October 2007 .] (Thalidomide Article). According to Diane Calabrase and Teresa Odle, other studies propose thalidomide “can slow or stop the spread of cancer of the brain, breast colon, prostate, as well as multiple myeloma” ["Thalidomide Article." 12 March 2001. MedicineNet.com. 10 October 2007 .] Although thalidomide has proven to be beneficial in many respects, if used during pregnancy, the effects on the fetus can be fatal.

History of Thalidomide

Thalidomide was released into the market in 1957 in West Germany under the label of Contergam. Primarily prescribed as a sedative or hypnotic, thalidomide also claimed: to cure “anxiety, insomnia, gastritis, and tension.” [Miller, Marylin T. "Thalidomide Embryopathy: A Model for the Study of Congenital Incomitant Horizontal Strabismus." Transaction of the American Ophthalmological Society (1991): 81; 623-674.] Afterwards it was used to combat against nausea and alleviate morning sickness in pregnant women. Thalidomide became an over the counter drug in Germany around 1960, and could be purchased without a prescription. Shortly after the drug’s selling, in Germany, between 5,000 and 7,000 infants were born with the qualities of phocomelia. ["Pharmaceutical Teratogens." Teratology Society--Birth Defects Research. 08 December 2007 .] Out of these children merely 40% of them survived. Research also proves that although phocomelia was non-existent through the 40’s and 50’s, by time the drug was released in Germany in the 60’s, cases of severe phocomelia amplified; the direct cause was linked to thalidomide. ["Pharmaceutical Teratogens." Teratology Society--Birth Defects Research. 08 December 2007 .] The statistic was given that “50 percent of the mothers with deformed children had taken thalidomide during the first trimester of pregnancy.” [Cuthbert, Alan. "Thalidomide." The Oxford Companion to the Body. Oxford University Press, 2001, 2003. Answers.com 06 Dec. 2007. http://www.answers.com/topic/thalidomide.] Throughout Europe, Australia, and the United States, 10,000 cases were reported of infants with phocomelia; only 50% of the 10,000 survived. [Cuthbert, Alan. "Thalidomide." The Oxford Companion to the Body. Oxford University Press, 2001, 2003. Answers.com 06 Dec. 2007. http://www.answers.com/topic/thalidomide.] Thalidomide became effectively linked to death or severe disabilities among babies. Those subjected to thalidomide while in the womb experienced limb deficiencies in away that the long limbs either weren’t developed or presented themselves as stumps. Other effects included: deformed eyes, hearts, alimentary, and urinary tracts, along with blindness and deafness. [Cuthbert, Alan. "Thalidomide." The Oxford Companion to the Body. Oxford University Press, 2001, 2003. Answers.com 06 Dec. 2007. http://www.answers.com/topic/thalidomide.]

Genetic inheritance

A genetic disease is inherited by an individual from the genes provided by their mother and father. Depending upon the grouping of these genes for a particular trait, determines whether or not an individual will inherit a certain disease. According to National Organization for Rare Dissorders (NORD): when phocomelia is transmitted [in its familial genetic form] it is seen as an autosomal recessive trait and the mutation is linked to chromosome 8 ["Phocomelia Syndrome." National Organization for Rare Disorders. 11 October 2007 .]

Recessive genetic disorders occur when a person receives identical “abnormal genes” from both the father and mother. ["Phocomelia Syndrome." National Organization for Rare Disorders. 11 October 2007 .] If a person inherits one normal gene and one gene for the disease, the individual will become a carrier for the disease; however, they normally do not show symptoms. The chance for two carrier parents to both supply the defective gene and produce a child with symptoms is 25 percent with each pregnancy. ["Phocomelia Syndrome." National Organization for Rare Disorders. 11 October 2007 .]

During normal cell division, each chromosome is replicated and the original chromosome is attached to the new copy. Although there are several attachment points in a chromosome, the centromere is the major connection point and where the immensity of the work generates. The chromosomes’ connection allows the cells to join together—making sure that the two copies are “lined up together at the center of the dividing cell.” [Vega, Hugo, et al. "FIFTEEN-YEAR HUNT UNCOVERS GENE BEHIND "PSEUDOTHALIDOMIDE" SYNDROME." 11 April 2005. John Hopkins Medicine. 10 December 2007 .] Once the chromosomes are aligned, tiny molecular spindles attach to each copy and then pull away the “original and new copy” as the division continues. [Vega, Hugo, et al. "FIFTEEN-YEAR HUNT UNCOVERS GENE BEHIND "PSEUDOTHALIDOMIDE" SYNDROME." 11 April 2005. John Hopkins Medicine. 10 December 2007 .] An individual containing phocomelia will have chromosome copies that do not connect at the centromeres, making them unable to line up accordingly. As a result, the cell becomes incapable of division or slow in the process; because of this the newly made cells contain an excessive or reduced amount of chromosomes. [Vega, Hugo, et al. "FIFTEEN-YEAR HUNT UNCOVERS GENE BEHIND "PSEUDOTHALIDOMIDE" SYNDROME." 11 April 2005. John Hopkins Medicine. 10 December 2007 .] In phocomelia the cells cease to develop or die—preventing proper development of the: limbs, eyes, brain, palate, or other structures. [Vega, Hugo, et al. "FIFTEEN-YEAR HUNT UNCOVERS GENE BEHIND "PSEUDOTHALIDOMIDE" SYNDROME." 11 April 2005. John Hopkins Medicine. 10 December 2007 .]

ymptoms

General symptoms

Typically the symptoms of phocomelia syndrome are undeveloped limbs and absent pelvic bones; however, various abnormalities can occur to the limbs and bones. [Olney RS, Hoyme HE, Roche F, Ferguson K, Hintz S, Madan A. "Limb/Pelvis Hypoplasia.Aplasia With Skill Defect (Schinzel Phocomelia): Distinctive Features And Prenatat Detection." Am J Med Genet 1 November 2001: 103(4): 295-301.] Usually the upper limbs are not fully formed and sections of the “hands and arms may be missing.” ["Phocomelia Syndrome." National Organization for Rare Disorders. 11 October 2007 .] Short arm bones, fused fingers, and missing thumbs will often occur. Legs and feet are also affected similarly to that of the arms in hands. Individuals with phocomelia will often experience missing thigh bones, and the hands or feet may be of an unordinary petite size or appear as stumps due to their close “attachment to the body.” ["Phocomelia Syndrome." National Organization for Rare Disorders. 11 October 2007 .] According to NORD, individuals carrying phocomelia syndrome will generally show symptoms of growth retardation previous to and after birth. The syndrome can also cause mental deficiencies in infants. Infants born with phocomelia will normally have a petite head with “sparse hair” that may appear “silvery-blonde.” ["Phocomelia Syndrome." National Organization for Rare Disorders. 11 October 2007 .] Hemangioma, the abnormal buildup of blood vessels, will possibly develop around the facial area at birth as and the eyes will be set distantly apart due to hypertelorism. The pigment of the eyes will be a bluish white. ["Phocomelia Syndrome." National Organization for Rare Disorders. 11 October 2007 .] Phocomelia can also cause: an undeveloped nose with slender nostrils, disfigured ears, irregularly petite jaws [also known as micrognathia] , and a cleft lip with cleft palate. [Hunt, Katherine Susan. "Roberts SC phocomelia." Gale Encyclopedia of Genetic Disorders, Part I . Detroit: The Gale Group Inc., 2002.] According to NORD, severe symptoms of phocomelia include:
*A fissure of the skull and a projecting brain known as (encephalocele)
*An accumulation of spinal fluid under the skull also known as drocephalus; causing vomiting and migraines
*An abnormally shaped uterus (bicornate)
*Inability to clot blood efficiently due to a low amount of platelets running through the blood
*Malformations in the kidney and heart
*Shortened neck
*Abnormalities in the urethra

Thalidomide syndrome symptoms

When an individual inherits phocomelia due to drugs or pharmaceuticals, it is known as thalidomide syndrome. The symptoms of thalidomide syndrome are defined by absent or shortened limbs; causing flipper hands and feet. According to Anthony J Perri III, and Sylvia Hsu they can additionally receive:
*Palsy disorder of the face
*Ear and eye abnormalities; resulting in limited/complete loss of hearing or sight
*Gastrointestinal and genitourinary tract disorders
*Ingrown genitalia
*Undeveloped/missing lungs
*Distorted digestive tract, heart, kidney The infants whose fetuses are exposed to thalidomide during development phases have a 40% chance of survival. [Miller, Marylin T. "Thalidomide Embryopathy: A Model for the Study of Congenital Incomitant Horizontal Strabismus." Transaction of the American Ophthalmological Society (1991): 81; 623-674.] The McMredie-McBride hypothesis explains that the limbs of the infants become malformed as a result to the thalidomide harming the neural tissue—simply because the neural tissue has such a large impact on formation and development of the limbs. [Perri, Anthony J III and Sylvia Hsu. "A Review of Thalidomides's History and Current Dermatological Applications." Dermatology Online Journal 9 (3): 5 (n.d.).]

Treatment

Prosthesis is a synthetic alternative for missing limbs, teeth, hearts, and various other body parts. Advances in prosthetic limbs have increased greatly during the twentieth century. The use of new materials such as: modern plastics, complex procedures, and better pigments have created lighter in weight and more realistic looking artificial limbs. With the advancement of myoelectric prosthetic limbs, patients are able to move their limbs without the use of cords or other devices. The myoelectric limbs can detect electric signals from the nervous system and muscles. They were first used on adults, but now they are being fitted to children. [Hunter, James. "An Ecternally Poertrf Prostheses for Unilateral Congenital Amelia." ICIB (1976): 1-4.] Patients that receive a loss of limbs due to phocomelia are typically treated with prosthetics. Infants at the age of 6 months are recommended to have a prosthetic mitten fitted to them; enabling them to get used to the prosthesis. A hook will be added when the child reaches the age of 2 years. Eventually the patient may receive a myoelectric prosthetic limb. Patients are treated in this way due to: the lack of understanding at a young age, the absence of necessary tissues and bones to hold the prosthesis together, and deficiency of sensory reaction from the patient. [Hunter, James. "An Ecternally Poertrf Prostheses for Unilateral Congenital Amelia." ICIB (1976): 1-4.] Other surgical alternatives relating to phocomelia include:
*Metacarpal transposition of the hand from the center to the edge
*Skeletal distraction techniques
*Bone distraction methods
*On-top plasty
*Nonvascularized phalangeal transfer from the foot
*Nonvascularized bone graft
*Vascularized toe-to-thumb transfersThese surgical alternatives are made difficult due to the non-existent nerves, bones, tendons, and related structures. ["Hand, Congenital Hand Deformities." 27 September 2006. emedicine. 15 October 2007 .]

Cases in humans

Mat Fraser

Fraser received phocomelia at birth due to his mother taking thalidomide while she was pregnant. He is known as the drummer of rock bands including: “Fear of Sex”, “The Reasonable Strollers,” “Joyride,” “The Grateful Dub,” and “Living in Texas.” He is also a notable actor and performing artist. Fraser has been seen on television as a host and an actor for many productions. [Seniorfitness.com. 10 December 2007 .]

Alison Lapper

Lapper was born with the “limb deficiency” phocomelia. Comparable to most people with the disorder, she was arm deficient and received shortened bones and legs. Despite her disability she graduated from Brighton University, mothered a healthy son, and established a life as a skilled artist. Lapper lives off of income from The Mouth and Foot Painter’s Association producing cards and calendars. ["Alison Lapper, The Woman with the Remarkable Body." 24 November 2007. ExtraOrdinary People. 10 December 2007 .] Lapper is quite independent and will not wear prosthetic limb. In 2003 she attended a Women and Disability Conference where she spoke about becoming a parent and motherhood. ["Alison Lapper, The Woman with the Remarkable Body." 24 November 2007. ExtraOrdinary People. 10 December 2007 .]

Other famous people

Other famous people containing phocomelia syndrome are: Thomas Quasthoff, a famous opera singer; Rick Renstrom, known for his abilities at the guitar; Hee Ah Lee famous for the piano due to only having two fingers on each hand; and Stanle Berent who made his living performing in “freak shows.” [Seniorfitness.com. 10 December 2007 .]

References