Phocomelia

Cases of severe thalidomide-induced phocomelia.

Phocomelia manifest as aural abnormalities.

Eyesight limitation from phocomelia.

Phocomelia (from Ancient Greek φώκη phōkē, "seal (animal)" + -o- interfix + μέλος melos, "limb" + English suffix -ia) is an extremely rare congenital disorder involving malformation of the limbs (dysmelia). Étienne Geoffroy Saint-Hilaire coined the term in 1836.^[1]

Although many factors can cause phocomelia, the prominent roots come from the use of the drug thalidomide and from genetic inheritance. Occurrence in an individual results in various abnormalities to the face, limbs, ears, nose, vessels and many other underdevelopments. Although operations may improve some abnormalities, many are not surgically treatable due to the lack of nerves and other related structures.

Causes

Thalidomide

Thalidomide was released onto the market in 1958 in West Germany under the label of Contergan. Primarily prescribed as a sedative or hypnotic, thalidomide also claimed to cure "anxiety, insomnia, gastritis, and tension".^[2] Afterwards it was used against nausea and to alleviate morning sickness in pregnant women. Thalidomide became an over-the-counter drug in Germany around 1960 and could be bought without a prescription. Shortly after the drug was sold, in Germany, between 5,000 and 7,000 infants were born with phocomelia. Merely 40% of these children survived. Research also proves that although phocomelia did exist through the 1940s and 1950s, cases of severe phocomelia multiplied in the 1960s, when thalidomide was released in Germany; the direct cause was traced to thalidomide.^[3] The statistic was given that "50 percent of the mothers with deformed children had taken thalidomide during the first trimester of pregnancy." Throughout Europe, Australia, and the United States, 10,000 cases were reported of infants with phocomelia; only 50% of the 10,000 survived. Thalidomide became effectively linked to death or severe disabilities among babies. Those subjected to thalidomide while in the womb experienced limb deficiencies in a way that the long limbs either were not developed or presented themselves as stumps. Other effects included: deformed eyes, hearts, alimentary, and urinary tracts, and blindness and deafness.^[4]

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 Disorders (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.^[5]

Recessive genetic disorders occur when a person receives identical "abnormal genes" from both the father and mother. 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.^[5]

A study of Roberts Syndrome, a genetic disorder showing similar symptoms to phocomelia, has shed light on the possible causes.^[6] 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 pair, the centromere is the major connection point and is primarily responsible for anchoring the chromosome pair together. The chromosomes' connection makes sure that the two copies are lined up together at the center of the dividing cell. Once the chromosomes are aligned, tiny molecular spindles attach to each centromere and then pull away the original and new chromosome as cell division continues. In this way, each daughter cell inherits one of each pair of replicated chromosomes. An individual afflicted with Roberts Syndrome will have chromosome copies that do not connect at the centromeres, making them unable to line up accordingly. As a result, the newly made cells contain an excess or reduced number of chromosomes. In both Roberts Syndrome and phocomelia the cells cease to develop, or die, preventing proper development of the limbs, eyes, brain, palate, or other structures.

Symptoms

General symptoms

The symptoms of phocomelia syndrome are undeveloped limbs and absent pelvic bones; however, various abnormalities can occur to the limbs and bones.^[7] Usually the upper limbs are not fully formed and sections of the "hands and arms may be missing." Short arm bones, fused fingers, and missing thumbs will often occur. Legs and feet are also affected similarly to the arms and hands. Individuals with phocomelia will often lack thigh bones, and the hands or feet may be abnormally small or appear as stumps due to their close "attachment to the body."^[5] According to NORD, individuals carrying phocomelia syndrome will generally show symptoms of growth retardation previous to and after birth. The syndrome can also cause severe mental deficiencies in infants. Infants born with phocomelia will normally have a petite head with "sparse hair" that may appear "silvery-blonde." Hemangioma, the abnormal buildup of blood vessels, will possibly develop around the facial area at birth and the eyes may be set widely apart, a condition known as orbital hypertelorism. The pigment of the eyes will be a bluish white.^[5] 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.^[8] 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 hydrocephalus; causing vomiting and migraines
• An abnormally shaped uterus (bicornuate)
• 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 is born with 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
• disorders to the limbs

The infants that were exposed to thalidomide during development phases had a 40% chance of survival.^[2] The McMredie-McBride hypothesis explains that the limbs of the infants become malformed as a result of the thalidomide harming the neural tissue—simply because the neural tissue has such a large impact on formation and development of the limbs.^[9]

Treatment

Prosthesis is a synthetic alternative for missing limbs, teeth, 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.^[10] 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; 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 and the absence of necessary tissues and bones to hold the prosthetic limb.

Notable people with phocomelia syndrome

• Sealo, the "Seal Boy"
• Matthias Buchinger
• Nick Vujicic was born without arms or legs.
• Mat Fraser was born with phocomelia 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 an actor and performing artist.^[11]
• Alison Lapper was born with phocomelia. She is arm deficient and has shortened bones and legs. Lapper graduated from Brighton University in 1994, established herself as a visual artist, and in 2000 gave birth to a son, Parys. Lapper produces cards and calendars for The Mouth and Foot Painter's Association. She does not wear prosthetic limbs.^[12]
• Ronan Tynan was born with phocomelia. He became a track and field athlete, competing in the 1984 and 1988 Summer Paralympics. Tynan went on to a career as a physician, and later, a singer.
• Ame Barnbrook was born without arms and only the lower half of her left leg.^[13] She has a rarer form of phocomelia, meaning all of her limbs are affected. Barnbrook plays the trumpet with her foot (she has three toes) and sails a SKUD18^[14] at world championship level. Barnbrook is currently training for the 2016 Rio Paralympics after missing out on qualifying for London 2012. She graduated from the University of Wollongong with a Bachelor of Creative Arts.
• Thomas Quasthoff, an opera singer;
• Eli Bowen, who made his living performing in sideshows;^[15] and Hee Ah Lee, a pianist who has two fingers on each hand.

References

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