Phocomelia | |
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Cases of severe thalidomide-induced phocomelia. | |
Specialty | Teratology |
Phocomelia is a congenital condition that involves malformations of human arms and legs which results in a flipper-like appendage. [1] [2] A prominent cause of phocomelia is the mother's use of the drug thalidomide during pregnancy; however, the causes of most cases are to be determined. [2]
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.
The term is from Ancient Greek φώκη phōkē, "seal (animal)" + -o- interfix + μέλος melos, "limb" + ια -ia suffix). Phocomelia is an extremely rare congenital disorder involving malformation of the limbs (dysmelia). Étienne Geoffroy Saint-Hilaire coined the term in 1836. [3]
The symptoms of phocomelia syndrome are undeveloped limbs and absent pelvic bones; however, various abnormalities can occur to the limbs and bones. [4] 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. Sometimes hands or fingers will be present but limp due to having no bones or being loosely attached. 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 National Organization for Rare Disorders (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 (a condition known as micrognathia), and a cleft lip with cleft palate. [6] According to NORD, severe symptoms of phocomelia include:[ citation needed ]
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: [7]
The infants that were exposed to thalidomide during development phases had a 40% chance of survival. [8] The McCredie–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. [7]
Thalidomide was released onto the market in 1958 in West Germany under the name Contergan. Primarily prescribed as a sedative or hypnotic, thalidomide also claimed to cure "anxiety, insomnia, gastritis, and tension". [8] 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, i.e. it 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. Only 40% of these children survived. [8]
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. [9] 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 that the long limbs either were not developed or presented themselves as stumps. Other effects included deformed eyes, hearts, alimentary and urinary tracts, blindness and deafness. [10]
According to the 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]
A study of Roberts syndrome, a genetic disorder showing similar symptoms to phocomelia, has shed light on the possible causes. [11] An individual afflicted with Roberts Syndrome will have chromosome copies that do not connect at the centromeres, making them unable to line up accordingly. [12] 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.[ citation needed ]
Prosthesis is a synthetic alternative for missing limbs, teeth, and various other body parts. Advances in materials, pigments and manufacturing methods during the twentieth century have rendered artificial limbs lighter in weight and more realistic-looking. Myoelectric prostheses take all their input from the nervous system and muscles at the site of attachment in the form of electric signals. [13]
Children born with phocomelia are recommended to have a prosthetic mitten fitted to get used to the sensation of wearing an aid early on; typically a hook is added around the age of two years until the necessary tissues, bone structures, proprioception and motor coordination have developed to permit use of a myoelectric prosthetic limb.[ citation needed ]
Teratology is the study of abnormalities of physiological development in organisms during their life span. It is a sub-discipline in medical genetics which focuses on the classification of congenital abnormalities in dysmorphology caused by teratogens. Teratogens are substances that may cause non-heritable birth defects via a toxic effect on an embryo or fetus. Defects include malformations, disruptions, deformations, and dysplasia that may cause stunted growth, delayed mental development, or other congenital disorders that lack structural malformations. The related term developmental toxicity includes all manifestations of abnormal development that are caused by environmental insult. The extent to which teratogens will impact an embryo is dependent on several factors, such as how long the embryo has been exposed, the stage of development the embryo was in when exposed, the genetic makeup of the embryo, and the transfer rate of the teratogen.
A birth defect is an abnormal condition that is present at birth, regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can range from mild to severe. Birth defects are divided into two main types: structural disorders in which problems are seen with the shape of a body part and functional disorders in which problems exist with how a body part works. Functional disorders include metabolic and degenerative disorders. Some birth defects include both structural and functional disorders.
Weissenbacher–Zweymuller syndrome (WZS), also called Pierre-Robin syndrome with fetal chondrodysplasia, is an autosomal recessive congenital disorder, linked to mutations in the COL11A2 gene, which codes for the α2 strand of collagen type XI. It is a collagenopathy, types II and XI disorder. The condition was first characterized in 1964 by G. Weissenbacher and Ernst Zweymüller.
Primrose syndrome is a rare, slowly progressive genetic disorder that can vary symptomatically between individual cases, but is generally characterised by ossification of the external ears, learning difficulties, and facial abnormalities. It was first described in 1982 in Scotland's Royal National Larbert Institution by Dr D.A.A. Primrose.
The VACTERL association refers to a recognized group of birth defects which tend to co-occur. This pattern is a recognized association, as opposed to a syndrome, because there is no known pathogenetic cause to explain the grouped incidence.
Caudal regression syndrome, or sacral agenesis, is a rare birth defect. It is a congenital disorder in which the fetal development of the lower spine—the caudal partition of the spine—is abnormal. It occurs at a rate of approximately one per 60,000 live births.
Holt–Oram syndrome is an autosomal dominant disorder that affects bones in the arms and hands and often causes heart problems. The syndrome may include an absent radial bone in the forearm, an atrial septal defect in the heart, or heart block. It affects approximately 1 in 100,000 people.
Duane-radial ray syndrome, also known as Okihiro syndrome, is a rare autosomal dominant disorder that primarily affects the eyes and causes abnormalities of bones in the arms and hands. This disorder is considered to be a SALL4-related disorder due to the SALL4 gene mutations leading to these abnormalities. It is diagnosed by clinical findings on a physical exam as well as genetic testing and imaging. After being diagnosed, there are other evaluations that one may go through in order to determine the extent of the disease. There are various treatments for the symptoms of this disorder.
Amelia is the birth defect of lacking one or more limbs. The term may be modified to indicate the number of legs or arms missing at birth, such as tetra-amelia for the absence of all four limbs. The term is from Ancient Greek ἀ- 'lack of' and μέλος 'limb'.
Dysmelia is a congenital disorder of a limb resulting from a disturbance in embryonic development.
Congenital amputation is birth without a limb or limbs, or without a part of a limb or limbs.
3C syndrome is a rare condition whose symptoms include heart defects, cerebellar hypoplasia, and cranial dysmorphism. It was first described in the medical literature in 1987 by Ritscher and Schinzel, for whom the disorder is sometimes named.
Renal dysplasia-limb defects syndrome, also known as Ulbright–Hodes syndrome, is a very rare autosomal recessive congenital disorder. It has been described in three infants, all of whom died shortly after birth.
Hanhart syndrome is a broadly classified medical condition consisting of congenital disorders that cause an undeveloped tongue and malformed extremities and fingers. There exist five types of Hanhart syndrome, with the severity and nature of the condition ranging widely on a case-by-case basis. Hanhart syndrome is classified as a rare disease, with approximately 30 known cases having been reported between 1932 and 1991. Early hypotheses believed that the disorder was caused by genetic conditions, with a more recent hypothesis demonstrating that the disorder may be caused by hemorrhagic lesions during prenatal development. The causal mechanism behind this vascular disruption is still unknown.
Congenital hemidysplasia with ichthyosiform erythroderma and limb defects is a genetic disorder with onset at birth seen almost exclusively in females. The disorder is related to CPDX2, and also has skin and skeletal abnormalities, distinguished by a sharp midline demarcation of the ichthyosis with minimal linear or segmental contralateral involvement.
Roberts syndrome, or sometimes called pseudothalidomide syndrome, is an extremely rare autosomal recessive genetic disorder that is characterized by mild to severe prenatal retardation or disruption of cell division, leading to malformation of the bones in the skull, face, arms, and legs.
Constriction ring syndrome (CRS) is a congenital disorder with unknown cause. Because of the unknown cause there are many different, and sometimes incorrect names. It is a malformation due to intrauterine bands or rings that give deep grooves in, most commonly, distal extremities like fingers and toes. In rare cases the constriction ring can form around other parts of the fetus and cause amputation or even intrauterine death. The anatomy proximal to the site of constriction is developmentally normal. CRS can be associated with other malformations with club foot being most common. The precise configuration of the bands, lymphedema, and character of the amputations are not predictable and vary with each individual patient. Also, more than one extremity is usually affected, and it is rare for only one ring to present as an isolated malformation with no other manifestation of this syndrome.
13q deletion syndrome is a rare genetic disease caused by the deletion of some or all of the large arm of human chromosome 13. Depending upon the size and location of the deletion on chromosome 13, the physical and mental manifestations will vary. It has the potential to cause intellectual disability and congenital malformations that affect a variety of organ systems. Because of the rarity of the disease in addition to the variations in the disease, the specific genes that cause this disease are unknown. This disease is also known as:
XK aprosencephaly is an extremely rare congenital disorder characterized by the absence of the embryonic forebrain. Because the prosencephalon gives way to the cerebral cortex, survival with aprosencephaly is not possible outside utero. The external symptoms are similar to holoprosencephaly, a related disorder, including a smaller than normal head (microcephaly), small eyeballs (microphthalmia), a small mouth (microstomia), anal atresia, and abnormalities of the external genitalia, radius, nostrils, and pharynx (throat).
Hecht Scott syndrome is a rare genetic disease that causes congenital limb formation. The main characterisation is the aplasia or hypoplasia of bones of the limb. It is currently presenting in less than 1 in 1,000,000 newborns. It has been known to be more commonly present in males. It was first diagnosed in 2005 by Courtens et al. who recognised the malformations with his present case and four others that were similarly described in literature.
The word "phocomelia" means seal limb. It describes an extremely rare condition in which babies are born with limbs that look like flippers.