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Phocomelia

Non-Syndromic Limb Hypoplasia

Phocomelia is a condition listed under the category of congenital abnormalities. Patients with phocomelia lack the proximal sections of their extremities or exhibit underdeveloped sections, and the hands or foot are attached to the trunk without the intermediate segments of the limb.


Presentation

A variety of symptoms are associated with phocomelia. The most prominent and standard are those related to the underdevelopment of the extremities and skeleton [8]. The following characteristics are typical of phocomelia:

  • Complete lack of extremities
  • Segmental absence of extremities
  • Underdeveloped hands and feet, attached directly to the torso
  • Syndactyly
  • Absence of thumbs
  • Comprehensive growth retardation and deformed or absent pelvic bones
  • Cleft palate or lip

Individuals affected by the condition may sometimes be mentally hindered [9] and bear eyes that are located at a greater distance to each other, when compared to healthy individuals; the latter is known as orbital hypertelorism. Hemangiomas on the face, short nose and an abnormally small jaw may also be parts of the clinical picture. Often, newborns have small heads and reduced hair volume that seems silvery-colored.

Workup

Suspicion in the direction of phocomelia can arise during pregnancy when the standard ultrasonographic evaluation is carried out; the latter is a dependable examination to detect deformities as early as possible. No further genetic or other laboratory tests have been developed and the condition is postnatally diagnosed via a clinical examination. 

Treatment

There is no cure for Phocomelia, as it is a syndrome involving severe congenital deformities. Treatment aims primarily at correcting the specific anomalies that can be treated, symptomatic management, lifestyle adaptations, cognitive training and psychological support [10].

Deformities of the face, such as a cleft palate, can be surgically repaired from a very young age. Procedures vary depending on each case and include non-vascular bone grafting, separation of joint fingers, transfer of foot phalanges to the hand and many other techniques. Prosthetics can be used to compensate for the limb absence; such devices have evolved increasingly during the past decades and modern materials have rendered them friendlier and more effective. Myoelectric prosthetics have also been introduced to the market, which respond to the person's muscle movements and allow for an almost natural motion.

Family support and psychological support are also of vital importance. Patients are encouraged to opt for a prosthetic device as early as possible, so that the child will better adapt to the artificial limb. An impressive number of individuals with Phocomelia exhibit complete capability to adapt and perform everyday tasks or work. Mental retardation is not always a finding, but should be addressed with cognitive training when present.

Prognosis

Thalidomide use during gestation has been associated with a high risk of giving birth to a child with phocomelia, but also with reduced rates of embryonic survival. Extreme cases of cellular dysfunction and failure of the embryo to produce basic structures needed for its survival will lead to prenatal death in 60% of the cases. Phocomelia per ce is not associated with any other type of life-threatening condition or complication. Considerable deformity may pose everyday functional challenges to the young patient, as well as acceptance issues. Prosthetic devices have been greatly upgraded during the past years and can certainly help to facilitate everyday routine habits in people affected by phocomelia.

Etiology

Patients with Phocomelia have an autosomal recessive pattern of inheritance. Mutations in genes of the chromosome 8p21 have been identified as the cause [1].

On the other hand, thalidomide ingestion by expectant mothers has been proven to lead to the manifestation of the condition in an embryo. Thalidomide was developed during the 1950s and since 1960 it can be purchased without prescription. It is used as an anti-anxiety medication and also to treat morning sickness early in the course of a woman's pregnancy. However, during the first months of pregnancy, extremities are known to develop in an embryo, a process with is heavily hindered by thalidomide, leading to phocomelia or a complete absence of limbs, underdeveloped thumbs or a union between two fingers or toes (syndactyly).

Epidemiology

Phocomelia is a medical entity that is not very often encountered in the clinical practice; epidemiologic data remain scarce. However, an extensive study encompassing the observation of more than 1,000,000 newborns [2], calculated its prevalence at approximately 4 in 100,000. Other attempts to establish the international prevalence of a more comprehensive disorder group, including phocomelia, calculated this comprehensive prevalence to be 0.5 to 4.5 per 100,000 live births [3] [4] [5].

In general, congenital anomalies of the extremities are observed in around 0.5 per 100,000 live births [6]. Half of them are located on the hand or arm.

Sex distribution
Age distribution

Pathophysiology

Phocomelia results in a clinical picture that may vary greatly, although the pathophysiologic mechanisms underlying the disease are, generally, common. Patients may exhibit a segmental or total lack of extremities (meromelia and Amelia respectively), and in some cases underdeveloped hands or feet may protrude directly from the torso. Another distinct type of the disorder involves the presence of all four limbs, which are, however, pathologically short and small [7]. The latter is known as micromelia. 

The fundamental pathophysiologic alteration responsible for the condition are related to cellular division impairment. In phocomelia patients, chromosomal duplicates fail to establish centromeral connections and thus, they are unable to assume the proper position for division to occur at the metaphase stage. Chromatin concentration in the cells is abnormally low or high, a fact which greatly impedes division and leads to underdeveloped cells or cells with a reduced life circle length. As a result, limbs, brain and various other organs and structures fail to develop in an embryo.

With regard to thalidomide complications, the drug is a known cause of phocomelia. It has been proposed that it leads to an increased rate of cellular apoptosis, either by activating the caspase pathway or by inhibiting angiogenesis. A definitive answer concerning the exact pathogenetic mechanisms is yet to be established. 

Prevention

Avoiding the ingestion of thalidomide during pregnancy is a strict restriction that all mothers-to-be should abide by, given that the drug is known to cause phocomelia. Although there is no other specific measure in order to prevent the condition, good obstetrical care can help to diagnose deformities early during pregnancy and good health maintenance from the mother's side always helps to prevent various congenital abnormalities.

Summary

Phocomelia is a rare condition. Its name is derived from the Greek "phocia"= seal + "melos"= limb, due to the characteristic seal-like appearance of underdeveloped hands and feet. Truephocomelia involves the lack of the proximal sections of the extremities, where the hands or feet are immediately connected to the torso. Another type of phocomelia, an incomplete abnormality, includes underdeveloped intermediate sections of the extremities. The lower segments of the limbs, either hands or feet, may be fully developed or embryonic as well.

Phocomelia may be caused by a plethora of genetic mutations, passed on to the infant via an autosomal recessive pattern, or may be a spontaneous occurrence. Another known culprit for the development of phocomelia is the drug thalidomide, that was widely used in the 1950s to manage pregnancy-induced morning sickness, cough and for sedative purposes. In the years to come, approximately 5,000-7,000 pregnant women who were treated with the drug early in the course of their pregnancy gave birth to children with phocomelia; of the latter, less than half survived. 

With the advent of imaging techniques and other tests used to monitor the embryo prior to birth, phocomelia can be detected during the 12th week of pregnancy, either via amniocentesis or ultrasonography, even though a definitive method of diagnosis is yet to be found.

Regarding the treatment, phocomelia is an incurable abnormality. Prosthetics have been used to ameliorate the patients' standards of living and functionality.

Patient Information

Phocomelia is a condition which involves underdeveloped limbs amongst other symptoms. Its name comes from the Greek "phocia" (seal) + "melos" (limb), due to the characteristic seal-like appearance of underdeveloped hands and feet.

The condition can be inherited. The gene responsible for it is a recessive one, which means that both parents have to be carriers, in order for a newborn to have 25% possibility of being born with the disease. Another possible cause of phocomelia is the drug thalidomide. Thalidomide has been extensively used in the past as a medication to ease anxiety, as well as a drug to alleviate morning sickness during pregnancy. It has been found to cause phocomelia in newborns and women are presently discouraged from using it during the course of their pregnancy.

An individual affected by phocomelia typically exhibits strangely developed arms, hands, legs and feet. All four extremities may be missing; in other cases, some sections of the limbs are absent and underdeveloped hands or feet are attached to the trunk. Fingers may be joined together and many times a person has less than 5 fingers or toes in one or more hands or feet. Other symptoms that may or may not be observed are mental retardation, cleft palate, small jaw and hemangiomas, a type of arterial malformation which causes red marks, but is benign. Abnormalities concerning the internal organs may also be present.

Phocomelia can be detected during pregnancy, with the use of an ultrasound. This examination will prompt further evaluation. Upon childbirth, a simple physical examination will reveal deformities compatible with the condition. Treatment aims at surgically correcting some of the features that can be repaired and at lifestyle changes, so that a person can learn to function alternatively, without the full use of their limbs. Prosthetic devices have greatly evolved and myoelectric ones can interpret signals sent by the muscles and produce a natural movement. Children born with phocomelia should be encouraged to learn to adapt and be independent; patients have showed impressive ability to perform the very same tasks a healthy individual can, by personal adaptations and changes.

References

Article

  1. 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.
  2. Källén B, Rahmani TMZ, Winberg J. Infants with congenital limb reduction registered in the Swedish register of congenital malformations. Teratology. 1984; 29:73–85.
  3. Rosano A, Botto LD, Olney RS, Khoury MJ, Ritvanen A, Goujard J, Stoll C, Cocchi G, Merlob P, Mutchinick O, Cornel MC, Castilla EE, Martínez-Frías ML, Zampino G, Erickson JD, Mastroiacovo P. Limb defects associated with major congenital anomalies: Clinical and epidemiological study from the International Clearinghouse for Birth Defects Monitoring Systems. Am J Med Genet. 2000; 93:110–116.
  4. Evans JA, Vitez M, Czeizel AE. Congenital abnormalities associated with limb deficiency defects: A population study based on cases from the Hungarian Congenital Malformation Registry (1975–1984) Am J Med Genet. 1994; 49:52–66.
  5. Calzolari E, Maservigi GP, Garani GP, Cocchi G, Magnani C, Milan M. Limb reduction defects in Emilia Romagna, Italy: Epidemiologic and genetic study in 173,109 consecutive births.J Med Genet. 1990; 27:353–357.
  6. Sadler TW. Text book of Langman’s Medical Embryology. Skeletal system. 11th Ed. New Delhi [South Asian edition]: Wolters kluwer; 2010:140
  7. Schocnwolf GC, Bleyl SB, Brauer PR, Francis-West PH. Larsen’s Human Embryology. Development of limbs. 4thed. Phildelphia: John F. Kennedy; 2009:619.
  8. Olney R.S, Joyme H.E, Roche F, Ferguson K, Hintz S, Madan A. Limb/Pelvis Hypoplasia. Aplasia With Skill Defect (Schinzel Phocomelia) “Distinctive Features And Prenatat Detection". American Journal of Medicine.2001; 103 (4): 205–301
  9. Moore KL, Persaud TVN, Torchia MG. Textbook of essentials of embryology and birth defects. The musculoskeletal system. 7th Ed. Phildelphia: John F. Kennedy; 2008: 248
  10. Karabulut AB, Aydin H, Erer M, Mezdegi A, Guven E. Roberts syndrome from the plastic surgeon's viewpoint. Plast Reconstr Surg. 2001;108:1443–5 

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Last updated: 2017-08-09 17:53