Phocomelia syndrome (PS) is a rare birth defect that causes severe birth defects, especially of the upper limbs. The bones of the arms, and in some cases other appendages, may be extremely shortened and even absent. The fingers of the hands may be fused. An extreme case results in the absence of the upper bones of both the arms and legs so that the hands and feet appear attached directly to the body. This is called tetraphocomelia.
This disorder, PS, may be genetically transmitted within families as an autosomal recessive trait or may be the result of spontaneous (sporadic) changes in the gene. Because the signs of the disorder so closely mimic those caused by the ingestion of thalidomide by pregnant women, the term "pseudo-thalidomide" is frequently used.
The primary symptom of phocomelia syndrome is deficient limb development. However, the defects of the limbs are variable. Commonly, the upper limbs are affected and sections of the hands and arms may be malformed or missing. The legs and the feet may also be affected. The hands and/or the feet may be attached close to the body or the limbs may be abnormally small.
Individuals with phocomelia syndrome usually have growth deficiencies before and after birth. In some cases, they also may be mentally retarded. The head may be small with sparse hair that may be silvery-blond. A swelling or mass of blood vessels (hemangioma) may occur on the face. Prominent widely set eyes (hypertelorism) that have bluish whites, an underdeveloped nose with thin nostrils, malformed ears, cleft lip with or without cleft palate, and small jaws (micrognathia) may also occur. The testes of males may fail to descend (cryptorchidism).
Less common symptoms include: a gap in the skull with the brain possibly protruding (encephalocele); accumulation of excess spinal fluid under the skull (hydrocephalus) which may cause headaches, vomiting, and convulsions, and small eyeballs (microphthalmia), corneal clouding, cataracts, and eyelid defects. The urethra (the tube leading from the bladder) may open underneath the penis or in females may open into the vagina (hypospadias). An abnormally shaped uterus (bicornate), an abnormally low level of platelets in the blood (thrombocytopenia), kidney and heart abnormalities, a short neck, and cranial nerve paralysis may also occur.
Disorder Subdivisions: If phocomelia is the result of drugs or pharmaceuticals, it is usually thought of as the thalidomide syndrome. This type of phocomelia is also characterized by severe and similar defects that are caused by the ingestion of the drug thalidomide (a tranquilizer) during early pregnancy. Thalidomide was widely used outside the United States in the late 1950’s and early 1960’s. The class of drugs used to treat acne, including Accutane, may also cause the skeletal malformations and other symptoms associated with phocomelia.
Phocomelia, in its familial heritable form, is transmitted as an autosomal recessive trait. The gene change (mutation) has been tracked to a site on chromosome 8 at gene map locus 8p21.1.
Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 8p21.1″ refers to band 21.1 on the short arm of chromosome 8. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.
Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25 percent with each pregnancy. The risk to have a child who is a carrier like the parents is 50 percent with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25 percent. The risk is the same for males and females.
All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.
Phocomelia syndrome may also occur as a result of the ingestion of certain drugs during pregnancy or for other unknown reasons. The drug thalidomide caused an unusual surge of babies born with severe birth defects during the 1960s, and the drug accutane (for treatment of acne) can also cause severe birth defects of this type.
The hereditary form of phocomelia is a very rare disorder affecting only a dozen or more babies born each year. Males and females seem to be affected in equal numbers but the sample size is too small to be certain. An upsurge of the number of phocomelia cases can signal that certain drugs are causing this birth defect. Thalidomide (a tranquilizer) and accutane (for treatment of acne) can cause phocomelia in a fetus when ingested by a pregnant woman.
Prenatal diagnosis is usually made as a result of ultrasound studies of the fetus. Although not absolute, ultrasound studies are usually reliable enough to suggest that further work is necessary. After the child is born, diagnosis becomes a matter of physical examination. As yet, there are no definitively accurate prenatal tests.
Treatment and rehabilitation of the limb deformities of phocomelia syndrome should be planned in infancy. Individual prostheses (artificial limbs) and orthopedic braces or appliances (ortheses) may be needed. Genetic counseling may be of benefit for patients and their families if the child has the genetic form of this disorder. Other treatment is symptomatic and supportive.
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RECENT JOURNAL ARTICLES
Schule B, Oviedo A, Johnston K, Pai S, Pasquina PF. Inactivating mutations in ESCO2 cause SC phocomelia and Roberts syndrome: no phenotype-genotype correlation. Am J Hum Genet. 2005;77:1117-28.
Pinette MG, Hand M, Hunt RC, Blackstone J, Wax JR, Cartin A. Surviving sirenomelia. J Ultrasound Med. 2005;24:1555-59.
Vega H, Waisfisz Q, Gordillo M, et al. Roberts syndrome is caused by mutations in ESCO2, a human homolog of yeast ECO1 that is essential for the establishment of sister chromatid adhesion. Nat Genet. 2005;37:468-70.
Gibbs PJ, Friend PJ, Darby CR. Renal replacement therapy in a patient with phocomelia. J R Soc Med. 2003;96:558.
Kozin SH. Upper-extremity congenital anomalies. J Bone Joint Surg Am. 2003;85-A(8):1564-76.
Tytherleigh-Strong G, Hooper G. The classification of phocomelia. J Hand Surg [BR], 2003;28:215-17.
FROM THE INTERNET
McKusick VA, Ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. SC Phocomelia Syndrome. Entry Number;269000: Last Edit Date;12/28/2005.
McKusick VA, Ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Roberts Syndrome; RBS. Entry Number; 268300: Last Edit Date;3/15/2006.