Split hand/split foot malformation (SHFM) is a genetic disorder characterized by the complete or partial absence of some fingers or toes, often combined with clefts in the hands or feet. There may also be the appearance of webbing between fingers or toes (syndactyly). This may give the hands and/or feet a claw-like appearance.
There are many types and combinations of deformities that appear in split hand/split foot malformation. They range widely in severity, even in members of the same family. The malformation may occur alone, or it may occur as a component of a syndrome with other characteristics.
Typical cases of split-hand deformity usually appear in two forms. In the lobster claw variety there is usually an absence of the third digit. Located in the position of the third digit is a cone-shaped cleft that tapers in toward the wrist and divides the hand into two parts. The resulting deformed hand resembles a lobster claw. The remaining fingers or parts of fingers on each side of the cleft are often joined or webbed together. When a cleft occurs, it is usually present in both hands. A similar deformity commonly occurs in the feet.
In the second variety of split-hand deformity, there is the presence of only the fifth digit (monodactyly) and no cleft. There are varying levels of severity between these types, and cases of each type occasionally are found in the same family.
A form of SHFM associated with deafness has also been described.
Individuals with split-hand deformity usually have normal life spans and intelligence. Difficulties in physical functioning are related to the severity of the deformity.
Split-hand deformity is inherited as an autosomal dominant trait in some families and inherited as an X-linked recessive trait in other families. It may also occur as a result of a random (sporadic) mutation. When one limb is affected, the cause is often a new gene mutation, whereas when four limbs are affected, the cause is often an inherited gene mutation.
Five different abnormal genes have been found to be associated with non-syndromic SHFM. An abnormality in any one of these genes can lead to SHFM. SHFM1 has been mapped to chromosome 7, SHFM3 has been mapped to chromosome 10, SHFM4, caused by an abnormality in the TP63 gene, has been mapped to chromosome 3, SHFM5 has been mapped to chromosome 2 and SHFM2 has been mapped to the X chromosome.
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 7q21-22” refers to a location between bands 21 and 22 on the long arm of chromosome 7. 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.
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% for each pregnancy regardless of the sex of the resulting child. Occasionally, split hand/split foot malformation will skip a generation, and affected offspring will be born to unaffected parents.
X-linked recessive genetic disorders are conditions caused by an abnormal gene on the X chromosome. Females have two X chromosomes but one of the X chromosomes is “turned off” and all of the genes on that chromosome are inactivated. Females who have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is “turned off”. A male has one X chromosome and if he inherits an X chromosome that contains a disease gene, he will develop the disease. Males with X-linked disorders pass the disease gene to all of their daughters, who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease, and a 25% chance to have an unaffected son.
Split hand/split foot malformation affects males and females equally. Frequency is estimated at one out of 18,000 newborns.
The diagnosis of SHFM is based on physical features present at birth. X-rays may provide additional information about the skeletal anomalies. Molecular genetic testing by DNA analysis is available for SHFM4, caused by a mutation in the TP63 gene. Mutations in the TP63 gene are responsible for only about 10% of all cases of SHFM.
Reconstructive surgery can be performed on people with SHFM when applicable, and prosthetics are available to achieve normal functioning. Other treatment is symptomatic and supportive.
Genetic counseling may be of benefit for patients and their families.
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Sifakis S, Tsipouras P. Split Hand/Split Foot Malformation. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:256.
Royce PM, Steinmann B. Connective Tissue and Its Heritable Disorders. 2nd ed. Wiley-Liss, Inc., New York, NY. 2002:1002-04; 1014.
Berdon-Zapata V, Granillo-Alvarez M, Valdes-Flores M, et al. p63 gene analysis in Mexican patients with syndromic and non-syndromic ectrodactyly. J Orthop Res. 2004;22:1-5.
De Mollerat XJ, Gurrieri F, Morgan CT, et al. A genomic rearrangement resulting in a tandem duplication is associated with split hand-split foot malformation 3 (SHFM3) at 10q24. Hum Mol Genet. 2003;12:1959-71.
Duijf PH, van Bokhoven H, Brunner HG. Pathogenesis of split-hand/split-foot malformation. Hum Mol Genet. 2003;12 Spec No 1:R51-60.
Brunner HG, Hamel BC, Bokhoven Hv H. P63 gene mutations and human developmental syndromes. Am J Med Genet. 2002;112:284-90.
Brunner HG, Hamel BC, Van Bokhoven H. The P63 gene in EEC and other syndromes. J Med Genet. 2002;39:377-81.
Gul D, Oktenli C. Evidence for autosomal recessive inheritance of split hand/split foot malformation: a report of nine cases. Clin Dymorphol. 2002;11:183-86.
Safakis S, Basel D, Ianakiev P, et al. Distal limb malformations: underlying mechanisms and clinical associations. Clin Genet. 2001;60:165-72.
Witters I, Van Bokhoven H, Goossens A, et al. Split-hand/split-foot malformation with paternal mutation in the p63 gene. Prenat Diagn. 2001;21:1119-22.
Grimm T, Teglund S, Tackels D, et al. genomic organization and embryonic expression of
Van Bokhoven H, Hamel BC, Bamshad M, et al. p63 Gene mutations in eec syndrome, limb-mammary syndrome, and isolated split hand-split footmalformation suggests a genotype-phenotype correlation. Am J Hum Genet. 2001;69:481-92.
Haak MC, Cobben JM, van Vugt JM. First semester diagnosis split hand/foot by transvaginal ultrasound. Fetal Diagn Ther. 2001;16:146-49
Tackels-Horne D, Toburen A, Sangiorgi E, et al. Split hand/split foot malformation with hearing loss: firast report of families linked to the SHFM1 locus in 7q21. Clin Genet. 2001;59:28-36.
FROM THE INTERNET
Albuisson J. Split hand split foot. Orphanet. January 2004. 1pp.
McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University.
Split-Hand/Foot Malformation 1; SHFM1. Entry Number; 183600: Last Edit Date; 3/19/2004.
Split-Hand/Foot Malformation 2; SHFM2. Entry Number; 313350: Last Edit Date; 3/18/2004.
Split-Hand/Foot Malformation 3; SHFM3. Entry Number; 600095: Last Edit Date; 11/6/2003
Split-Hand/Foot Malformation 4; SHFM1. Entry Number; 605289: Last Edit Date; 2/21/2002
Split-Hand/Foot Malformation 5; Entry Number; 606708: Last Edit Date; 3/19/2004
Lobster hand. ©2004. 2pp.
Everman DB. Split Hand/Split Foot Malformation. Molecular Investigation of Human Split-Hand Malformation (SHFM). Greenwood Genetic Center. nd. 2pp.
Thami GP, Kaur S. Split hand-foot malformation: a congenital central limb ray deficiency. JPGM. 2002;48:209-10.