Brachydactyly
Brachydactyly is a congenital condition characterized by the shortening of fingers or toes, often stemming from the underdevelopment or absence of segments known as phalanges. This condition can also involve other bones in the hands or feet. Inheritance plays a significant role in brachydactyly, with several genetic mutations identified as risk factors, alongside potential embryonic disturbances from external factors like teratogens during fetal development. Various forms of brachydactyly exhibit complex genetic patterns, including autosomal dominant, recessive, and incomplete inheritance, and are classified into types A through E, with subtypes that specify different digit abnormalities.
Symptoms may range from isolated digit shortening to more complex syndromic forms that can include additional skeletal and systemic issues. Diagnosis typically involves family history and may include prenatal ultrasound and genetic testing if a familial mutation is known. Treatment options are limited, focusing mainly on enhancing hand function through therapy or surgery when necessary. While isolated brachydactyly generally has a favorable prognosis, outcomes for syndromic forms depend on the severity of associated conditions. Overall, understanding brachydactyly requires awareness of its genetic complexities and variable presentations.
Brachydactyly
ALSO KNOWN AS: Brachymesophalangy; brachyphalangy; hypophalangia
DEFINITION Brachydactyly describes both a morphologic feature and a group of congenital hand deformities characterized by short fingers. In most cases, the reduced finger length is attributed to an underdevelopment or absence of finger segments called phalanges, although shortening of other bones of the hands or feet (metacarpals or metatarsals) may also occur.
Risk Factors
The greatest risk factor for the development of brachydactyly is the inheritance of one of several disease-causing mutations. Brachydactyly can also result from embryologic disturbances and has been observed among infants exposed to drugs known to alter fetal development (teratogens); in this case, it is usually found in conjunction with other malformations.
Etiology and Genetics
Although brachydactyly was the first human trait to be ascribed an autosomal dominant Mendelian inheritance pattern, it has subsequently proven to be a genetic smorgasbord, demonstrating the concepts of incomplete (wherein carriers of causative mutations do not show evidence of disease), variable (differences in clinical presentation among individuals with the same mutation), and locus heterogeneity (multiple genes or gene combinations leading to the same phenotype). In addition, evidence suggests that certain forms of brachydactyly may be inherited as semidominant or autosomal recessive traits.
Brachydactyly can be inherited alone (isolated brachydactyly), in association with skeletal abnormalities, or as part of a syndrome. In 1951, Julia Bell developed a classification scheme for isolated brachydactyly based on the characteristic hand malformations found in family pedigrees. Categorization of brachydactyly still follows this general model of types A through E, with subtypes used to further delineate particular patterns of digit abnormalities. The majority of isolated brachydactyly types are very rare, occurring in fewer than 200,000 people; however, brachydactyly types A3 and D are the most common, occurring in 2 percent of the population.
Causative mutations have been identified for many, but not all, of the isolated brachydactyly types. Mutations in the Indian hedgehog (IHH) gene (2q35-q36) have been identified in families with brachydactyly type A1, although linkage has also been shown to a locus on 5p13.3-p13.2. Mutations in two separate genes have been associated with brachydactyly type A2: the bone morphogenetic protein receptor 1B (BMPR1B) gene (4q21-q20) and the growth and differentiation factor 5 (GDF5) gene (20q11.2). This divergence among families with a common exemplifies the genetic heterogeneity within brachydactyly.
The phenotype of patients with brachydactyly type B has been shown to correlate with the nature of the mutation in the receptor kinase-like orphan receptor 2 (ROR2) gene (9q22). Mutations in ROR2 have also been identified in patients with autosomal recessive Robinow syndrome. More recently, mutations in the noggin (NOG) gene (17q22) have been identified in patients with brachydactyly type B for whom ROR2 mutations were not detected.
The inheritance pattern of brachydactyly type C is not straightforward and has been suggested to be autosomal dominant, autosomal recessive, or semidominant. As observed for brachydactyly type A2, mutations in GDF5 have been identified in families with brachydactyly type C.
Both brachydactyly types D and E have been linked to mutations in the homeobox-containing (HOXD13) gene (2q31-q32).
Symptoms
Isolated brachydactyly is characterized by shortening of one or more digits and may affect the hands, feet, or both. Other finger abnormalities, including syndactyly (fused digits), clinodactyly (sideways deviation of the finger), or symphalangism (fused phalanges), may also be present. Syndromic forms of brachydactyly may be associated with skeletal defects (such as short stature, shortened limbs, and scoliosis), hypertension, cardiac malformations, intellectual disability, or a host of other abnormalities.
Screening and Diagnosis
Family history is a strong predictor of disease. The benign nature of isolated brachydactyly makes prenatal screening unnecessary, although it may be valuable for syndromic forms of the disease. Prenatal ultrasound performed from twelve to seventeen weeks of gestation has been used to successfully diagnose brachydactyly. Diagnosis based on analysis of DNA from the fetus is possible if the familial mutation is known.
Treatment and Therapy
Plastic surgery is an option to enhance hand function but is not applicable in most cases. If needed, hand function may also be improved through physical therapy. For those with syndromic brachydactyly, treatment of associated conditions (such as blood pressure medication for patients with hypertension) may be indicated.
Prevention and Outcomes
There is no method available for preventing brachydactyly occurrence among individuals who inherit disease-causing mutations. The prognosis for patients with isolated brachydactyly is generally favorable; the ability to achieve normal hand function is reliant on the extent and severity of the defect. In cases of syndromic brachydactyly, prognosis is influenced by the nature of the associated conditions.
Bibliography
"Brachydactyly." Cleveland Clinic, 30 Aug. 2022, my.clevelandclinic.org/health/diseases/24081-brachydactyly. Accessed 9 Sept. 2024.
"Brachydactyly (Short Fingers or Short Toes)." Johns Hopkins Medicine, 2024, www.hopkinsmedicine.org/health/conditions-and-diseases/hand-conditions/congenital-hand-differences/brachydactyly-short-fingers-or-short-toes. Accessed 9 Sept. 2024.
Everman, David B. “Hands and Feet.” Human Malformations and Related Anomalies. Ed. Roger E. Stevenson and Judith G. Hall. 2nd ed. Oxford: Oxford UP, 2006. Print.
Firth, Helen V., Jane A. Hurst, and Judith G. Hall, eds. Oxford Desk Reference: Clinical Genetics. Oxford : Oxford UP, 2005. Print.
Glorieux, Francis H., John M. Pettifor and Harald Jüppner. Pediatric Bone: Biology and Diseases.2nd ed. London: Academic P/ Elsevier, 2012. Print.
Pereda, Arrate, Intza Garin, Maria Garcis-Barcina, Blanca Gener, Elena Beristain, Ane Miren Ibañez, and Guiomar Perez de Nanclares. "Brachydactyly E: Isolated or as a Feature of a Syndrome." Orphanet Journal of Rare Diseases 8 (2013): 141. Print.
Temtamy, Samia A., and Mona S. Aglan. “Brachydactyly.” Orphanet Journal of Rare Diseases 3 (2008): 15. Print.