Brachydactyly type E

Title

Other Names:

Type E brachydactyly

Categories:

Congenital and Genetic Diseases; Musculoskeletal Diseases

Summary Summary

Brachydactyly type E is a genetic disorder that causes some of the bones of the hands or feet to be shorter than expected. Other signs of the disorder may include having very flexible joints (hyperextensibility) in the hands and being shorter than family members who do not have the disorder (short stature).^[1]^[2] Brachydactyly type E can be isolated or syndromic. If the disorder is isolated, it means that the person does not have any other health problems or symptoms related to having brachydactyly type E. If brachydactyly type E is syndromic, it means a person has another genetic disease or health issue that includes the shortening of the hand and feet bones as one of its symptoms.^[3]^[4]

Isolated brachydactyly type E is caused by genetic changes (pathogenic variants or mutations) in the HOXD13 gene. Pathogenic variants in the the PTHLH gene may also cause brachydactyly type E associated with short height. In both of these cases, the disorder is inherited in an autosomal dominant manner. Other genetic changes are known to cause syndromes that include brachydactyly type E as a symptom. In these cases, the inheritance pattern depends on the underlying syndrome. Brachydactyly type E can be diagnosed if a doctor notices very flexible joints of the hands and shortening of the bones in the hands or feet. Genetic testing may be used to rule out genetic syndromes associated with brachydactyly.^[3]^[4] If brachydactyly type E is isolated and is not causing other physical or health problems, treatment may not be necessary.^[4]

Last updated: 4/22/2018

Symptoms Symptoms

Brachydactyly type E causes some of the bones of the hands or feet to be shorter than expected, which causes the hands and feet to appear small. Specifically, the bones that are shortened in people with brachydactyly type E are the metacarpals (bones in the hands) and metatarsals (bones in the feet). In some cases, the long bones of the fingers or toes (phalanges) may also be shortened. Other signs and symptoms of brachydactyly type E may include having very flexible joints in the hands (hyperextensibility), having a round face, and being shorter than expected (short stature). Depending on the genetic cause other symptoms may be present, including learning disabilities and problems with teeth.^[1]^[2]^[3]^[4]

The shortening of the bones in the hands and feet in people with brachydactyly type E may be noticed shortly after birth, however the difference often becomes more obvious as people get older.^[5] The number of metacarpals and metatarsals that are smaller than normal can range from a few of the bones to all of the bones, even within the same family. When the symptoms of a disorder vary even with the same genetic change, the disorder is said to have variable expressivity.^[1]

Last updated: 4/22/2018

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Short metacarpal	Shortened long bone of hand	0010049
Type E brachydactyly		0005863
30%-79% of people have these symptoms
Joint hyperflexibility	Joints move beyond expected range of motion	0005692
Short distal phalanx of finger	Short outermost finger bone	0009882
Short stature	Decreased body height Small stature [ more ]	0004322
5%-29% of people have these symptoms
Aplasia/Hypoplasia of the distal phalanx of the hallux	Absent/small outermost big toe bone Absent/underdeveloped outermost big toe bone [ more ]	0010076
Frontal bossing		0002007
Macrocephaly	Increased size of skull Large head Large head circumference [ more ]	0000256
Short metatarsal	Short long bone of foot	0010743
Upper limb asymmetry	Unequal size of arms	0100560
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance		0000006
Brachydactyly	Short fingers or toes	0001156
Moderately short stature	Moderate short stature	0008848
Multiple impacted teeth	Impacted teeth	0001571
Round face	Circular face Round facial appearance Round facial shape [ more ]	0000311
Short clavicles	Short collarbone	0000894
Straight clavicles	Straight collarbone	0006587

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 11/1/2019

Do you have updated information on this disease? We want to hear from you.

Cause Cause

Brachydactyly type E can be isolated or syndromic. Syndromic means there are other physical differences or health problems present due to the same genetic change. In these cases, there may be an underlying genetic syndrome that is causing the shortened hands and feet and other health problems.

When brachydactyly type E is isolated, meaning a person has shortened bones in the hands and feet but no other physical differences or related health problems, it may be caused by genetic changes (pathogenic variants or mutations) in HOXD13 gene. Pathogenic variants in the the PTHLH gene can also cause brachydactyly type E. Changes in this gene are also usually associated with short height and in some cases learning disabilities and problems with teeth.^[3]^[4]Both of these genes provide instructions for proteins that help control bone growth.^[6]^[7]

It is thought that there may be other genes in which pathogenic variants cause isolated brachydactyly type E with or without short stature. This is because some people with isolated brachydactyly type E with or without short stature do not have pathogenic variants in the PTHLH or HOXD13 genes.^[8]

Last updated: 4/22/2018

Inheritance Inheritance

When caused by pathogenic variants in the PTHLH or HOXD13 gene, brachydactyly type E is inherited in an autosomal dominant manner.^[1] Like most genes, the PTHLH or HOXD13 genes come in a pair (two copies of each gene). One copy of the genes is inherited from each parent. When a syndrome is inherited in an autosomal dominant manner, a person must have a pathogenic variant in only one copy of the gene to have the disorder. When a person with a pathogenic variants in either the PTHLH or HOXD13 gene has children, for each child there is a:

50% chance to inherit the change in the PTHLH or HOXD13 gene, meaning the child will have brachydactyly type E
50% chance to inherit the working copy of the PTHLH or HOXD13 gene, meaning the child will not have brachydactyly type E

If a person has brachydactyly type E and other related physical or health problems, the underlying genetic syndrome may be inherited in a different pattern.^[5]

Last updated: 4/22/2018

Diagnosis Diagnosis

Brachydactyly type E may be diagnosed when a doctor finds that a baby, child, or adult has shorter hands and feet than expected and also has very flexible (hyperextensible) joints in the hands. In some cases, a doctor may order x-rays of the hands and feet to confirm the diagnosis. A doctor may also take a thorough medical and family history and perform a physical exam and other tests to determine if there are any other health problems or physical differences that may be related to a genetic syndrome. In some cases, genetic testing may be used to confirm if the disorder is isolated or associated with another genetic syndrome.^[4]

Last updated: 4/22/2018

Prognosis Prognosis

Most people who only have brachydactyly type E without any other health or physical problems do not find their quality of life affected very much by having smaller hands and feet, as long as they have full use of their hands and feet. If brachydactyly type E is caused by an underlying genetic syndrome, the long-term outlook can vary depending on the underlying syndrome.^[5]^[9]

Last updated: 4/22/2018

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

The University of California San Francisco Limb Study is researching the genetic causes of limb malformations. They are looking for participants who only have problems with their limbs, such as fused or webbed fingers/toes, more than 5 fingers/toes, less than 5 fingers/toes, split hand and foot also called ectrodactyly, short fingers/toes, bent pinky fingers, extra long fingers, flexed fingers, club foot, etc. Visit the study’s website to learn more about who is eligible to take part in this study.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Brachydactyly type E. Click on the link to view a sample search on this topic.

Selected Full-Text Journal Articles

The Orphanet Journal of Rare Diseases has published an article with information on this condition. This journal is affiliated with the Orphanet reference portal for information on rare diseases and orphan drugs.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

Have a question? Contact a GARD Information Specialist.

References References

Brachydactyly type E. Orphanet. October 2010; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=93387.
Brachydactyly, Type E1; BDE1. Online Mendelian Inheritance in Man. June 21, 2016; https://www.omim.org/entry/113300.
Pereda A, Garin I, Spanish Network for Imprinting Disorders, and Perez de Nanclares G. What to consider when pseudohypoparathyroidism is ruled out: iPPSD and differential diagnosis. BMC Medical Genetics. 2018; 19:32. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834905/.
Page MM, Hooper AJ, Glendenning P, and Burnett JR. Isolated brachydactyly type E and idiopathic pancreatitis in a patient presenting to a lipid disorders clinic. BMJ Case Reports. April 6, 2017; https://www.ncbi.nlm.nih.gov/pubmed/28385908.
Pereda A, Garin I, Garcia-Barcina M, Gener B, Beristain E, Ibañez AM, and Perez de Nanclares G. Brachydactyly E: isolated or as a feature of a syndrome. Orphanet Journal of Rare Diseases. 2013; 8:141. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3848564/.
Flöttmann R, Sowinska-Seidler A, Lavie J, Chateil JF, Lacombe D, Mudlos S, Horn D, and Spielmann M. Duplication of PTHLH causes osteochondroplasia with a combined brachydactyly type E/A1 phenotype with disturbed bone maturation and rhizomelia. European Journal of Human Genetics. August 2016; 24(8):1132-1136. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/26733284/.
HOXD13 homeobox D13 [Homo sapiens (human)]. National Center for Biotechnology Information. April 8, 2018; https://www.ncbi.nlm.nih.gov/gene/3239.
Fontana P, Tortora C, Petillo R, Malacarne M, Cavani S, Miniero M, D’Ambrosio P, De Brasi D, and Pisanti M. Brachydactyly type E in an Italian family with 6p25 trisomy. European Journal of Medical Genetics. March 2017; 60(3):195-199. https://www.ncbi.nlm.nih.gov/pubmed/28111183.
Temtamy SA and Aglan MS. Brachydactyly. Orphanet J Rare Dis. 2008; 3:15. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2441618/.