Rare Hematology News

Disease Profile

Brachydactyly type E

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Antenatal

ICD-10

Q73.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

rnn-autosomaldominant.svg

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

no.svg

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

no.svg

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

no.svg

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

no.svg

Other names (AKA)

Type E brachydactyly

Categories

Congenital and Genetic Diseases; Musculoskeletal Diseases

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]

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] 

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.

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

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]

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]

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.

References

  1. Brachydactyly type E. Orphanet. October 2010; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=93387.
  2. Brachydactyly, Type E1; BDE1. Online Mendelian Inheritance in Man. June 21, 2016; https://www.omim.org/entry/113300.
  3. 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/.
  4. 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.
  5. 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/.
  6. 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/.
  7. HOXD13 homeobox D13 [Homo sapiens (human)]. National Center for Biotechnology Information. April 8, 2018; https://www.ncbi.nlm.nih.gov/gene/3239.
  8. 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.
  9. Temtamy SA and Aglan MS. Brachydactyly. Orphanet J Rare Dis. 2008; 3:15. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2441618/.

Rare Hematology News