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). 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.

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. If brachydactyly type E is isolated and is not causing other physical or health problems, treatment may not be necessary.

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. 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.

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 genecan 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.Both of these genes provide instructions for proteins that help control bone growth.

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.

PTHLH or HOXD13 gene, brachydactyly type E is inherited in an autosomal dominant manner. Like most genes, the PTHLH or HOXD13genes 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.

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.

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.