What are the other Names for this Condition? (Also known as/Synonyms)

• Familial Hirschsprung's Disease and Type D Brachydactyly

What is Hirschsprung Disease Type D Brachydactyly? (Definition/Background Information)

• Hirschsprung Disease Type D Brachydactyly is characterized by Hirschsprung disease and absence or hypoplasia of the nails and distal phalanges of the thumbs and great toes (type D brachydactyly)
• It has been described in four males from one family (two brothers and two maternal uncles)
• Transmission appears to be X-linked recessive but autosomal dominant inheritance with incomplete penetrance in females cannot be ruled out

(Source: Hirschsprung Disease Type D Brachydactyly; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Who gets Hirschsprung Disease Type D Brachydactyly? (Age and Sex Distribution)

• Hirschsprung Disease Type D Brachydactyly is an extremely rare congenital disorder, with only 4 cases being reported so far (in one particular family)
• The presentation of symptoms may occur at birth
• The reported cases are all males. It is not clear if females get affected
• The geographical distribution of this disorder is not known, owing to the limited number of reported cases

What are the Risk Factors for Hirschsprung Disease Type D Brachydactyly? (Predisposing Factors)

• A positive family history may be an important risk factor, since Hirschsprung Disease Type D Brachydactyly can be inherited
• The male gender may be a risk factor, based on the individuals currently affected

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Hirschsprung Disease Type D Brachydactyly? (Etiology)

• The gene mutation that causes Hirschsprung Disease Type D Brachydactyly is not presently known
• However, based on the fact that only males are affected in the affected family, it is possible that the condition may be transmitted in an X-linked recessive manner
• Alternatively, autosomal dominant inheritance with incomplete penetrance in women has been suggested by some researchers

X-linked recessive pattern of inheritance: The gene associated with this condition may be located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons

Autosomal dominant inheritance: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

Autosomal dominant inheritance with reduced or incomplete penetrance: Not everyone who inherits the faulty gene develops the condition, indicating that other genetic and environmental factors may play a role in the development of the disease.

What are the Signs and Symptoms of Hirschsprung Disease Type D Brachydactyly?

The signs and symptoms of Hirschsprung Disease Type D Brachydactyly may include:

• Aganglionic megacolon
• Short thumb
• Type D brachydactyly

(Source: Hirschsprung Disease Type D Brachydactyly; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

The most common symptom associated with Hirschsprung Disease is severe constipation. This may sometimes lead to a complete obstruction of the intestines. Other signs and symptoms include:

• Abdominal pain, swelling or bloating
• Vomiting and diarrhea
• Malnutrition
• Slowed growth and poor feeding

How is Hirschsprung Disease Type D Brachydactyly Diagnosed?

Hirschsprung Disease Type D Brachydactyly is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Radiographic studies (of abdomen)
• Rectal biopsy: The biopsy is examined under the microscope by a pathologist, to arrive at a definitive diagnosis. The rectal biopsy will show an absence of ganglion nerve cells
• Barium enema of intestine
• Anal manometry to measure the rectal pressure

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Hirschsprung Disease Type D Brachydactyly?

The complications of Hirschsprung Disease Type D Brachydactyly may include:

• Severe abdominal inflammation with frequent (smelly) diarrhea, which may take place before any treatment measures are advocated
• Intestinal rupture
• Short bowel syndrome
• Development of enterocolitis, after a surgical rectification of the condition
• Difficulty with normal functioning of hands, performing simple tasks, etc.

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Hirschsprung Disease Type D Brachydactyly Treated?

There is no cure for Hirschsprung Disease Type D Brachydactyly, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops.

The treatment measures for Hirschsprung Disease include:

• To reduce pressure in the bowel, serial rectal irrigation procedure is employed
• Surgical removal of the defective part of the colon (called colectomy), and reattachment of the functional part of the colon with the rectum. The surgery is performed in a single step or in multiple steps
• To help and regulate the intestinal function, a high-fiber diet with increased fluid intake is recommended
• In order to avoid constipation, prescribed laxatives may be used

The treatment for Brachydactyly may involve the following measures:

• Surgical correction of physical deformities
• Physiotherapy: To help improve the muscle tone via suitable exercises and heat therapy
• Ergotherapy: Use of recreation and work to improve functionality of the hands and feet

How can Hirschsprung Disease Type D Brachydactyly be Prevented?

Currently, Hirschsprung Disease Type D Brachydactyly may not be preventable, since it is a genetic disorder.

• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Hirschsprung Disease Type D Brachydactyly? (Outcomes/Resolutions)

• The prognosis of Hirschsprung Disease Type D Brachydactyly is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Hirschsprung Disease Type D Brachydactyly:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/