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

• Visceral Myopathy due to ACTG2 Gene Mutation

What are ACTG2-Related Disorders? (Definition/Background Information)

• ACTG2-Related Disorders are a subset of visceral myopathy (a condition where the intestine is unable to push food through, but where there is not a real intestinal obstruction) with variable involvement of the bladder and intestine
• ACTG2-Related Disorders are caused by alterations (mutations) of the ACTG2 gene and is inherited in an autosomal dominant manner  
• It includes three different conditions:
  • Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS)
  • Prune belly sequence or syndrome
  • Chronic intestinal pseudo-obstruction (CIPO)
• Bladder involvement can range from neonatal megacystis (a bladder with increased size) and megaureter(ureter abnormally wide) at the more severe end, to recurrent urinary tract infections and bladder dysfunction at the milder end
• Affected infants (with or without evidence of intestinal malrotation) often present with feeding intolerance and findings of non-mechanical bowel obstruction that persist after successful surgical correction of malrotation. 
• Individuals, who develop manifestations of CIPO in later childhood or adulthood, often have episodic waxing and waning of bowel motility. They may need frequent abdominal surgeries (perhaps related to  intestinal malrotation or adhesions causing mechanical obstruction) resulting in resection of dilated segments of bowel, often becoming dependent on total parenteral nutrition

(Source: ACTG2-Related Disorders; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

Who gets ACTG2-Related Disorders? (Age and Sex Distribution)

• ACTG2-Related Disorders is a rare congenital disorder. The presentation of symptoms may occur at birth or in infancy
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for ACTG2-Related Disorders? (Predisposing Factors)

• A positive family history may be an important risk factor, since ACTG2-Related Disorders can be inherited
• Currently, no other risk factors have been clearly identified for these disorders

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 ACTG2-Related Disorders? (Etiology)

• ACTG2-Related Disorders are caused by mutation(s) in the ATCG2 gene that are inherited in an autosomal dominant manner

Autosomal dominant: 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.

What are the Signs and Symptoms of ACTG2-Related Disorders?

The signs and symptoms of ACTG2-Related Disorders may vary in type and severity, and include the following:

Signs and symptoms in the neonatal phase:

• Enlarged bladder
• Abnormally-wide ureter
• Abnormal bladder function
• Recurrent urinary tract infections

Signs and symptoms in infancy:

• Intestinal malrotation
• Feeding intolerance 
• Non-mechanical bowel obstruction that may persist even after surgery to correct intestinal malrotation

Signs and symptoms in older children and adults may include episodic waxing and waning of bowel motility.

(Source: ACTG2-Related Disorders; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

How are ACTG2-Related Disorders Diagnosed?

ACTG2-Related Disorders is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

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 ACTG2-Related Disorders?

The complications of ACTG2-Related Disorders may include:

• Chronic bladder dysfunction
• Malnutrition
• Inadequate weight gain
• Necessity for multiple surgeries
• Dependence on parenteral nutrition

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

How are ACTG2-Related Disorders Treated?

• There is no cure for ACTG2-Related Disorders, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops
• Abdominal surgeries to correct intestinal malrotation or adhesions may be necessary 

How can ACTG2-Related Disorders be Prevented?

ACTG2-Related Disorders may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• 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 ACTG2-Related Disorders? (Outcomes/Resolutions)

• The prognosis of ACTG2-Related Disorders 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 ACTG2-Related Disorders:

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

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