Clinical Guidance

Individuals with ACTG2 visceral myopathy can experience functional defects of smooth muscle involving both bladder and bowel. Bladder involvement can range from neonatal megacystis and megaureter (with its most extreme form of prune belly syndrome) at the more severe end to recurrent urinary tract infections and bladder dysfunction at the milder end. Intestinal involvement can range from malrotation, neonatal manifestations of microcolon, and megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) to chronic intestinal pseudoobstruction (CIPO) in neonates, infants, children, and adults. The clinical severity can range within a family; mildly affected family members may not be aware of the diagnosis. For example: • One individual (in a multi-generation Finnish family) with an ACTG2 pathogenic variant reported episodic mild abdominal pain but no surgery and no signs of visceral myopathy at age 19 years . • One individual diagnosed with "spastic colon" and irritable bowel syndrome had not required surgery or intervention in middle age . Table 2. ACTG2 Visceral Myopathy: Frequency of Select Features Feature | Percentage

Source: GeneReviews — "ACTG2 Visceral Myopathy"

Clinical Guidance

Genotype-phenotype correlations have been identified for the following pathogenic variants (see also ): . Six of eight probands with missense variants at p.Arg40 had a favorable outcome.

p.Arg178

• All 17/17 probands with missense variants at p.Arg178 had a poor outcome . All were TPN dependent and at least one had undergone a multiorgan transplantation.

• Nineteen of 20 (95%) individuals with missense variants at p.Arg178 had microcolon .

. Sixteen of 26 (61.5%) probands with missense variants at p.Arg257 had a poor outcome. Five of 26 (19%) had microcolon; of these, three had a poor outcome and two a favorable outcome .

Source: GeneReviews — "ACTG2 Visceral Myopathy"

Penetrance

To date penetrance of ACTG2 visceral myopathy appears to be complete, as no family members heterozygous for a known ACTG2 pathogenic variant have been completely symptom free.

Source: GeneReviews — "ACTG2 Visceral Myopathy"

Differential Diagnosis

Approximately 62% (33/53) of individuals with a clinical diagnosis of visceral myopathy have a heterozygous pathogenic ACTG2 variant [. Other genes known to be associated with visceral myopathy are summarized in . Note: Because mydriasis has been identified in some individuals with MMIHS (megacystis-microcolon-intestinal hypoperistalsis syndrome) but not in those with ACTG2 visceral myopathy, the presence of mydriasis may suggest a different disorder. Table 3. Inherited Disorders with Gastrointestinal/Genitourinary Visceral Myopathy in the Differential Diagnosis for ACTG2 Visceral Myopathy

Source: GeneReviews — "ACTG2 Visceral Myopathy"

Clinical Guidance

Treatment/medications to be avoided or limited include those that diminish bowel and bladder motility. Opioids are known to decrease intestinal dysmotility and should be used with caution .

Source: GeneReviews — "ACTG2 Visceral Myopathy"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "ACTG2 Visceral Myopathy"