Table II. MMIHS and MSMDS: Summary of Clinical Data and Genotype of Individuals With Molecularly Confirmed Diagnosis.

Phenotype	Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS)		Multisystemic smooth muscle dysfunction syndrome (MSMDS)
Gene	ACTG2a	MYH11b	ACTA2c
Number of probands	23	1	23
Parental consanguinity	−	+ (Algerian origin)	−
Inheritance	AD	AR	AD
Pathogenic variant	Heterozygous—all missense	Homozygous—stop codon	Heterozygous—all missense (codon 179)
De novo variant	16/18d	No	23/23
Familial recurrence of the phenotype	1/23e	−	−
Megacystis	21/23	+	4/23
Bladder dysfunction without	2/23	−	10/23
megacystis
Microcolon	16/23	+	−
Intestinal hypoperistalsis	21/21f	+	5/23
Prune-belly	2/20g	+	2/23
Mydriasis	−	−	23/23
Patent ductus arteriosus	−	−	23/23
Vascular involvement			23/23
Cerebrovascular	−	−	21/23
Aortic aneurism	−	−	14/23

AD, autosomal dominant, AR, autosomal recessive, MMIHS, megacystis-microcolon-intestinal hypoperistalsis syndrome; MSMDS, multisystemicsmooth muscle dysfunction syndrome; +, feature present; —, feature absent. A summary of phenotype, genotype, and family history data of all individuals with ACTG2-related disorder, including MMIHS and milder phenotypes, is described in the supplementary material (SM5).

^a[Thorson et al., 2014]; [Wangler et al., 2014]; [Tuzovic et al., 2015]; [Halim et al., 2016].

^b[Gauthier et al., 2014].

^c[Milewicz et al., 2010]; [Al-Mohaissen et al., 2012]; [Moller et al., 2012]; [Munot et al., 2012]; [Richer et al., 2012]; [Meuwissen et al., 2013]; [Moosa et al., 2013]; [Amans et al., 2014]; [Brodsky et al., 2014]; [Roulez et al., 2014]; [Yetman et al., 2015].

^dUnknown finding in five of the 23 individuals (18 evaluated patients), 16/18, one individual inherited the variant from the father, who presented with milder disease—family 34 [Wangler et al., 2014] and parental inheritance in a family due to probable gonadal mosacism—family 1 [Tuzovic et al., 2015].

^eThe recurrence of MMIHS was reported in a family with two affected siblings and normal parents—family 1 [Tuzovic et al., 2015].

^fUnknown finding in two of the 23 individuals (21 evaluated patients).

^gUnknown finding in three of the 23 individuals (20 evaluated patients).