Meacham Syndrome

A number sign (#) is used with this entry because some patients with Meacham syndrome have mutations in the WT1 gene (607102).

See also Denys-Drash syndrome (194080), an allelic disorder with overlapping clinical features.

Clinical Features

Meacham et al. (1991) reported 2 unrelated genetic males with a novel constellation of genital, cardiac, and pulmonary malformations. The genital abnormalities consisted of a true double vagina, retention of mullerian structures, and undervirilization of the external genitalia. Both infants had complex cyanotic congenital heart defects, hypoplastic right lungs, anomalous pulmonary venous return, and abnormalities of the diaphragm. One patient had rhabdomyomatous dysplasia of the lungs. There was no family history of similar defects, no consanguinity, no known exposure to teratogens, and no chromosome abnormality. The authors suggested that the unusual occurrence of a true double vagina should lead to careful pulmonary and cardiac evaluation.

Toriello and Higgins (1991) reported another child with sex reversal and cardiac, pulmonary, and diaphragm defects.

Killeen et al. (2002) reported a female infant of 42 weeks' gestation with a left-sided diaphragmatic hernia and a hypoplastic left heart. A true double vagina, absent uterus, and abnormal male gonads were found in the presence of normal external female genitalia. Conventional G-band karyotyping of skin samples revealed a normal male karyotype. The authors stated that this was the fifth reported case of Meacham syndrome.

Suri et al. (2007) reported detailed clinical features of 8 patients, including 2 half-sibs, with Meacham syndrome. All had a normal male karyotype, 46,XY, with complex sex reversal or ambiguous genitalia, and congenital diaphragmatic hernia. Other symptoms, including heart, pulmonary, and genital defects, were variable. All patients died early in life. None had renal mesangial sclerosis or Wilms tumor, thus excluding a diagnosis of Denys-Drash syndrome.

Molecular Genetics

In 2 patients with Meacham syndrome, Suri et al. (2007) identified heterozygous mutations in the WT1 gene (R366W, 607102.0026 and R394W, 607102.0003); neither patient had congenital heart defects. DNA material from 6 other patients with this disorder was not available for testing. Suri et al. (2007) noted that both WT1 mutations had been identified in patients with Denys-Drash syndrome, illustrating the phenotypic overlap between the 2 disorders.