Prenatal diagnosis of MIDAS/MLS syndrome associated with a deletion at Xp22.1

Abstract

Deletions of Xp22 have been associated with a phenotype involving micropthalmia, linear skin defects of the upper half of the body, and corneal opacities. This phenotype has been described under a variety of names including MIDAS syndrome (Microphthalmia, Dermal Aplasia, and Sclerocornea), MLS (Microphthalmia with Linear Skin defects) and Gazali-Temple syndrome. The condition has been reported exclusively in females, with the exception of at least two XX phenotypic males. The severity in females is variable. Mild cases may be characterized by short stature and minimal residual facial scarring. More severe cases can include the skin lesions and eye anomalies, as well as more severe anatomic defects such as agenesis or hypoplasia of the corpus callosum, congenital heart defects, genital anomalies, and rarely, diaphragmatic hernia. We describe the first prenatal diagnosis of this condition in the absence of a family history. An amniocentesis performed at 18 weeks gestational age due to sonographic detection of a diaphragmatic hernia revealed a karyotype of 46,X,del(X)(p22.1). Parental karyotypes were normal. Communication with the cytogenetics laboratory suggested that the phenotype of the fetus would most likely be similar to Turner syndrome, with an unrelated diaphragmatic hernia. Additional sonographic findings at 25 weeks included mild ventriculomegaly, polyhydramnios, and poor visualization of the cavum septum pellucidum, suggesting agenesis of the corpus callosum. Based on the cytogenetic and sonographic findings, a diagnosis of MIDAS/MLS syndrome was suspected. Autopsy performed following elective termination revealed a left diaphragmatic hernia, bilateral linear skin defects of the face and neck, and probable agenesis of the corpus callosum. Pathological evaluation of the eyes was not performed, although on gross evaluation the eyes were noted to be small. These post mortem findings are consistent with MIDAS/MLS syndrome. Prenatal detection of Xp22 deletions should prompt a detailed evaluation for features of MIDAS/MLS syndrome.