Ambiguous genitalia, microcephaly, seizures, bone malformations, and early death: A distinct MCA/MR syndrome

Abstract

We report on two siblings with hypotonia, ambiguous genitalia, microcephaly, ptosis, microretrognathia, thin lips, seizures, absent ossification of pubic rami, and brain abnormalities at the MRI. The two siblings died at 5 and 8 months, respectively. Molecular analysis indicated that SOX9, ARX, and DHCR7 genes were normal. Comparative genomic hybridization (CGH)-array analysis performed on the younger boy indicated two notable deletions, one on paternally inherited chromosome 4, and one on maternally inherited chromosome 5. The same deletions were found in a normal sister. Differential diagnoses and the possibility of a hitherto unreported syndrome are discussed.

Arx together with FoxA2, regulates Shh floor plate expression

“…Its expression is first detected at the 3 somite stage (~E8) in mouse embryos and it persists through early postnatal life (Colombo et al, 2004). Mutations ARX have been linked to morphological brain anomalies as well as multiple neurologic deficits in patients (Friocourt and Parnavelas, 2010; Kato et al, 2004; Kitamura et al, 2002; Mégarbané et al, 2011; Olivetti and Noebels, 2012; Sherr, 2003; Shoubridge et al, 2010; Strømme et al, 2002). Arx -deficient mice have intermediate progenitor cell proliferation defects in the forebrain resulting in small brains (Colasante et al, 2013; Kitamura et al, 2002).…”