Background: Holoprosencephaly (HPE) is a spectrum of midline malformations of the prosencephalon generally reflected in a continuum of midline facial anomalies. Patients with mutation in the ZIC2 gene usually present a normal or mildly dysmorphic face associated with a severe brain malformation. Here we present a rare unilateral nasal cleft (Tessier cleft n. 1) with holoprosencephaly in a patient with a ZIC2 mutation.
Case: The male newborn presented with alobar HPE, microcephaly, ocular hypertelorism, upslanting palpebral fissures, a bulky nose with a left paramedian alar cleft. Mutational screening for HPE genes revealed the occurrence of a frameshift mutation in the ZIC2 gene. The mutation was inherited from the father who presented only mild ocular hypotelorism but had an affected child with HPE from his first marriage.
Conclusion: The occurrence of oral clefts is common in patients with HPE, but unusual in patients with mutation in the ZIC2 gene. To our knowledge, clefts of the nasal alae have been reported only once or twice in patients with ZIC2 mutations. In documented patients from the literature, only 2% of individuals with described pathogenic mutations in the ZIC2 gene (3/171) presented facial clefts, one of them a nasal cleft, while common oral clefts were observed in 27% of individuals (7/26) described with nonpathogenic ZIC2 mutations or presenting a concomitant mutation in another HPE gene. When compared with the general population, nasal clefts are common in ZIC2 mutations and these mutations must be searched for in undiagnosed cases.
Keywords: Tessier number 1 cleft; ZIC2 mutations; alar cleft; atypical facial cleft; holoprosencephaly; nasal ala cleft.
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