Misclassification risk of patients with bilateral cleft lip and palate andmanifestations of median facial dysplasia: A new variant of del(22q11.2) syndrome?

The generic term median facial dysplasia (MFD) describes a subgroup of pati ents with cleft lip and palate exhibiting characteristic craniofacial defec ts: (1) short prolabium, (2) absence of frenulum labii, (3) hypoplasia of p remaxilla, (4) absent upper central and lateral incisors of the cleft side, and (5) deficient septal cartilage and nasal spine. Gross brain malformati ons are usually absent in MFD. The same craniofacial malformations are also described in patients with holoprosencephaly sequence (HPE-S). We report o n two male patients with bilateral cleft lip and palate showing the facial findings of MFD or HPE-S. Additional congenital malformations were anal atr esia in one patient and severe cardiac defect in the other, In both, HPE wa s excluded by brain imaging, although uncommon brain anomalies were detecte d consisting of multiple white-matter lesions in the one patient and unusua l enlargement and tortuosity of intracerebral blood vessels in both patient s. In addition to facial anomalies, the patients also had psychiatric probl ems typically seen in velo-cardio-facial syndrome (VCFS). Fluorescence in s itu hybridization (FISH) analysis confirmed a 22q11.2 microdeletion in both . (C) 2001 Wiley-Liss, Inc.