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

Abstract

The generic term median facial dysplasia (MFD) describes a subgroup of patients with cleft lip and palate exhibiting characteristic craniofacial defects: (1) short prolabium, (2) absence of frenulum labii, (3) hypoplasia of premaxilla, (4) absent upper central and lateral incisors of the cleft side, and (5) deficient septal cartilage and nasal spine. Gross brain malformations are usually absent in MFD. The same craniofacial malformations are also described in patients with holoprosencephaly sequence (HPE-S). We report on two male patients with bilateral cleft lip and palate showing the facial findings of MFD or HPE-S. Additional congenital malformations were anal atresia in one patient and severe cardiac defect in the other. In both, HPE was excluded by brain imaging, although uncommon brain anomalies were detected consisting of multiple white-matter lesions in the one patient and unusual enlargement and tortuosity of intracerebral blood vessels in both patients. In addition to facial anomalies, the patients also had psychiatric problems typically seen in velo-cardio-facial syndrome (VCFS). Fluorescence in situ hybridization (FISH) analysis confirmed a 22q11.2 microdeletion in both.

Prenatal diagnosis of trisomy 4p: a new locus for holoprosencephaly?

“…There may be a cryptic subcentromeric deletion in 22q due to an unbalanced translocation. Interestingly, 22q11.2 microdeletion has previously been reported in HPE probands (Schulze et al, 2001). However, in our case, we found no microdeletion in the 22q11.2 region with the used probe.…”

Prenatal diagnosis of frontonasal dysplasia with anterior encephalocele

“…Genetic aspects of frontonasal dysplasia are not well-defined. Although frontonasal dysplasia occurs sporadically in most of the cases, autosomal dominant and X-linked patterns, as well as 22q11 microdeletion have been reported in the literature (1,10,11). In general, the possibility of this syndrome occurring in the next sibling is suggested to be 25% (12).…”

Prenatal ultrasound diagnosis of frontonasal dysplasia

“…FND occurs sporadically (DeMeyer, 1967;Sedano et al, 1970;Guinon-Almeida et al, 1996), but some familial cases have been reported. Recently, autosomal dominant (Fryburg et al, 1993;Qureshi and Naeem-uz-Zfar, 1996;Nevin et al, 1999) and X-linked dominant inheritance (Fryburg et al, 1993;Nevin et al, 1999) have been suggested in some families, while 22q11 microdeletions have been detected in a few patients (Schultze et al, 2001).…”

“…A normal male karyotype was found at amniocentesis. FISH analysis for the detection of 22q11 microdeletion was not performed (Schultze et al, 2001). After prenatal counseling, the couple opted for termination of pregnancy and a pathological examination was performed.…”