Abstract
Rizvi M, Lypka M, Kovacev T, Agris J. Median facial cleft dysmorphism in three siblings: case report and review of the literature. Cleft Palate Craniofac J. 2010;47:104–106. (PMID: 19860523).
We read with interest the recent report by Rizvi et al. (2010) describing three siblings with median facial clefts, including hypertelorbitism, broad nasal root, cleft of the nose, median cleft of the upper lip, and primary telecanthus. Although the authors suggested that this was associated with “probable” autosomal or X-linked dominant inheritance, the presence of affected siblings of both sexes, with unaffected parents, is much more suggestive of autosomal recessive inheritance.
In May 2009 we described a newly defined autosomal recessive syndrome, which we termed frontorhiny (OMIM 136760), characterized by a distinctive facial appearance with hypertelorism, wide nasal bridge, short nasal ridge, bifid nasal tip, broad columella, widely separated slit-like nares, long philtrum with prominent bilateral swellings, and midline notch in the upper lip and alveolus (Twigg et al., 2009). Homozygous loss-of-function mutations of ALX3, encoding the aristaless-related ALX homeobox 3 transcription factor, were identified in all seven families analyzed.
The facial features of the individuals illustrated in the report by Rizvi et al. (2010) bear a striking resemblance to those we observed in our series of patients with frontorhiny, and the pedigree of their family is consistent with autosomal recessive inheritance. We would like to suggest that molecular genetic testing of ALX3 is indicated in this family and that this would very likely reveal pathognomonic mutations in this gene.