Acrofacial dysostoses: Review and report of a previously undescribed condition: The autosomal or X‐linked dominant catania form of acrofacial dysostosis

Abstract

The acrofacial dysostoses (AFDs) are a heterogeneous group of disorders combining defects of craniofacial and limb development. The predominantly preaxial form is called Nager AFD, the predominantly postaxial form of AFD (POADS) is also known as the Genée-Wiedemann or Miller syndrome. The former appears to be about twice as common as the latter with well-documented autosomal dominant and recessive occurrences in both conditions. Only 1 AD occurrence of POADS is known, but 5 sets of sibs are suggestive of AR inheritance. Heterogeneity of apparently nonsyndromal AFD of both types is powerful support for the hypothesis that the AFDs are polytopic field defects arising during blastogenesis. Six other previously described forms of AFD include the AFD syndrome of Kelly et al. (AR), the Rodríguez or Madrid form of AFD (AR or XLR), the Reynolds or Idaho form of AFD (AD), the Arens or Tel Aviv type of AFD (AF?), the presumed AR AFD syndrome of Richieri-Costa et al., and the AD Patterson-Stevenson-Fontaine syndrome. Here we review the AFDs and report on a previously apparently undescribed autosomal or X-linked dominant form of AFD with mental retardation in a Sicilian mother and her 4 sons.

Acrofacial dysostosis (AFD) with preaxial limb hypoplasia (Nager AFD) and club foot diagnosed in a fetus from 1812 in the anatomical collections at the University of Halle, Germany

“…The AFDs are a heterogeneous group of disorders comprising defects of craniofacial and limb development [Opitz et al, 1993;Witkowski et al, 1995]. Preaxial upper limb defects point to the AFD Nager phenotype, whereas postaxial limb defects point to the Genée-Wiedemann or Miller syndrome [Opitz et al, 1993[Opitz et al, , 1998].…”

“…Preaxial upper limb defects point to the AFD Nager phenotype, whereas postaxial limb defects point to the Genée-Wiedemann or Miller syndrome [Opitz et al, 1993[Opitz et al, , 1998]. Diagnostically relevant are also Treacher CollinsFranceschetti syndrome, Robin sequence, and Stickler syndrome [Opitz et al, 1993;Witkowski et al, 1995;Hunt and Hobar, 2002]. The diagnosis should be based on the type of limb malformations [Witkowski et al, 1995].…”

“…The severity of the NAFD varies extremely between affected individuals, ranging from severe malformations and intruterine death to very mild forms, which may easily escape correct diagnosis [Opitz et al, 1993;David et al, 1996;Fryns et al, 1996;Hunt and Hobar, 2002]. The main facial characteristics for the pathological-anatomical diagnosis are mandibular hypoplasia, velar hypoplasia, and zygomatic bone hypoplasia [Opitz et al, 1993[Opitz et al, , 1998Hunt and Hobar, 2002].…”

“…The main facial characteristics for the pathological-anatomical diagnosis are mandibular hypoplasia, velar hypoplasia, and zygomatic bone hypoplasia [Opitz et al, 1993[Opitz et al, , 1998Hunt and Hobar, 2002]. Antimongoloid palpebral fissures and eyelash dysgenesis can almost always be found [Opitz et al, 1993[Opitz et al, , 1998Hunt and Hobar, 2002]. In addition, patients with NAFD often have further abnormalities of the branchial arches, including involvement of the auditory canal, the middle ear, and hypoplasia of the larynx [Opitz et al, 1993[Opitz et al, , 1998].…”

“…Antimongoloid palpebral fissures and eyelash dysgenesis can almost always be found [Opitz et al, 1993[Opitz et al, , 1998Hunt and Hobar, 2002]. In addition, patients with NAFD often have further abnormalities of the branchial arches, including involvement of the auditory canal, the middle ear, and hypoplasia of the larynx [Opitz et al, 1993[Opitz et al, , 1998]. Thus, the facial malformations show that NAFD is primarily or predominantly a defect of blastogenesis, presumably an abnormality of cranial neural crest development [Opitz et al, 1993;David et al, 1996].…”