Newly recognized autosomal recessive acrofacial dysostosis syndrome resembling Nager syndrome

Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Ontario, Canada.
American Journal of Medical Genetics Part A (Impact Factor: 2.16). 08/2004; 129A(1):73-6. DOI: 10.1002/ajmg.a.30113
Source: PubMed


We report on two patients with a unique constellation of anomalies resembling the Nager acrofacial dysostosis syndrome. Clinical manifestations which differentiate their condition from Nager syndrome include: microcephaly, cleft lip and palate, a peculiar beaked nose, blepharophimosis, microtia, symmetrical involvement of the thumbs, and great toes and developmental delay. We postulate that the inheritance is autosomal recessive on the basis of similarly affected male and female sibs. (C) 2004 Wiley-Liss, Inc.

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    • "Appendicular involvement, usually limited to the upper limbs, is considered the hallmark of AFD1 and allows differentiation from other AFDs, such as Miller syndrome [Halal et al., 1983; Opitz, 1987]. For decades, the molecular basis of AFD1 remained unknown, with most cases occurring sporadically and rarely clustering in families and therefore being compatible with both autosomal dominant and recessive transmission [Chemke et al., 1988; Hall, 1989; Aylsworth et al., 1991; McDonald and Gorski, 1993; Kennedy and Teebi, 2004]. Bernier et al. [2012] identified 18 different heterozygous mutations in the SF3B4 gene in "
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    ABSTRACT: Nager syndrome, or acrofacial dysostosis type 1 (AFD1), is a rare multiple malformation syndrome characterized by hypoplasia of first and second branchial arches derivatives and appendicular anomalies with variable involvement of the radial/axial ray. In 2012, AFD1 has been associated with dominant mutations in SF3B4. We report a 22-week-old fetus with AFD1 associated with diaphragmatic hernia due to a previously unreported SF3B4 mutation (c.35-2A>G). Defective diaphragmatic development is a rare manifestation in AFD1 as it is described in only 2 previous cases, with molecular confirmation in 1 of them. Our molecular finding adds a novel pathogenic splicing variant to the SF3B4 mutational spectrum and contributes to defining its prenatal/fetal phenotype.
    Molecular syndromology 08/2014; 5(5):241-4. DOI:10.1159/000365769
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    • "Moreover, radiographic examination of the fetus we studied, showed ribs pointing downwards, hypoplastic clavicle, and ankylosis of the shoulder joint on both sides, however, no hemivertebrae, vertebral hypoplasia, or block vertebral anomalies , thus excluding Goldenhar anomaly. The NAFD is a genetically heterogeneous disorder with different patterns of transmission among families (e.g., autosomal dominant, autosomal recessive) [Aylsworth et al., 1991; Bonthron et al., 1993; Opitz et al., 1993; Zori et al., 1993; Kennedy and Teebi, 2004]. However, in most cases NAFD occurs sporadically [Opitz et al., 1993]. "
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    ABSTRACT: The Anatomical Collections of the Department of Anatomy and Cell Biology at the University of Halle, Germany, comprise more than 8,000 specimens, about 600 of them congenital anomalies. The collection of abnormal human and animal specimens began with the private collections of Johann Friedrich Meckel the Elder (1724-1774), his son Philipp Friedrich Theodor Meckel (1755-1803), and his grandson Johann Friedrich Meckel the Younger (1781-1833). Meckel the Younger founded the science of developmental pathology in Germany. Radiographical techniques, computer tomographic methods (CT), magnetic resonance imaging (MRI), and molecular cytogenetic techniques, for example, comparative genomic hybridization (CGH) were used to diagnose abnormal human fetuses in the Meckel Collection. On examination of one of the human fetuses, originally described by JF Meckel the Younger in 1812 or earlier, we found striking clinical manifestations including mandibulofacial defects and preaxially malformed limbs. With respect to external findings, we propose that the condition is acrofacial dysostosis (AFD) with preaxial limb hypoplasia (Nager AFD) in combination with club foot, tibial torsion, and single umbilical artery. We used genetic analyses to test whether the observed limb malformations could be caused by aneuploidy. CGH-ratio profiles of all chromosomes were apparently normal. It is likely that Meckel's specimen is the earliest known fetus with Nager AFD.
    American Journal of Medical Genetics Part A 09/2005; 137A(3):263-8. DOI:10.1002/ajmg.a.30889 · 2.16 Impact Factor
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    Journal of Medical Genetics 10/1993; 30(9):779-82. DOI:10.1136/jmg.30.9.779 · 6.34 Impact Factor
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