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

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. © 2005 Wiley‐Liss, Inc.

Nuchal cystic hygroma in five fetuses from 1819 to 1826 in the Meckel‐anatomical collections at the University of Halle, Germany

“…2 and 3. This type of incision is known from other preparations in which it is certain that Meckel the Younger did the autopsy [Klunker, 2003; Göbbel et al, 2005].…”

“…In the last few years, the collection, and in particular the anomalous human and animal fetuses were studied to identify the specimens described by Meckel the Younger and his students [Klunker, 2003]. DNA‐based molecular cytogenetic techniques, such as comparative genomic hybridization (CGH), were used in combination with radiographic techniques, computer tomography (CT), spiral CT, and magnetic resonance imaging (MRI) to reassess the diagnoses from a contemporary perspective and to compare these with the original diagnoses [Klunker et al, 2002, 2005; Tönnies et al, 2002, 2005; Göbbel et al, 2005]. The collection includes many malformations which Meckel the Younger called either anomalies of incomplete development or primary malformations ( die ursprünglichen Bildungsfehler ).…”

Nager Acrofacial Dysostosis Syndrome: A Newborn with Bilateral Hearing Impairment

“…Conductive deafness usually bilateral and problems with articulation is also noted in this syndrome 2 . Occasional abnormalities may comprise genitourinary abnormality, hypoplastic 1 st rib, downward pointing of ribs, lower lid coloboma and cleft lip 4 .…”