Human equivalent of mouse disorganization: Has the case been made?

Temtamy and McKusick suggested mouse disorganization (Ds) as a model for human tibial agenesis, fibular duplication and mirror foot, but the concurrent papers by Winter and Donnai and Donnai and Winter in 1989 kindled interest and led to continued reports of patients hypothesized as human equivalent of Ds (HEDs). Subsequent reports have tended to follow one or other of the two categories outlined; (1) band/constriction with additional anomalies unexplained by bands (ABS); (2) patterns of malformation interpreted as resembling mouse Ds (non-ABS). A review of a series of cases led to a re-read of the original Ds mouse reports by Hummel in 1958 and 1959 and examination of current literature in an attempt to assess the strength of the argument that the patients might represent HEDs. Key to the approach was a paragraph in Hummel's introduction; "some of the developmental anomalies … from action of Ds are similar to those caused by other …genes…teratogens… others are unique…" The corollary is a patient is likelier to represent human DS if the anomaly(s) match these unique malformations/patterns. Presence of anomalies not specifically noted in Ds would weaken the argument for human equivalence. Reports of possible HEDs were ascertained using PubMed and literature cited by authors subsequent to the 1989 papers, up to and including January, 2010. This paper gives an overview of HEDs patients reported and concludes that the ABS type, even with non-band associated anomalies, is not likely to often represent HEDs. Many non-ABS HEDs patients had equally valid alternative hypothesis or diagnoses, malformations unreported or unusual for the Ds mouse, and/or paucity of the more unusual anomalies of the Ds mouse.