Little GuyMGA2-05-13

Achondroplasia, an autosomal dominant trait

    Achondroplasia is a class of skeletal growth syndromes characterized by short stature due to slow development of the middle portions of the long bones in the arms and legs. The most common form of achondroplasia (left) is due to a defect of the Fibroblast Growth Factor Receptor (FGFR), and is recognized by exaggerated cranial growth and bossing (depression) at the bridge of the nose. A second form is pseudoachrondroplasia (right), which is due to a defect of Cartilage Oligomeric Matrix Protein (COMP) in the joints, and is characterized by more typical development of cranial proportions. Both forms are described as sporadic, meaning that they occurs in different families due to independent mutations. Thus, most affected children are born to parents of ordinary stature, one of whom has a germline mutation. In the children of two parents with achondroplasia (Dd x Dd), most affected offspring are heterozygous (Dd),  which suggests that the homozygous dominant genotype (DD) is lethal.

    Shown on the right are seven pseudoachondroplasic members of the Ovitz family, a family of Romanian Jews who toured eastern Europe as a musical troupe before World War II (their taller siblings working backstage), survived imprisonment at Auschwitz, and finally emigrated to Israel. They were photographed on arrival in Haifa in 1949. Their father was (apparently) of ordinary height and was twice married, both times to women of ordinary height. With his first wife, he had two affected daughters [possibly the two older women in flowered dresses], and with his second five affected children (three girls and two boys) shown here, as well as three children of ordinary height. This suggests the father had a germline mutation p P, in which case the expected ratio from Pp x pp 50% "P" : 50% "p", as compared with the observed ratio of 7 affected : 3 unaffected children. Note that this departure from expectation is the same ratio of girls to boys. [Homework: test the ratios by chi-square and 2x2 contingency tests]. The sons are reported to have had taller children (Pp x pp 50% "pp"); the daughters were unable to bear children because of their narrow pelvises.

The father was Shimson Eizik Ovitz. The children from his first wife Brana Fruchter were
Rozik (affected)
Franzika (affected)
The children from his second wife Batia Bertha Husz were
Avram (affected)
Freida (affected)
Sarah (unaffected)
Micki (affected)
Leah (unaffected)
Elizabeth (affected)
Arie (unaffected)
Piroska ("Perla") (affected)

Figure ©2002 by Griffiths et al;. all text material ©2011 by Steven M. Carr