AUTOSOMAL DOMINANT INHERITANCE OF SCHMID'S METAPHYSEAL CHONDRODYSPLASIA : DESCRIPTION OF A NEW FAMILY, AND INVESTIGATION OF THE COL10A1 GENE. 874

Abstract

Schmid metaphyseal chondrodysplasia (SMCD; OMIM 156500) is a rare, inherited disorder of the skeleton that is manifested in early childhood by short stature, coxa vara and a wadling gait It was first described in 1943 in a Mormon kindred; affected individuals from this family were found to have a 13-basepair-deletion in the gene that codes for the α-1 chain of collagen X (COL10A1) 50 years later (Nat. Genet. 5: 79, 1993). 9 more mutations in the COL10A1 gene have been described since, in other kindreds. We describe a family with SMCD that was previously misdiagnosed as“X-linked hypophosphatemic rickets”. The mother, who has no affected relatives, is 36 years old (y.o.) and has a height of 149cm. She had bilateral coxa vara as a child and had three corrective surgeries of her lower extremities in her native Ukraine. She gave birth to two male children without any complications. The older boy is now a 7y.o with the height of a 3 1/2y.o; the younger sibling is now a 5 1/2y.o with the height of a 2 1/2y.o.. Both children have significantly bowed legs and coxa vara. Radiologic features included an enlarged and malformed femoral capital epiphysis with involvement of the distal femoral metaphysis in the older sibling, anterior rib mild changes, and a normal spine. Interestingly, both children had severe coxa vara before the age of 2 years, whereas their mother did not have any symptoms until her 5th year of life. This is consistent with the observation that presentation of SMCD in nonfamilial cases is no earlier than the second year of life; it may also represent gender-related differences in the expression of the disease, or simply significant variability in its phenotype. DNA was extracted from peripheral lymphocytes from the three affected individuals of this family and subjected to PCR-amplification by COL10A1 gene-specific primers, by standard methods. Single strand polymorphism conformation (SSCP) analysis of the COL10A1 gene is now underway in our laboratory, in order to identify the molecular defect causing SMCD in this family. We conclude that SMCD should be included in the differential diagnosis of lower extremities' abnormalities presenting in early childhood. SMCD is inherited in an autosomal dominant manner with significant variability in its clinical expression and is caused by mutations of the COL10A1 gene.