J Med Genet 1999;36:621-624 ( August )

Short report

Recessively inherited multiple epiphyseal dysplasia with normal stature, club foot, and double layered patella caused by a DTDST mutation Andrea Superti-Furga^a, Luitgard Neumann^b, Thomas Riebel^c, Georg Eich^d, Beat Steinmann^a, Jürgen Spranger^e, Jürgen Kunze^b

^a Division of Metabolic and Molecular Diseases, University Children's Hospital, Steinwiesstrasse 75, CH-8032 Zurich, Switzerland, ^b Institute of Human Genetics and Children's Hospital, Charité Campus, Humboldt University, Berlin, Germany, ^c Division of Paediatric Radiology, Charité Campus, Humboldt University, Berlin, Germany, ^d Division of Paediatric Radiology, University Children's Hospital, CH-8032 Zurich, Switzerland, ^e Children's Hospital, Gutenberg University, Mainz, Germany

Correspondence to: Dr Superti-Furga. asuperti{at}kispi.unizh.ch

Received 4 January 1999; Revised version accepted for publication 26 April 1999

We have observed over 25 different mutations in the diastrophic dysplasia sulphate transporter gene (DTDST) in association with the recessive disorders achondrogenesis 1B, atelosteogenesis 2, and diastrophic dysplasia. The c862t (R279W) transition is the most common mutation in non-Finnish patients, but in these disorders it is usually combined with other DTDST mutations. We had not seen a case of homozygosity for c862t (R279W) until we analysed DNA from a 36 year old male with tall-normal stature (180 cm) who asked for genetic counselling for suspected multiple epiphyseal dysplasia. He was treated for club foot and hip dysplasia at birth. Skeletal changes consistent with multiple epiphyseal dysplasia, with the peculiar finding of a double layered patella, were recognised during childhood. Cleft palate, swelling of the ear pinna, and hitch hiker thumb were absent. He was found to be homozygous, and both healthy parents heterozygous, for the R279W mutation in DTDST, and his fibroblasts showed a sulphate incorporation defect typical of DTDST disorders. Counselling was given for a recessive disorder, thereby considerably reducing the probability of affected offspring.
  Multiple epiphyseal dysplasia is more frequently caused by dominant mutations in the COMP (EDM1, McKusick 132400) and COL9A2 genes (EDM2, McKusick 600204). A few other patients and families with features similar to our proband have been described previously and considered to have autosomal recessive MED (EDM4, McKusick 226900). This observation confirms the existence of this entity and assigns it to the phenotypic spectrum associated with mutations at the DTDST locus.


Keywords: multiple epiphyseal dysplasia; DTDST; double layered patella

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© 1999 by J Med Genet
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