A disorder resembling pseudoachondroplasia but without COMP mutation.
Pseudoachondroplasia (PA) is an autosomal dominant skeletal dysplasia characterized by disproportionate short stature, generalized ligamentous laxity, irregular epi-metaphyseal ossification, and vertebral anomalies that regress with age. It usually manifests in the second year of life or later. The clinically and radiographically variable disorder is caused by mutations in the COMP gene. Parental gonadal mosaicism may lead to recurrence of the disorder in children of unaffected parents. Here, we describe sibs with bone changes similar to those seen in very severe PA born to clinically and radiographically unaffected parents. Sequencing of all 19 exons of the COMP gene failed to disclose a mutation. The sibs appear to be affected by a disorder resembling PA but resulting from a defect of an extracellular matrix protein other than COMP. It may be suspected in patients with unusually severe dwarfism, severe epi-metaphyseal abnormalities, and persistent platyspondyly.
Spranger
J W
JW
Children's Hospital, University of Mainz, Germany. spranger@ggc.org
Zabel
B
B
Kennedy
J
J
Jackson
G
G
Briggs
M
M
D000130:Achondroplasia / Q000235:genetics / Q000473:pathology*; D000328:Adult; D064236:Cartilage Oligomeric Matrix Protein; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008297:Male; D064235:Matrilin Proteins; D009154:Mutation; D010009:Osteochondrodysplasias / Q000235:genetics / Q000473:pathology*; D035781:Siblings
D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D064235:Matrilin Proteins; C577553:TSP5 protein, human; D004247:DNA