Spondylo-ocular syndrome: a new entity with crystalline lens malformation, cataract, retinal detachment, osteoporosis, and platyspondyly.
OBJECTIVE
To define a new clinical entity in a consanguineous family with six children affected by a spondylo-ocular syndrome, including cataract, crystalline lens malformation, retinal detachment, osteoporosis, and platyspondyly. To analyze candidate genes of connective tissue disorders as a possible underlying disorder and to demonstrate especially the ocular phenotype.


METHODS
Observational case series.


METHODS
Consanguineous parents, one unaffected sibling and five affected children with clinical features of spondylo-ocular syndrome, were demonstrated. Clinical examination, radiologic, laboratory, and cytogenetic as well as moleculargenetic analyses were performed. The segregation of flanking marker alleles of three collagen genes and the interval for osteoporosis-pseudoglioma syndrome were analyzed. Two microsatellite markers located within Pax6CA/GT region were tested for homozygosity.


RESULTS
On laboratory investigation a normal excretion of amino acids, mucopolysaccharides, and oligosaccharides could be found. The karyotype was normal. Complete radiologic examination in one index patient revealed a generalized moderate osteoporosis, platyspondyly with fish bone appearance, and greatly enlarged intervertebral spaces. The candidate genes known to be in Stickler syndrome as well as linkage to the osteoporosis-pseudoglioma syndrome candidate region could be excluded. None of the affected showed homozygosity for the Pax6 microsatellite markers.


CONCLUSIONS
We conclude that the phenotype and the clinical features in this family defines a new Mendelian disorder. It remains to be seen what kind of molecule shared by eye and bone is involved.
Rudolph
Gunther
G
Department of Ophthalmology, LKKG-Kooperationsgruppe Ophthalmogenetik, Ludwig-Maximilians-University, Munich, Germany. Guenther.Rudolph@ak-i.med.uni-muenchen.de
Kalpadakis
Petros
P
Bettecken
Thomas
T
Lichtner
Peter
P
Haritoglou
Christos
C
Hergersberg
Martin
M
Meitinger
Thomas
T
Schmidt
Heinrich
H
D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D000328:Adult; D002386:Cataract / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D003094:Collagen / Q000235:genetics; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005136:Eye Proteins; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007908:Lens, Crystalline / Q000002:abnormalities* / Q000473:pathology; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D010024:Osteoporosis / Q000175:diagnosis / Q000235:genetics*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012097:Repressor Proteins; D012163:Retinal Detachment / Q000175:diagnosis / Q000235:genetics*; D013131:Spine / Q000002:abnormalities* / Q000473:pathology; D013577:Syndrome
D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D003094:Collagen