Skeletal dysplasias with gracile bones: three new cases, including two offspring of a mother with a dwarfing condition.
We describe 3 new cases of a rare form of dwarfism (so-called "lethal skeletal dysplasia with gracile bones" or "osteocraniostenosis"), a condition characterized by thin, brittle bones and death in late gestation or early neonatal life. The first was a 37-week gestation female who died at delivery. She had facial anomalies and positional abnormalities of the hands and feet. The others were male stillborn sibs, who died in utero in the third trimester. Their mother had an undiagnosed dwarfing condition associated with body asymmetry, microcephaly, and unusual facial appearance. Both fetuses were documented by ultrasound to have short limbs and probable long bone fractures late in the second trimester. At autopsy, one fetus had no spleen and the other a hypoplastic spleen. Radiographically, all three cases had very thin diaphyses, diaphyseal fractures, and thin ribs and clavicles. In contrast to the first case who had a normally mineralized calvaria, the sibs had grossly deficient calvarial mineralization. Microscopically, endochondral ossification was qualitatively normal but quantitatively deficient in all three cases. The long bones, especially those of the sibs, lacked the well-defined outer cortex in the mid-shaft normally seen by the third trimester. This failure of organization into the cortex and medulla suggests a failure of bone remodelling. Given the variable presentation in these cases, "lethal skeletal dysplasia with gracile bones" is probably a heterogeneous disorder. The recurrence in one family suggests that the mother has somatic/germline mosaicism of a lethal gene, expressed clinically as growth failure and asymmetry.
Costa
T
T
Department of Pediatrics and Genetics, Hospital for Sick Children, Toronto, Canada. teresa.costa@dal.ca
Azouz
E M
EM
Fitzpatrick
J
J
Kamel-Reid
S
S
Smith
C R
CR
Silver
M M
MM
D000328:Adult; D000483:Alleles; D001848:Bone Diseases, Developmental / Q000235:genetics / Q000473:pathology*; D019465:Craniofacial Abnormalities / Q000235:genetics / Q000473:pathology; D004247:DNA / Q000737:chemistry; D004392:Dwarfism / Q000235:genetics / Q000473:pathology*; D005260:Female; D005313:Fetal Death / Q000235:genetics / Q000473:pathology; D005865:Gestational Age; D006226:Hand Deformities / Q000235:genetics / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D009030:Mosaicism; D015513:Oncogene Proteins / Q000235:genetics; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D011518:Proto-Oncogene Proteins; D013131:Spine / Q000002:abnormalities
D018398:Homeodomain Proteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; C071250:TLX1 protein, human; D004247:DNA