Genetic skeletal disorders of the fetus and infant: pathologic and molecular findings in a series of 41 cases.
BACKGROUND
Genetic skeletal disorders of the fetus and infant are a large group of genetic disorders, comprising the groups formerly assigned as skeletal dysplasias (osteochondrodysplasias), dysostoses, and malformation syndromes with a skeletal component. Genetic skeletal disorders may be prenatally detected by ultrasonography or result in intrauterine or early postnatal death, constituting one difficult diagnostic field met by the pathologist who performs the perinatal autopsy.


METHODS
In this retrospective study, we have gathered radiologic, physical, histopathologic, and molecular data regarding 41 cases of genetic skeletal disorders diagnosed among 1980 fetal and perinatal autopsies over a 10-year period.


RESULTS
Our series of cases were classified according to the 2006 Nosology and Classification of Genetic Skeletal Disorders. The overall frequency of genetic skeletal disorders was 1:48 autopsies. The FGFR3 group and osteogenesis imperfecta type 2 were the more frequently encountered disorders. The mean gestational age at autopsy was 21.9 weeks (range, 12-37 weeks). A final diagnosis was obtained in 95% of cases. Genetic skeletal disorders were detected by prenatal ultrasound in 90% of cases, with a correct typing of the disorder achieved in only 34%. Molecular analysis was confirmative in 5 cases.


CONCLUSIONS
The central role of the perinatal pathologist in collaboration with specialized services is essential for the correct interpretation of the radiologic, physical, and histopathologic findings, to accurately classify specific types of genetic skeletal disorders and enable genetic counseling.
Konstantinidou
Anastasia E
AE
Department of Pathology, Medical School, National Kapodistrian University of Athens, Greece. ankon@med.uoa.gr
Agrogiannis
Georgios
G
Sifakis
Stavros
S
Karantanas
Apostolos
A
Harakoglou
Vassileios
V
Kaminopetros
Petros
P
Hatzaki
Angeliki
A
Petersen
Michael B
MB
Karadimas
Charalampos
C
Velissariou
Voula
V
Velonis
Stylianos
S
Papantoniou
Nikolaos
N
Antsaklis
Aristeidis
A
Patsouris
Efstratios
E
D001344:Autopsy; D001847:Bone Diseases / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D005315:Fetal Diseases / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D006801:Humans; D009154:Mutation; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics; D012189:Retrospective Studies; D016216:Ultrasonography, Prenatal
C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3