Rapid detection of K650E mutation in FGFR3 using uncultured amniocytes in a pregnancy affected with fetal cloverleaf skull, occipital pseudoencephalocele, ventriculomegaly, straight short femurs, and thanatophoric dysplasia type II.
OBJECTIVE
To present the ultrasound and molecular genetic diagnosis of thanatophoric dysplasia type II (TD2).


METHODS
A 35-year-old, primigravid woman was referred to our institution for genetic counseling and amniocentesis at 19 weeks of gestation because of advanced maternal age and sonographic abnormalities in the fetus. The prenatal ultrasound showed short straight femurs, prominent forehead, narrow chest, skin edema, short limbs, and cloverleaf skull consistent with the diagnosis of TD2. Amniocentesis revealed a karyotype of 46,XX. DNA testing for the FGFR3 gene using uncultured amniocytes revealed a heterozygous c.1948A>G, AAG>GAG transversion leading to a p.Lys650Glu(K650E) mutation in the FGFR3 gene. A prenatal ultrasound at 21 weeks of gestation showed ventriculomegaly, cloverleaf skull, straight femurs, micromelia, narrow chest, and pseudoencephalocele with a bulging occipital bone mimicking encephalocele. The pregnancy was subsequently terminated, and a 480-g malformed fetus was delivered with macrocephaly, depressed nasal bridge, short upturned nasal tip, hypoplastic midface, frontal bossing, short digits, trident-shaped hands, short limbs, cloverleaf skull, narrow chest, brachydactyly, nuchal edema, and bulging occipital bone.


CONCLUSIONS
A prenatal diagnosis of cloverleaf skull, short limbs, straight femurs, and occipital pseudoencephalocele should include a differential diagnosis of TD2. A molecular analysis of FGFR3 using uncultured amniocytes is useful for the rapid confirmation of TD2 at prenatal diagnosis.
Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan; Department of Medicine, Mackay Medical College, New Taipei City, Taiwan; Department of Biotechnology, Asia University, Taichung, Taiwan; School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; Institute of Clinical and Community Health Nursing, National Yang-Ming University, Taipei, Taiwan; Department of Obstetrics and Gynecology, School of Medicine, National Yang-Ming University, Taipei, Taiwan. Electronic address: cpc_mmh@yahoo.com.
Chih-Ping
CP
Chen
Tung-Yao
TY
Chang
Ming-Huei
MH
Lin
Schu-Rern
SR
Chern
Jun-Wei
JW
Su
Wayseen
W
Wang
D000328:Adult; D000650:Amnion / Q000166:cytology*; D003937:Diagnosis, Differential; D004677:Encephalocele / Q000000981:diagnostic imaging / Q000235:genetics*; D005260:Female; D005269:Femur / Q000002:abnormalities / Q000000981:diagnostic imaging; D006801:Humans; D006849:Hydrocephalus / Q000000981:diagnostic imaging / Q000235:genetics*; D009777:Occipital Bone / Q000002:abnormalities / Q000000981:diagnostic imaging; D017354:Point Mutation; D011247:Pregnancy; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics*; D012886:Skull / Q000002:abnormalities* / Q000000981:diagnostic imaging; D013796:Thanatophoric Dysplasia / Q000000981:diagnostic imaging / Q000235:genetics*; D014463:Ultrasonography
C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3
FGFR3; encephalocele; prenatal diagnosis; pseudoencephalocele; thanatophoric dysplasia type II