Detection of a de novo Y278C mutation in FGFR3 in a pregnancy with severe fetal hypochondroplasia: prenatal diagnosis and literature review.

[achondroplasia]

We describe a prenatal molecular diagnosis of hypochondroplasia (HCH ) in a pregnancy not at risk of HCH and review the literature on prenatal diagnosis of HCH .A 28 -year -old primigravid woman was referred for genetic counseling at 30 weeks of gestation because of short-limbed dwarfism in the fetus . The woman had a body height of 152 cm . Her husband had a body height of 180 cm . Level II ultrasound showed a normal amount of amniotic fluid and a singleton fetus with fetal biometry equivalent to 30 weeks except for short limbs . Fetal biometry measurements were as follows : biparietal diameter = 7 .38 cm (30 weeks ); head circumference = 28 .14 cm (30 weeks ); abdominal circumference (AC ) = 24 .64 cm (30 weeks ); femur length (FL ) = 3 .97 cm (<5 th centile ); FL /AC ratio = 0 .161 (normal > 0 .18 ); humerus = 3 .64 cm (<5 th centile ); radius = 3 .49 cm (30 weeks ); ulna = 3 .76 cm (<5 (th ) centile ); tibia = 3 .67 cm (<5 th centile ); and fibula = 3 .72 cm (<5 th centile ). The digits and craniofacial appearance were normal . A tentative diagnosis of achondroplasia (ACH ) was made . DNA testing for the FGFR 3 gene and whole-genome array comparative genomic hybridization (aCGH ) analysis were performed using cord blood DNA obtained by cordocentesis . FGFR 3 mutation analysis revealed a de novo heterozygous c .833 A > G , TAC > TGC transversion in exon 7 leading to a p .Tyr 278 Cys (Y 278 C ) mutation in the FGFR 3 protein . aCGH analysis revealed no genomic imbalance in cord blood . After delivery , the fetus had short limbs , a narrow thorax , brachydactyly , and relative macrocephaly . Cytogenetic analysis of cultured placental cells revealed a karyotype of 46 ,XX .Prenatal diagnosis of abnormal ultrasound findings suspicious of ACH should include a differential diagnosis of HCH by molecular analysis of FGFR 3 .

Diseases
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Diseases presenting "craniofacial appearance" symptom

achondroplasia

cohen syndrome

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