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 "prenatal diagnosis" symptom

22q11.2 deletion syndrome

achondroplasia

adrenomyeloneuropathy

alexander disease

alpha-thalassemia

aromatase deficiency

benign recurrent intrahepatic cholestasis

cadasil

canavan disease

classical phenylketonuria

cohen syndrome

congenital adrenal hyperplasia

congenital diaphragmatic hernia

congenital toxoplasmosis

cystinuria

dentinogenesis imperfecta

epidermolysis bullosa simplex

harlequin ichthyosis

holt-oram syndrome

homocystinuria without methylmalonic aciduria

hydrocephalus with stenosis of the aqueduct of sylvius

junctional epidermolysis bullosa

kindler syndrome

krabbe disease

lamellar ichthyosis

megacystis-microcolon-intestinal hypoperistalsis syndrome

monosomy 21

neonatal adrenoleukodystrophy

oculocutaneous albinism

omenn syndrome

phenylketonuria

primary hyperoxaluria type 1

pyruvate dehydrogenase deficiency

severe combined immunodeficiency

wolf-hirschhorn syndrome

x-linked adrenoleukodystrophy

zellweger syndrome

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