Early ultrasound suspect of thanatophoric dysplasia followed by first trimester molecular diagnosis

Abstract

[No abstract available

Evaluation of first trimester ultrasound fetal biometry ratios femur length/biparietal diameter, femur length/abdominal circumference and femur length/foot for the screening of skeletal dysplasia

“…Measurement of the fetal foot was performed retrospectively and not during the NT scan session which is prone to bias despite that those measurements were obtained unknowingly corresponding to cases or controls. Compared to other publications that reported a higher rate of diagnosis of skeletal dysplasia in the first trimester, 7,8,17 the majority of our cases were diagnosed with skeletal dysplasia after but not during the NT scan;…”

“…Few case reports identified extremely shortened femur with or without thickened NT at 11-12 weeks' gestation as the initial sonographic finding prompting molecular testing to confirm skeletal dysplasia. 7,8,17 In our study, we observed that pregnancies affected by skeletal dysplasia especially of lethal types had shortened femur during the NT screen. However, we consider that unless an extremely shortened or distorted femur also is identified, relying solely on a first trimester FL to screen for skeletal dysplasia is not practical since most available biometric charts including FL begin at 14 weeks' gestation.…”

“…Several sonographic measurements including nuchal translucency (NT), femur length (FL) alone, FL to abdominal circumference (AC) and cardiothoracic ratio have been used to predict skeletal dysplasia, but they usually become applicable in the mid-second trimester when these disorders become apparent. [6][7][8][9] The FL/foot ratio is an underutilised ratio despite proven validity in the screening of abnormally shortened femurs in the second and third trimesters. 10 FL/foot remains constant from the second trimester throughout the pregnancy to a ratio of one (lower limit 0.87), and it is not affected by gestational age though its validity in the first trimester has not been tested.…”

Molecular Analysis of a Case of Thanatophoric Dysplasia Reveals Two de Novo FGFR3 Missense Mutations located in Cis

“…The earliest radiological signs are increased nuchal thickness and short limbs, but these signs are nonspecific. 5,6 A molecular diagnosis may be made prenatally if genetic testing for TD is requested on deoxyribonucleic acid (DNA) extracted from a chorionic villus or amniocentesis sample, but is more commonly made following a post-mortem examination carried out to clarify the nature of the lethal skeletal dysplasia in question. 5,6 TD is primarily an autosomal dominant disorder, resulting from heterozygous mutations in the FGFR3 gene that lead to ligand-independent activation of the receptor and disruption of cartilage function during linear bone growth.…”

“…5,6 A molecular diagnosis may be made prenatally if genetic testing for TD is requested on deoxyribonucleic acid (DNA) extracted from a chorionic villus or amniocentesis sample, but is more commonly made following a post-mortem examination carried out to clarify the nature of the lethal skeletal dysplasia in question. 5,6 TD is primarily an autosomal dominant disorder, resulting from heterozygous mutations in the FGFR3 gene that lead to ligand-independent activation of the receptor and disruption of cartilage function during linear bone growth. 7 Mutations in the FGFR3 gene cause a spectrum of skeletal dysplasias ranging from the relatively mild hypochrondroplasia through to achondroplasia, severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN), and thanatophoric dysplasia.…”