New aids for the non‐invasive prenatal diagnosis of achondroplasia: dysmorphic features, charts of fetal size and molecular confirmation using cell‐free fetal DNA in maternal plasma

Abstract

Objectives To improve the prenatal diagnosis of achondroplasia by constructing charts of fetal size, defining frequency of sonographic features and exploring the role of non-invasive molecular diagnosis based on cell-free fetal deoxyribonucleic acid (DNA) in maternal plasma. Methods

Generalized Disorders and Syndromes of Orthopedic Importance

“…Over 95 % of cases are caused by one of two recurrent mutations in the gene encoding fi broblast growth factor receptor type 3 (FGFR3), both resulting in the same amino acid substitution (G380R). Prenatal US by 25 weeks can show short femurs (often below the 3rd percentile) [ 74 ] along with a head size of greater than the 50th percentile, bowed femurs, frontal bossing, small chest, and polyhydramnios. Diagnosis at birth is based upon the clinical fi ndings of predominantly rhizomelic limb shortening, dysmorphic features, a prominent forehead, and depressed nasal bridge.…”

Prenatal Evaluation of Fetuses Presenting with Short Femurs

“…Prenatal sonographic diagnosis is often not possible as the length of long bones is well preserved until around 22 weeks' gestation, the time of the routine fetal anomaly scan. (Goncalves & Jeanty, 1994;Chitty et al, 2011) The FL is at the fifth percentile at this time and then below the first percentile at about 30 weeks. (Nyberg, 2003) Presentation and diagnosis of de novo cases often occurs at this period when the short limbs, frontal bossing and trident hand may be evident.…”

Societal Aspects: Ethics

“…The first clinical applications of NIPD have included fetal sex determination [4], Rhesus D genotyping in mothers who are Rhesus D (RhD) negative [5] and paternally inherited single gene disorders or conditions arising de novo, such as achondroplasia [6]. NIPD for recessively inherited single gene disorders where both parents carry the same mutation or for X-linked conditions is more complex as there are high circulating levels of mutant DNA emanating from the mother.…”