Prenatal Genetics: Soft Markers, Congenital Anomalies, and Carrier Screening

Comprehensive vocabulary flashcards covering ultrasound soft markers, fetal structural malformations, congenital heart defect associations, chromosomal rearrangements, and prenatal carrier screening guidelines.

Renal pyelectasis

A dilation of the renal pelvis identified in approximately $4.5\%$ of ultrasounds; it is more prevalent in males than females, carries a $1.5$ relative risk for Down syndrome, and serves as an ultrasound marker for urinary tract abnormalities.

Increased nuchal fold

A second-trimester ultrasound finding measured as greater than $6\,\text{mm}$ above the mean; it is the strongest second-trimester soft marker for trisomy 21 and can indicate the resolution of a cystic hygroma in Noonan syndrome.

Echogenic bowel

A soft marker identified in about $1.5\%$ of ultrasounds whose differential diagnosis includes cystic fibrosis, cytomegalovirus (CMV) infection, intrauterine growth restriction (IUGR), intraamniotic bleeding, GI tract abnormalities, and trisomy 21.

Single umbilical artery

The most common congenital anomaly of the umbilical cord, found in approximately $1\%$ of all pregnancies, which only increases the risk for chromosomal abnormalities if identified alongside other fetal findings.

Ventriculomegaly

Dilation of the fetal cerebral ventricles found in $1\%$ of pregnancies; severe cases warrant consideration of mutations in L1CAM, while mild cases have a $90\%$ chance of normal neurodevelopment.

Genetic sonogram

A specialized second-trimester ultrasound examination assessing structural malformations and soft markers of Down syndrome, primarily serving to decrease the false-positive rate when combined with maternal serum screening.

Agenesis of the corpus callosum

A structural brain anomaly characterized by the congenital absence of the neural bridge connecting the cerebral hemispheres, attributable to chromosomal abnormalities or single-gene disorders.

Holoprosencephaly

A severe brain malformation resulting from the failure of the forebrain to divide into two distinct hemispheres; chromosomal abnormalities account for $20\%$ to $50\%$ of cases, with the remainder caused by single-gene disorders or teratogens.

Gastroschisis

An abdominal wall defect in which eviscerated abdominal contents are open and not contained within a protective sac, typically presenting as an isolated, sporadic, or multifactorial finding.

Omphalocele

A midline anterior abdominal wall defect where herniated viscera are enclosed within a membrane sac, demonstrating a strong association with trisomies 13, 18, and 21.

Clubfoot

A skeletal anomaly presenting in $1$ to $4$ per $1{,}000$ pregnancies that is more commonly bilateral and found more frequently in males; when seen in females or unilaterally, genetic suspicion is higher.

Pulmonary valve stenosis

An obstruction or narrowing of the pulmonary valve and outflow tract, classic for its clinical association with Noonan syndrome.

Supravalvular aortic stenosis

A localized narrowing of the ascending aorta above the level of the aortic valve, characteristically associated with Williams syndrome.

Ebstein's anomaly

A congenital tricuspid valve defect typically featuring an enlarged right atrium, classically linked prenatally to maternal lithium exposure.

Coarctation of the aorta

A congenital narrowing of the aortic lumen that is strongly associated with monosomy X (Turner syndrome).

Acrocentric chromosomes

Chromosomes possessing very short p arms and long q arms, consisting of human chromosomes 13, 14, 15, 21, and 22.

Robertsonian translocation

A chromosomal rearrangement involving centric fusion of two acrocentric chromosomes; $13;14$ is the most common overall ($75\%$), while $14;21$ is the most common form leading to Down syndrome.

Advanced paternal age

Paternal age defined between $40$ and $50$ years, which confers an increased risk of de novo single-gene dominant conditions (such as achondroplasia and Apert syndrome) in offspring, rather than chromosomal aneuploidy.

RhoGAM

An anti-D immune globulin administered to Rh-negative mothers at $28$ weeks of gestation, postpartum, and within $72\,\text{hours}$ of potential feto-maternal hemorrhage to prevent maternal Rh isoimmunization.

F508del

The most common pathogenic CFTR gene variant responsible for cystic fibrosis, resulting in a complete absence of residual CFTR channel function.

Spinal muscular atrophy (SMA)

The leading genetic cause of infant mortality, characterized in $95\%$ of affected individuals by homozygous deletions in SMN1, with phenotypic severity strongly influenced by SMN2 copy number.

Spinraza (nusinersen)

An FDA-approved therapeutic agent for children and adults with SMA that modulates SMN2 pre-messenger RNA splicing to promote the production of full-length, functional SMN protein.

Gaucher disease

An autosomal recessive lysosomal storage disorder that represents the most prevalent carrier condition among individuals of Ashkenazi Jewish ancestry, with a carrier rate of $1$ in $15$.