Advances in Genetics: The Role of Genetics in the Management of Fetal Neck Masses

Published on in In Utero Insights

A focal point for every family that is cared for in the Center for Fetal Diagnosis and Treatment is to assess for a  genetic basis for the findings in the fetus. Through evaluation with a genetic counselor and a reproductive genetic specialist, our families receive comprehensive risk assessment based upon the physical findings in the fetus, such as a neck mass, as well as risk factors in their family, and a medical and pregnancy history.

Fetal neck masses describe a large group of conditions that can be challenging for both a clinician and family. At The Children’s Hospital of Philadelphia, we feel that establishing a diagnosis, including the underlying pathophysiology, and evaluating for associated genetic syndromes is crucial as they directly relate to management and prognosis.

Understanding the position and location of the neck mass can be helpful in determining a diagnosis. Common anterior neck masses include teratoma, lymphangiomas, goiter and hemangiomas. Common posterior neck masses include cystic hygroma, cervical meningocele, encephalocele, hemangioma and lymphangiomas. Characteristics such as vascularity, solid or cystic nature, presence of calcifications, and septations are paramount in establishing a diagnosis. A comprehensive evaluation of the fetus assessing for additional anomalies, hydrops or polyhydramnios also helps to provide clinical clues as to the underlying pathophysiology of the diagnosis.

The most common fetal neck mass — cystic hygroma — can be identified at 11 to 12 weeks gestation during the nuchal translucency scan. They occur in approximately 1 in 285 first trimester pregnancies. Cystic hygromas identified in the first trimester are associated with chromosomal abnormalities in up to 60 percent of cases. Of those with a normal karyotype, one-third will have a major structural anomaly, most commonly cardiac defects. Therefore, in all cases of cystic hygroma, fetal echocardiogram is warranted.

When diagnosed in the second or third trimester, cystic hygromas are often characterized as lymphangiomas and carry a slightly reduced risk of chromosomal abnormality, but may be associated with single-gene disorders such as Noonan syndrome, Fryns syndrome, multiple pterygium syndrome, Roberts syndrome and Cornelia de Lange syndrome. Additionally, lymphangioma has been seen as an isolated autosomal recessive trait that can be more common in consanguineous families.

Unlike cystic hygromas, many other fetal neck masses are not detected until much later in the pregnancy. Many of these findings in isolation carry much less of a genetic association.

Just as prenatal imaging is imperative to establishing the diagnosis of fetal neck mass, genetic testing can be crucial to determining prognosis, availability of fetal interventions and recurrence risk for a family. While a karyotype remains the test with the highest diagnostic yield in detecting genetic etiology of neck mass, a normal karyotype does not mean a genetic evaluation is complete. Careful consideration of fetal anatomy, family history and consanguinity is necessary to determine if further genetic testing for single-gene disorders is needed or an autosomal recessive trait exists.