Ultrasound Evaluation of the Fetal Face and Neck

Typical Facial Clefts

Orofacial clefts are relatively common and occur in 1 in 700 live births. The rate varies by ethnicity, with higher rates seen in Asian and Native American populations and significantly lower rates in African populations. Typical facial clefts can occur as isolated cleft lip (CL), isolated cleft palate (CP), or as a combination of both cleft lip and cleft palate (CL+CP). They are often further subdivided into the categories of CL±CP and isolated CP. Clefts most often run from one or both of the nostrils to the central part of the posterior palate. An in-depth anatomic classification system was proposed by Tessier in 1976.

Of all orofacial clefts, CL with CP represents 50% of cases, isolated CL 25% of cases, and isolated CP 25% of cases. Clefts involving the lip are more common in males, with a ratio of 2 : 1, and isolated CP clefts are more common in females, also with a ratio of 2 : 1. A large study of almost 50,000 deliveries in Norway with 77 fetuses with CL±CP revealed that among cases of CL±CP, 64% were unilateral and 34% were bilateral, with only 3% being midline. The same study demonstrated that in unilateral clefts, 69% were left-sided and 31% were right-sided, with a ratio of 2.3 : 1. The left-sided predominance has also been shown in other studies; however, there is no definitive anatomic explanation for this finding. Median clefts have unique causes and associations and are detailed in the next section (“ Atypical Facial Clefts ”).

An appreciation for the embryologic development of the face can help in the understanding of the development of orofacial clefts. The face arises from five prominences that surround the mouth—the central frontonasal prominence and the paired maxillary and mandibular prominences. These prominences are composed of neural crest cells and are present by the fourth week of embryogenesis ( Fig. 10-8 ). By the fifth week, the nasal placodes have formed, separating each side of the inferior portion of the frontonasal prominence into lateral and medial nasal processes. The upper lip and primary palate are formed by the end of the sixth week, when the medial nasal processes fuse with each other and the paired maxillary processes. This sixth week is a sensitive time for development, and teratogenic exposures at this time can result in orofacial clefts. The purpose of the secondary palate is to separate the oral and nasal cavities. The development of the secondary palate begins in the sixth week and is completed by the tenth week. The secondary palate is formed from paired palatal shelves that are outgrowths of the maxillary processes. These shelves fuse during the seventh week and differentiate into the hard and soft palate. By the tenth week, the primary palate and nasal septum have fused with the secondary palate ( Fig. 10-9 ). Clefting can occur during multiple stages of the embryogenesis process and results in different anatomic variations depending on the timing and which prominences are affected ( Fig. 10-10 ).

Orofacial clefts are often divided into the categories of syndromic and nonsyndromic clefts. In CL±CP, 70% to 90% of clefts are nonsyndromic, and in isolated CP, 60% to 80% of clefts are nonsyndromic. Isolated CL should be counseled similarly to CL+CP because it has a similar developmental pattern. Table 10-4 reviews some of the more common syndromic associations with orofacial clefts. It is essential that parents with fetuses with the prenatal diagnosis of orofacial clefts be offered further genetic workup with chorionic villus sampling or amniocentesis and evaluation of chromosomal abnormalities with karyotyping and chromosomal microarray.

All types of orofacial clefts can potentially be associated with other structural anomalies. In one study, 43% of those with CL±CP and 58% of those with isolated CP had associated structural anomalies. Rates of associated anomalies vary, with another study reporting 35% of patients with CL±CP as having an associated anomaly or suspected genetic syndrome. A third study suggested a lower level of association with anomalies, reporting that those with unilateral CL±CP had a rate of associated structural anomalies of 9.8%, whereas bilateral CL+CP had associated anomalies in 25%. Most of these studies are biased by tertiary care subselection; in our practice, we counsel a risk of associated anomalies of approximately 10% when an isolated CL±CP is identified on prenatal ultrasound images.

In addition to genetic causes, orofacial clefts have been linked to several environmental factors and medications. Organic solvent and agricultural chemical exposure may contribute to the risk for cleft anomalies. Antiepileptic medications, including the older generation drugs such as diazepam, phenytoin, and phenobarbital as well as some of the newer generation drugs such as topiramate and lamotri­gine have been associated with an increased risk of orofacial clefts in some studies. Early exposure to retinoid medications and corticosteroids has also been linked to fetal craniofacial anomalies. Maternal smoking has been consistently associated with CL±CP with a relative risk of 1.34 and CP alone with a relative risk of 1.22 in a large meta-analysis. There is inconsistent evidence suggesting that folic acid deficiency may yield an increased risk for orofacial clefts and thus that supplementation could potentially decrease the risk of recurrence in a subsequent pregnancy, but this relationship has not been definitively established. The early prenatal use of multivitamins has been associated with a 25% reduction in the risk for CL±CP and a nonsignificant 12% reduction in the risk for CP.

Prenatal diagnosis of clefts can allow parents to choose options for further genetic testing and can also prepare them for the child's medical course if they continue the pregnancy. In 1981, Christ and Meininger reported the first prenatal ultrasonographic diagnosis of an orofacial cleft. Research has demonstrated that the detection of clefts has improved over time, with one study citing a detection rate of 34% in the period of 1987-1995 and 58% in the period of 1996-2004. A systematic review of 21 studies reported a broad range in prenatal detection rates for low-risk women, from 9% to 100% for CL±CP and 0% to 22% for CP only. Detection of isolated CP in particular continues to be poor, with some large contemporary studies showing a detection rate of 0%.

In the second trimester, CL±CP and CP can be best visualized by utilizing both coronal and axial planes. In the anterior coronal plane, with a view of both the nose and lips, a CL is identified as a defect extending from one nostril to the oral rim ( Table 10-5 ). These defects can cause distortion of the upper lip and nose, which can be seen well with a 3D rendered image ( Fig. 10-11 ). To determine whether the defect extends into the alveolus or the primary palate, the axial plane is the best approach ( Table 10-6 ). This view can demonstrate the extent of the cleft and determine if it also involves the secondary or hard palate ( Fig. 10-12 , Table 10-7 ). As discussed, identifying an isolated CP is quite challenging, and these defects are often missed, even with thorough 2D or 3D ultrasonography. In the case of bilateral CL+CP, the sagittal plane with the fetal profile can be helpful. This view can demonstrate the protrusion of the central palate and lip, often termed the premaxillary mass ( Fig. 10-13 ). The sagittal plane will likely be normal in cases of unilateral CL+CP or with bilateral CL. When any type of orofacial cleft is suspected, 3D ultrasound can often offer a more accurate portrayal of the facial anatomy and specifically the hard and soft palate ( Figs. 10-14 and 10-15 ). As previously reviewed, the “flipped face” and the “reversed face” view allow the examiner to evaluate the posterior hard and soft palates. MRI may better illustrate the extent of orofacial clefting, as it allows for improved visualization of the palate, particularly the hard or secondary palate.

Prenatal diagnosis of orofacial clefts in the first trimester has been reported by Sepulveda and associates. It has been proposed that the RNT view may be a useful diagnostic tool. This view is a coronal image of the fetal face posterior to the nose that includes the three echogenic lines formed by the two frontal processes of the maxilla and the palate ( Fig. 10-16 ). A hypoechoic defect in the palate region can be indicative of an orofacial cleft.

The prognosis of orofacial clefts depends first and foremost on the presence of associated anomalies or genetic syndromes. Feeding, respiratory function, and speech attainment may be compromised with all clefts, particularly those involving the palate. The cosmetic appearance can also be debilitating to a child's psychological and social development. A multidisciplinary approach is a necessity with the involvement of nursing, plastic surgery, maxillofacial surgery, otolaryngology, speech therapy, audiology, counseling, genetics, orthodontics, and dentistry. The American Cleft Palate–Craniofacial Association 2009 guidelines recommend surgical repair of a CL in the first 12 months of life and surgical palate repair by 18 months, or earlier if possible. Most children with CL and CP will undergo approximately 10 surgeries (related to the cleft and tubes for ears) by the age of 10 years.

Recurrence of orofacial clefts tends to be type-specific, with either a history of CL±CP or isolated CP within the same familial line. In a large study of over 54,000 relatives from 1952 to 2005, the recurrence risk in those with first-degree relatives with orofacial clefts was 3.5% (95% confidence interval 3.1-4.0%). Table 10-8 details the approximate recurrence risks for various degrees of familial relationships. Despite the hereditary risk factors, the majority of orofacial clefts are sporadic.

Atypical Facial Clefts

Median and lateral facial clefts are far less common than the typical clefts reviewed earlier. Only about 3% of clefts are located at the midline. Median or midline clefts are associated with two distinct phenotypes: (1) the median cleft, which is often associated with holoprosencephaly, and (2) frontonasal dysplasia or median cleft face syndrome.

The processes of midline and facial defects and brain development are closely linked. Inadequate development of the frontonasal prominence can result in a midline facial defect. This is often correlated with holoprosencephaly, a process in which the embryonic forebrain has incomplete cleavage. In 1964, DeMyer and coworkers described the spectrum of facial phenotypes that can accompany holoprosencephaly, which can range from a median quadrangular CL±CP with orbital hypotelorism and a flattened nose to cyclopia with arhinia and a proboscis ( Figs. 10-17 through 10-19 ). The degree of facial dysmorphism is often reflective of the degree of holoprosencephaly.

The prognosis of median clefts associated with holoprosencephaly is universally poor. The majority of the time, the condition will be lethal and the few survivors are affected by significant neurodevelopmental disability. Holoprosencephaly occurs in 1 in 8000 live births, with chromosomal abnormalities, most commonly trisomy 13, present in 37% to 67% of cases.

The second phenotype associated with median facial clefts is frontonasal dysplasia or the median cleft face syndrome. In contrast to the hypotelorism and midline clefts associated with holoprosencephaly, this condition instead presents with hypertelorism and the unique features of median clefting affecting the nose or both the nose and lip or palate, broadening of the nasal root, with unilateral or bilateral colobomas of the nasal alae, lack of formation of the nasal tip, anterior cranium bifidum occultum, and a widow's peak hair distribution. The identification of hypertelorism on ultrasound image in the axial scan differentiates this condition from the median cleft associated with holoprosencephaly. Prenatal ultrasonographic diagnosis has been reported as early as the first trimester, utilizing 3D ultrasonography.

The prognosis for patients with median cleft face syndrome depends on the severity of the defects and also on the presence of any central nervous system malformations. Patients with median cleft face syndrome usually do not typically present with developmental disability, though one small series of 21 patients cited a prevalence of neurodevelopmental abnormalities in approximately 50% of cases, associated with a high frequency of agenesis of the corpus callosum. The surgical correction of these multiple facial malformations, including the midline defect as well as the hypertelorism, can be a significant undertaking.

Lateral facial clefts are another form of atypical facial cleft. They often begin at the corners of the mouth and extend outward, with the most severe forms reaching the ear. These anomalies occur in 1 in 50,000 to 1 in 175,000 live births. Such clefts, like the typical clefts, may develop as errors of early embryogenesis, although they may also be due to the disruptive effects of amniotic band syndrome and occur later in development.

The clinical finding when a lateral cleft is present is termed macrostomia, or widening of the oral commissure. These clefts can be associated with skeletal malformations of the lateral face and external ear including the maxilla, zygomatic bone, and ascending branch of the mandible. This type of cleft is challenging to diagnose on prenatal ultrasound examination, particularly with 2D ultrasound. The widening of the mouth and facial asymmetry are best seen in the coronal view ( Fig. 10-20 ). If such a cleft is suspected, 3D ultrasound in surface mode may be helpful to further elucidate the location and extent of the cleft. Given the frequent involvement of nearby skeletal structures, surgical repair of these types of clefts is a difficult and multistep process.