Overview of Congenital Craniofacial Anomalies

Congenital anomalies may be classified as

• Deformities

• Malformations

A deformity is an alteration in shape due to unusual pressure and/or positioning in utero (eg, a depressed nasal tip, an over-folded ear) or after birth (eg, positional plagiocephaly—head flattening due to prolonged lying in one position). Deformities are present in about 2% of births; some resolve spontaneously within a few days, but others persist and require treatment.

A malformation is an error in normal organ or tissue development. Causes include chromosomal abnormalities, single-gene defects, teratogenic agents, or a combination of genetic and environmental factors; a decreasing number of cases are considered idiopathic. Congenital malformations are present in about 3 to 5% of births. A clinical geneticist should assess affected patients to establish a definitive diagnosis, which is essential for formulating an optimal treatment plan, providing anticipatory guidance and genetic counseling, and identifying relatives at risk of similar abnormalities.

Many craniofacial anomalies result from malformation of the first and second pharyngeal arches (also referred to as visceral or branchial arches), which are embryologic structures that develop into the skull, face, ears, and neck.

The pharyngeal arches are a series of paired bulges along the lateral head and neck region of the embryo. Each arch contains a core derived from mesoderm and neural crest cells and is lined internally by endoderm and externally by ectoderm (1). The first pharyngeal arch (mandibular arch) develops into the maxilla, mandible, malleus, and incus and into the muscles of mastication and the trigeminal nerve (5th cranial nerve). The second pharyngeal arch (hyoid arch) develops into the stapes, styloid process, and part of the hyoid bone and into the muscles of facial expression and the facial nerve (7th cranial nerve).

Each of the specific congenital anomalies discussed here typically can be associated with many different genetic syndromes, some of which are named (eg, Treacher Collins syndrome). Because of the large number of syndromes, the topics here are focused on the different structural manifestations. Detailed information on many of the specific syndromes is available from the Online Mendelian Inheritance in Man (OMIM) catalog of genetic disorders.

The anomalies discussed are

• Cleft palate and cleft lip

• Craniosynostosis

• Ear anomalies

• Eye anomalies

• Jaw anomalies

• Macrocephaly

• Microcephaly

In general, children with congenital craniofacial anomalies should be evaluated for other associated congenital anomalies and developmental delays that may require treatment, extra support, or both. Identification of the underlying syndrome is important for prognosis and family counseling; a clinical geneticist, when available, can help guide the evaluation and should evaluate affected patients even in cases of an apparent isolated congenital anomaly.

Chromosomal microarray analysis, specific gene tests, or broader gene panel tests should be considered in the evaluation of patients with congenital craniofacial anomalies. If the results of these tests are nondiagnostic, whole exome sequencing analysis may be recommended.