Treacher Collins Syndrome (TCS) is a rare genetic disorder that affects the development of bones and tissues in the face. Also known as mandibulofacial dysostosis, it is characterized by distinctive symmetrical craniofacial malformations. The severity of features varies widely among affected individuals, ranging from very mild to severe. Diagnosis moves from initial clinical suspicion to definitive molecular confirmation.
Recognizing Clinical Indicators
Diagnosis begins with recognizing the characteristic physical features. A clinician suspects TCS upon observing the unique facial presentation, which results from the underdevelopment of specific facial bones. Noticeable features include hypoplasia (underdevelopment) of the cheekbones, causing a flattened mid-face appearance. The lower jaw (mandible) is also typically underdeveloped, a condition known as micrognathia. This small jaw can sometimes lead to difficulties with breathing and feeding immediately after birth.
Ear anomalies are another prominent sign, presenting as small, malformed, or entirely absent external ears (microtia or anotia). The eyes often have a downward slant, and a notch in the lower eyelid, known as a coloboma, along with sparse or absent lower lid eyelashes, is frequently present.
Prenatal Detection Methods
Diagnosis can sometimes begin before birth through specialized imaging techniques. Detailed Level II or Level III prenatal ultrasounds are used to visualize the fetal craniofacial structures. These scans often reveal primary indicators of TCS, such as micrognathia and mandibular hypoplasia, appearing as a small or retracted lower jaw on the profile view. Visualization of the fetal zygomatic bone and the downward slant of the eyes further raises suspicion.
Because anomalies may be subtle in early gestation, prenatal detection often occurs later in the second or third trimester. The presence of polyhydramnios (excessive amniotic fluid) may also be noted, as structural issues can impair the fetus’s ability to swallow properly. If strong suspicion arises, especially with a known family history, definitive prenatal diagnosis is sought through invasive procedures. Chorionic villus sampling (CVS) or amniocentesis collect fetal cells, which are then subjected to genetic analysis to check for specific gene mutations associated with TCS.
Confirmatory Postnatal Evaluation
If not diagnosed prenatally, the characteristic features usually lead to a clinical diagnosis soon after birth. A physical examination by specialists is followed by structural imaging to confirm the extent of bone malformations. Computed Tomography (CT) scans are a primary tool, providing detailed, three-dimensional views of the skeletal structures. CT imaging is useful for visualizing the temporal bones, cheekbones, and the internal structure of the ears. This imaging identifies hypoplasia of the zygomatic arches and middle ear abnormalities, such as malformed or absent ossicles, the tiny bones responsible for sound conduction.
A comprehensive audiological evaluation is an immediate necessity, as conductive hearing impairment is a near-universal feature. Specialized hearing tests, such as Auditory Brainstem Response (ABR) or Otoacoustic Emissions (OAE), assess how well sound travels through the outer and middle ear. This conductive hearing loss is caused by structural issues in the ear canal and middle ear cavity. The combination of clinical observation and detailed structural imaging strongly suggests the diagnosis and guides the multidisciplinary management plan.
Molecular Confirmation via Genetic Testing
While clinical signs and imaging provide a strong indication, definitive confirmation relies on molecular genetic testing. This involves analyzing a patient’s DNA to identify a pathogenic mutation in one of the known causative genes. The majority of cases (80 to 90 percent) are linked to a mutation in the TCOF1 gene. Less frequently, the syndrome is caused by mutations in the POLR1C or POLR1D genes.
Genetic sequencing, often through a targeted gene panel or whole-exome sequencing, pinpoints these specific mutations in a blood sample. A TCOF1 mutation usually follows an autosomal dominant inheritance pattern, meaning only one copy of the altered gene is needed for the condition. The less common POLR1C gene mutation results in an autosomal recessive form, requiring mutations in both copies of the gene. Identifying the specific mutated gene provides the molecular proof required for a conclusive diagnosis. This genetic information is essential for counseling, allowing specialists to discuss recurrence risk and inheritance patterns.