Clinical characteristics: Treacher Collins syndrome (TCS) is characterized by bilateral and symmetric downslanting palpebral fissures, malar hypoplasia, micrognathia, and external ear abnormalities. Hypoplasia of the zygomatic bones and mandible can cause significant feeding and respiratory difficulties. About 40%-50% of individuals have conductive hearing loss attributed most commonly to malformation of the ossicles and hypoplasia of the middle ear cavities. Inner ear structures tend to be normal. Other, less common abnormalities include cleft palate and unilateral or bilateral choanal stenosis or atresia. Typically intellect is normal.
Diagnosis/testing: The diagnosis of TCS is established in about 97% of probands by detection of a heterozygous (autosomal dominant) pathogenic variant in TCOF1, POLR1D, or POLR1B or biallelic (autosomal recessive) pathogenic variants in POLR1C or POLR1D using molecular genetic testing and in about 3% of probands by clinical findings when molecular genetic testing has not been performed or does not identify pathogenic variants in one of the known genes.
Management: Treatment of manifestations: Treatment should be tailored to the specific needs of each individual, preferably by a multidisciplinary craniofacial management team. Neonates with airway issues may require special positioning or tracheostomy to facilitate ventilation. Hearing loss is treated with bone conduction amplification, speech therapy, and educational intervention. Craniofacial reconstruction is often necessary. Cleft palate repair (if needed) occurs at about age one year; zygomatic and orbital reconstruction at about age five to seven years; and bilateral microtia and/or narrow ear canal reconstruction after age six years. The age of maxillomandibular reconstruction varies by severity; orthognathic therapies are typically before age 16 years.
Genetic counseling: Treacher Collins syndrome (TCS) can be inherited in an autosomal dominant or autosomal recessive manner.
Autosomal dominant TCS. About 55%-61% of probands have the disorder as the result of a de novo TCOF1, POLR1D, or POLR1B pathogenic variant. Each child of an individual with TCS has a 50% chance of inheriting the pathogenic variant.
Autosomal recessive TCS. The parents of a child with autosomal recessive TCS are obligate heterozygotes (i.e., carriers of one POLR1C or POLR1D pathogenic variant). At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
Once the TCS-related pathogenic variant(s) have been identified in an affected family member, prenatal and preimplantation genetic testing are possible.
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