Treacher Collins and BOR Syndromes

Definition and epidemiology

Treacher Collins syndrome (mandibulofacial dysostosis) is an inherited craniofacial syndrome defined by bilateral, usually symmetrical, underdevelopment of facial structures derived from the first and second pharyngeal arches. Its prevalence is reported as 1 in 50,000 to 1 in 80,000 (Barbosa et al., 2024; Marszałek-Kruk et al., 2021). Intelligence is usually normal, so early recognition of hearing loss is decisive for the child reaching their developmental potential.

Branchio-oto-renal (BOR) spectrum disorder is an autosomal dominant condition with varying combinations of second pharyngeal arch anomalies (neck fistulae or cysts), preauricular pits, pinna anomalies, hearing loss and kidney and urinary tract anomalies. The form without renal involvement is also called branchio-otic (BO) syndrome. There are no large-scale prevalence data (Smith and Azaiez, 2025).

The clinical diagnosis of BOR rests on major and minor criteria. Major criteria are second arch anomalies, preauricular pits, pinna anomalies, hearing loss and kidney-urinary tract anomalies; minor criteria are preauricular tags, outer, middle and inner ear anomalies, mild facial asymmetry and a cleft or high-arched palate. Three major criteria, two major and two minor criteria, or one major criterion with an affected first-degree relative establish the diagnosis (Smith and Azaiez, 2025).

Symptoms and signs

Typical features of Treacher Collins are downslanting palpebral fissures, a notch in the lower eyelid (coloboma) with missing lashes, underdeveloped cheekbones and lower jaw (micrognathia), cleft palate and pinna anomalies. Canal atresia and microtia occur in 30-75% of cases; the reported frequency of conductive hearing loss ranges from 40-50% to 83-92% depending on the source (Barbosa et al., 2024; Marszałek-Kruk et al., 2021). Features can vary widely even within a family, and a mildly affected parent may never have been diagnosed.

The airway is the main concern in the newborn period. Choanal atresia or stenosis, severe micrognathia and a backward-falling tongue (glossoptosis) can obstruct breathing; some babies need special airway procedures or a tracheostomy at birth, and neonatal intubation or tracheostomy has been reported in 12-18% (Barbosa et al., 2024; Marszałek-Kruk et al., 2021). Obstructive sleep apnoea and feeding difficulties are also common.

In BOR, hearing loss occurs in more than 90% of individuals; it may be mixed (52%), conductive (33%) or sensorineural (29%) and ranges from mild to profound. Preauricular pits are reported in 82%, second arch fistulae or cysts in about 50% and canal atresia or stenosis in 29%. The loss is non-progressive in about 70% and progressive in about 30%, with progression linked to an enlarged vestibular aqueduct (Smith and Azaiez, 2025).

Causes and risk factors

About 60-90% of Treacher Collins cases are caused by a heterozygous variant in TCOF1. Less often POLR1D (6-8%; autosomal dominant or recessive), POLR1B (1-2%; dominant) or POLR1C (about 1%; recessive) is involved (Barbosa et al., 2024). POLR1C and POLR1D encode subunits of RNA polymerases I and III, and their role in the syndrome was shown in 2011 (Dauwerse et al., 2011). What these genes share is ribosome production; its disruption depletes the neural crest cells that would form the facial skeleton early in development. Around 60% of cases arise from a new (de novo) variant with no family history (Marszałek-Kruk et al., 2021).

In BOR the most commonly involved gene is EYA1 (40-52%); SIX1 accounts for 4-35%, and no cause is found in 15-45%. Around one in five EYA1 variants is detected only by deletion/duplication analysis, and SIX5, proposed earlier, is no longer regarded as a BOR gene (Smith and Azaiez, 2025). Inheritance is autosomal dominant with highly variable expressivity: in one family a person may have only a preauricular pit while a relative has severe hearing loss and kidney failure.

The main differential diagnosis is oculo-auriculo-vertebral spectrum (Goldenhar syndrome), in which facial and ear findings are usually asymmetrical and unilateral. For detailed grading of ear anomalies and surgical options, see aural atresia and microtia.

Audiological and clinical assessment

In both syndromes, diagnostic ABR after the newborn hearing screen is the key step. Because canal atresia is common in Treacher Collins, cochlear function is shown with bone conduction ABR; OAEs and tympanometry cannot be recorded in an atretic ear. In BOR the type of loss can differ between ears, so air and bone conduction thresholds must be established for each ear separately.

• Pure-tone audiometry and ABR in Treacher Collins: usually a bilateral conductive loss caused by malformed, fixed or absent ossicles and an underdeveloped middle ear space; the inner ear is usually normal (Barbosa et al., 2024).
• Pure-tone audiometry in BOR: mixed loss is common, and bone conduction thresholds may also be raised. Where the canal is open, tympanometry and acoustic reflexes may point to an ossicular anomaly.
• Imaging (BOR): if hearing fluctuates or progresses, temporal bone CT and/or MRI is used to assess the vestibular aqueduct. Offset cochlear turns (an ‘unwound’ cochlea) are considered diagnostic of EYA1-related BOR; cochlear hypoplasia, an enlarged vestibular aqueduct and hypoplasia of the horizontal semicircular canal may also be seen (Smith and Azaiez, 2025).
• Renal screening (BOR): renal ultrasound, blood urea nitrogen and creatinine, and urinalysis; further imaging if needed; where a kidney or urinary tract anomaly is found, kidney function is reviewed at least once a year (Smith and Azaiez, 2025).
• Airway (Treacher Collins): obstructive sleep apnoea is asked about at each visit and a sleep study is arranged if suspected (Barbosa et al., 2024).
• Genetic testing: TCOF1, POLR1B, POLR1C and POLR1D; in BOR, sequencing plus deletion/duplication analysis of EYA1 and SIX1.

For follow-up, an annual audiological review is recommended in Treacher Collins (Barbosa et al., 2024). In BOR, hearing can progress, so audiometry should be done at every visit, and children with an enlarged vestibular aqueduct should also be counselled about enlarged vestibular aqueduct (Smith and Azaiez, 2025).

Treatment and audiological rehabilitation

In Treacher Collins, bone conduction amplification, speech therapy and educational support are recommended from birth to two years, and bone conduction implants are an option (Barbosa et al., 2024). In young children the bone conduction aid is worn on a softband; implanted systems can be considered after five years, and the implant site is chosen with the plastic surgeon so that it does not compromise a later pinna reconstruction (Zhang et al., 2019). Air conduction hearing aids are often unsuitable because of canal or middle ear anomalies.

Pinna reconstruction should be done after six years of age and before canal and middle ear surgery; canal and middle ear reconstruction is considered for bilateral microtia and/or narrow canals (Barbosa et al., 2024). Cleft palate repair is usually planned at one to two years, and cheekbone and orbital reconstruction at around five to seven years. Severe cases may need a tracheostomy or lengthening of the lower jaw (mandibular distraction) for the airway (Marszałek-Kruk et al., 2021). Given the anaesthetic and airway challenges, hearing procedures may be combined with other operations; the decision rests with the physician.

In BOR, management depends on the type and degree of loss. Air conduction hearing aids are fitted for mild to moderate sensorineural or mixed loss; bone conduction devices are considered when there is canal atresia or stenosis. A cochlear implant (CI) is an option for bilateral severe to profound loss; inner ear malformations do not exclude candidacy but require preoperative imaging and planning, and cochlear nerve aplasia is a contraindication (Smith and Azaiez, 2025). Avoiding loud sound, especially long listening at high levels through in-ear earphones, is advised. Kidney follow-up is led by a nephrologist, and neck fistulae and cysts are managed by a surgeon.

Impact on quality of life and advice

Children with Treacher Collins usually have normal intelligence; if hearing loss is missed, delayed speech can be misread as a cognitive problem. Wearing the device all day, regular speech and language therapy and a remote microphone system at school are therefore important. Visible facial difference can lead to bullying and low self-esteem; psychological support and regular contact between the family and the craniofacial team help.

BOR needs lifelong follow-up: hearing loss may progress and kidney function may decline over time. With autosomal dominant inheritance each child of an affected person has a 50% chance of inheriting the variant, but because expressivity varies, how severely a child will be affected cannot be predicted. Examining siblings and parents, with audiometry and renal ultrasound, identifies mildly affected relatives.

In both syndromes genetic counselling helps families understand their options for future pregnancies. Monitoring daily device use, keeping hearing aids or bone conduction systems well maintained and working with the school on the listening environment are the everyday steps that shape long-term outcomes.