Treacher Collins syndrome (TCS) is a rare congenital craniofacial disorder, typically inherited as an autosomal dominant condition. Here, we report on a family in which germline mosaicism for TCS was likely present. The proband was diagnosed with TCS based on the typical clinical features and a pathogenic variant TCOF1 (c.4369_4373delAAGAA, p.K1457Efs*12). The mutation was not detected in his parents\' peripheral blood DNA samples, suggesting a de novo mutation had occurred in the proband. However, a year later, the proband\'s mother became pregnant, and the amniotic fluid puncture revealed that the fetus carried the same mutation as the proband. Prenatal ultrasound also indicated a maxillofacial dysplasia with unilateral microtia. The mother then disclosed a previous birth history in which a baby had died of respiratory distress shortly after birth, displaying a TCS-like phenotype. Around the same time, the proband\'s father was diagnosed with mild bilateral conductive hearing loss. Based on array data, we concluded that the father may have had germline mosaicism for TCOF1 mutation. Our findings highlight the importance of considering germline mosaicism in sporadic de novo TCOF1 mutations when providing genetic consulting, and prenatal diagnosis is important when the proband\'s parents become pregnant again.

UNASSIGNED: Treacher Collins syndrome (TCS) is a rare congenital disorder of craniofacial development characterized by numerous developmental anomalies that are restricted to the head and neck. Most TCS cases are inherited in an autosomal dominant manner. The diagnosis of TCS relies on clinical and radiographic findings. The four genes involved in TCS are TCOF1, POLR1D, POLR1C, and POLR1B.
UNASSIGNED: In this report, we present the case of a 7-year-old Moroccan boy who exhibited distinctive dysmorphic features, including coloboma and zygomatic bone hypoplasia. Upon genetic analysis, a mutation in the TCOF1 gene was identified, conclusively confirming the presence of Treacher Collins Syndrome. It is worthy that the correct etiological diagnosis was significantly delayed due to the initial misperception that the observed malformation syndrome was a result of drug teratogenicity.
UNASSIGNED: This case highlights the importance of seeking pharmacovigilance advice if any adverse event occurs following medication use. Furthermore, requesting a genetic consultation to establish a confirmed etiological diagnosis for any malformation syndrome can significantly reduce the protracted social and psychological suffering that patients and their families may endure.

Treacher Collins syndrome (TCS) should be suspected if the triad of micrognathia, glossoptosis, and posterior cleft palate, and deformed external ears are observed during prenatal ultrasonography, excepting Pierre Robin sequence. Visualization of the fetal zygomatic bone and down-slanting palpebral fissures are conducive to differentiation. Molecular genetics testing can establish a definite diagnosis. A 28-year-old pregnant Chinese woman was referred for systematic ultrasound examination at 24 weeks. Two-dimensional and three-dimensional ultrasound showed polyhydramnios, micrognathia, absence of nasal bone, microtia, secondary cleft palate, mandibular hypoplasia, glossoptosis, and normal limbs and vertebrae. Pierre Robin sequence was misdiagnosed with the triad of micrognathia, glossoptosis, and posterior cleft palate. Final diagnosis of TCS was confirmed by whole-exome sequencing. Visualization of the fetal zygomatic bone and down-slanting palpebral fissures can facilitate a differential diagnosis between Pierre Robin sequence and TCS, with the triad of micrognathia, glossoptosis, and posterior cleft palate.

Treacher Collins syndrome (TCS) is a rare genetic disorder that affects craniofacial development due to malformation of the first and second branchial arches. The TCOF1 gene is mainly responsible for this condition. Here, we present a case of a 13-year-old adolescent girl with complaints of maligned teeth with conductive deafness. On clinical examination, she had retrognathia, a broad nose, maligned teeth, a high arch palate, and midfacial hypoplasia. On the basis of the clinical findings, a diagnosis of a mild-variant TCS was made as eyes were not involved and supportive treatment was given to the patient. The symptoms of the disease have a varying range of severity. Early diagnosis and supportive treatments, which include multidisciplinary treatment involving pediatrics, otolaryngologists, audiologists, orthodontists, and psychologists, are very important for the management of such cases.

The purpose of this study is to analyze the clinical characteristics of a Treacher Collins syndrome (TCS) patient carrying a de novo variant of TCOF1, and briefly analyze the correlation between genetic results and clinical features. Also, the pathogenesis and clinical treatment of TCS are reviewed.
A Chinese pedigree with TCS containing 8 members was enrolled. Phenotype of the proband was evaluated by a surgeon, then whole exome sequencing of the proband was performed. Then we verified the proband-derived variants by Sanger sequencing in the pedigree. Correlation between genotype and phenotype was analyzed.
The study was conducted in a stomatological hospital.
A Chinese pedigree with TCS containing 8 members.
To ascertain the genetic variants in the Chinese pedigree with TCS.
Blood samples were collected.
We reported a case of typical TCS with a de novo missense variant (NM_001371623.1:c.38T>G, p.(Leu13Arg)) in exon 1 of TCOF1, who presented asymmetrical facial abnormalities, including downward slanting of the palpebral fissures, sparse eyebrows, lateral tilt of the eyeballs, bilateral external ears deformities, hypoplasia of midface, reduction of the zygomatic body, bilateral orbital invagination, right external auditory canal atresia, mandibular ramus short deformity, cleft palate and the whole face was convex.
This research found a novel variant of TCS in Chinese, expanding the spectrum of TCS pathogenic variants. Genetic results combined with clinical phenotype can make a definite diagnosis and provide genetic counseling for the family.

We report the first case of bilateral hypoglossal nerve stimulator implantation in a patient with Treacher Collins syndrome and very severe obstructive sleep apnea, who was initially intolerant of continuous positive airway pressure (CPAP) treatment. Novel bilateral hypoglossal nerve stimulation in combination with CPAP allowed near obliteration of snoring, improved sleep quality, and ability to maintain the CPAP mask in position in the setting of craniofacial changes associated with this condition.
Wong ACL, Jones A, Stone A, MacKay SG. Combination CPAP and bilateral hypoglossal nerve stimulation for obstructive sleep apnea in Treacher Collins syndrome: first case report. J Clin Sleep Med. 2023;19(1):197-199.

OBJECTIVE: Facial dysostosis is a group of rare craniofacial congenital disabilities requiring multidisciplinary long-term care. This report presents the phenotypic and genotypic information from South India.
METHODS: The study is a case series.
METHODS: This was an international collaborative study involving a tertiary craniofacial clinic and medical genetics unit.
METHODS: The participants were 9 families with 17 affected individuals of facial dysostosis.
METHODS: Exome analysis focused on known genes associated with acrofacial and mandibulofacial syndromes.
METHODS: The outcome measure was to report phenotyptic and genetic heterogeneity in affected individuals.
RESULTS: A Tessier cleft was seen in 7 (41%), lower eyelid coloboma in 12 (65%), ear anomalies in 10 (59%), uniolateral or bilateral aural atresia in 4 (24%), and deafness in 6 (35%). The facial gestalt of Treacher Collins syndrome (TCS) showed extensive phenotypic variations. Pathogenic variants in TCOF1 (Treacher Collins syndrome) were seen in six families, POLR1A (acrofacial dysostosis, Cincinnati type) and EFTUD2 (mandibulofacial dysostosis with microcephaly) in one each. One family (11.1%) had no detectable variation. Five out of six probands with Treacher Collins syndrome had other affected family members (83.3%), including a non-penetrant mother, identified after sequencing.
CONCLUSIONS: Our report illustrates the molecular heterogeneity of mandibulofacial dysostosis in India.

Treacher Collins syndrome (TCS) is the most common mandibulofacial dysostosis with an autosomal dominant or rarely recessive manner of inheritance. It is still challenging to make a definite diagnosis for affected fetuses with TCS only depending on the ultrasound screening. Genetic tests can contribute to the accurate diagnosis for those prenatal cases.
Targeted exome sequencing was performed in a fetus of a Chinese family, who presenting an abnormal facial appearance by prenatal 2D and 3D ultrasound screening, including micrognathia, nasal bridge pit, and abnormal auricle. The result was validated with multiplex ligation-dependent probe amplification (MLPA) and real-time quantitative PCR (qPCR).
A novel 2-6 exons deletion of TCOF1 gene was identified and confirmed by the MLPA and qPCR in the fetus, which was inherited from the affected father with similar facial anomalies.
The heterozygous deletion of 2-6 exons in TCOF1 results in the TCS of this Chinese family. Our findings not only enlarge the spectrum of mutations in TCOF1 gene, but also highlight the values of combination of ultrasound and genetics tests in diagnosis of craniofacial malformation-related diseases during perinatal period.

BACKGROUND: Nager syndrome is a rare genetic syndrome characterized by craniofacial and preaxial limb anomalies. Haploinsufficiency of the SF3B4 gene has been identified as a significant reason for Nager syndrome. Treacher Collins syndrome (TCS) has similar facial features; however, the TCOF1, POLR1D, and POLR1C genes have been reported as the critical disease-causing genes. Similar phenotypes make it easy to misdiagnose.
METHODS: In this report, we have presented a case of one newborn with acrofacial dysostosis, who was first diagnosed with TCS. Expanded next-generation sequencing eventually detected a (c.1A>G) heterozygous mutation in the SF3B4 gene at chr1:149899651 that was confirmed by Sanger sequencing. Combined with his preaxial limb anomalies discovered after his death, a diagnosis of Nager syndrome was made.
CONCLUSIONS: This report presents one patient with Nager syndrome who was initially misdiagnosed with TCS. Correct genetic testing will be beneficial to future prenatal diagnosis.

Treacher Collins syndrome (TCS) is a type of mandibulofacial dysostosis with incomplete penetrance and high intra- and interfamilial clinical heterogeneity, and it is associated with mutations of treacle ribosome biogenesis factor 1 (TCOF1), and RNA polymerase I and III subunit (POLR1)C and POLR1D genes. In the present case report, a patient with TCS with auricle dysplasia and hearing loss accompanied with intellectual disability is described. Sequence analysis was performed on blood samples from the patient and his father via oligonucleotide-based target capture, followed by next-generation sequencing. Alignment and variant calls were generated using the Burrows-Wheeler Aligner and Genome Analysis Toolkit, followed by bioinformatics analysis of the detected variants. A novel heterozygous mutation, c.911C>T (p.Ser304Leu), was detected in the TCOF1 gene, which was inherited from the father. The father of the patient only suffered from hearing loss. The present report is the first to identify an association between phenotypic variability and TCOF1 gene mutations and thus contributes to our understanding of the association between the genotype and phenotype in patients with TCS and offers clinically relevant information for diagnosis of the syndrome.