Mandibulofacial dysostosis is a genetic condition which features multiple phenotypical abnormalities in facial characteristics derived from the first pharyngeal arch. The main malformations include hypoplastic zygomas, an underdeveloped jaw, abnormally large mouth and a downwards-tilting rima palpebrarum, accompanied by a variety of other irregular characteristics.
Mandibulofacial dysostosis can include various types of facial abnormalities and various degrees of severity. Possible symptomatology is broad and involves the following :
Patients exhibit underdeveloped zygomatic bones, sinuses and lower jaw. The eyes are often set wide apart from each other (hyperteloric orbits) and air cells are absent from the mastoids. The cranial base is abnormally curved. The aforementioned defects are observed via radiographic imaging.
The nose seems disproportionately bigger, although its actual size is regular. This is caused by underdeveloped zygomatic bones and supraorbital rims. The longitudinal opening of the eyelids follows a downwards- sloping course and the outer part of the lower lids may also feature a coloboma. A receding lower jaw is also observable. Hearing loss is frequently diagnosed in patients with mandibulofacial dysostosis and is a result of ear deformities. The external part of the ear may be abnormally shaped and, as far as the middle mechanism is concerned, the patient may exhibit meatal atresia, underdeveloped or absent incus and malleus, lack of the middle ear and monopodal stapedes. The development of fistulas connecting the tragus and the outer corner of the mouth are also observed.
Additionally, approximately 30% of patients exhibit a given inability of the soft palate to accomplish palatopharyngeal closure, which leads to a cleft palate. Parotid glands may not be present and the pharynx is markedly underdeveloped.
Mandibulofacial dysostosis is not accompanied by cognitive impairment. However, the frequent and severe hearing loss due to hypoplastic ear particles often lead to a wrongly diagnosed lower intelligence.
Generally, the clinical picture of the disease features fluctuating and diverse symptomatology. Most prominent features are hearing loss of the conductive type, dysphagia due to a cleft palate, problems with vision and a backwards displacement of the tongue.
Ultrasonographic scans conducted as part of the standard obstetrical prenatal care are able to detect facial disfigurement early during the course of pregnancy  . A definitive diagnosis would require genetic testing of parents and fetal cells or amnic fluid, but the procedure has not been applied clinically as of yet.
Postpartum, a newborn must be thoroughly examined, if the physical examination causes suspicion to arise in the direction of mandibulofacial dysostosis. Oxygen saturation should be meticulously monitored, feeding capability must be ensured and tests conducted to diagnose hearing impairment are also mandatory. Postnatal genetic diagnosis may be an invaluable tool in cases of a doubtful diagnosis. The same pertains to craniofacial computerized tomography scans, plain radiographs and a magnetic resonance imaging scan: they can all contribute to the establishing of a definitive diagnosis and the successful assessment of surgical options. Imaging studies include:
Treatment of mandibulofacial dysostosis is symptomatic and individualized .
The first step after diagnoses is to ensure oxygenation sufficiency and assess dysphagic phenomena . A backwards positioning of the mandible can result in substantial airway obstruction; therapeutic measures vary depending on the degree of severity. The newborn may be positioned in a way that enables normal breathing, but if this method fails, intubation and tracheostomy may be mandatory to ensure breathing. Tracheostomy may be required for years before a normal airway can be achieved.
Young individuals who cannot feed receive gavage-mediated feeding or a gastrostomy. Hearing loss should be treated with proper aids, in order to allow for the normal mental development of the child and intrafamilial bonding.
The retropositioning of the tongue, which leads to airway obstruction can also be addressed in a more invasive manner. It is surgically attached to the lip and anterior mandible, do that it is positioned in a more forward location and releases the nasopharynx. Distraction osteogenesis is a procedure that can also be performed in order to lengthen the mandible. Incisions are made to the jaw postpartum and distraction instruments are used to achieve stretching. The process is considered successful when the mandible is stretched 10 millimeters and the instrumentation is removed. Various other surgical solutions are available, depending on the type of deformity, whether they are aesthetic procedures or aim at enhancing functionality.
Mandibulofacial dysostosis is a genetic condition. Various genes have been identified, with TCOF1 being the predominant mutation in over 90% of the patients diagnosed with the disease  . Ribosomal RNA formation is abnormal as a result of the mutation, which leads to a disfigured face, due to impairment of the proteins mediating the formation of the facial skeleton.
The specific pattern of inheritance depends on each individual's mutation. An abnormal TCOF1 or POLR1D gene (the latter being a less frequent mutation leading to the same phenotype) is passed down via an autosomal dominant pathway; this means that at least one parent is already affected by the disease. On the other hand, another mutation to the POLR1C gene is inherited via an autosomal recessive inheritance pattern and means that a child can be born with mandibulofacial dysostosis from two completely unaffected individuals.
Spontaneous mutations have also been observed; in fact, the majority of patients are descended from families with no other diseased member.
Mandibulofacial dysostosis affects 0.5 to 1 per 50,000 live births  and is usually detected postnatally. Embryos that are severely disfigured may be diagnosed during pregnancy with the aid of an ultrasonographic evaluation. Newborns with insignificant symptomatology may be diagnosed later in life, when the development of facial features makes abnormalities more prominent.
Mandibulofacial dysostosis is a result of various mutations to the TFCO1, POLR1D and POLR1C genes. Over 90% of the patients exhibit mutations related to the TFCO1 genetic location, a mutation that is passed down to a person's offspring via an autosomal dominant pattern of inheritance; penetrance is almost always 100%. The majority of the cases, however, develop the disease as a result of a spontaneous mutation to the aforementioned genes.
The genetic location of the most clinically significant gene, TFCO1, is on chromosome 5. As of yet, 50 distinct mutations have been documented, including deletions, insertions and splicing mutations. The particular genetic locus is responsible for the regulation of the production of the treacle protein; the latter is itself responsible for the formation and shaping of the facial skeleton. The molecular pathophysiologic mechanism is believed to encompass a given haploinsufficiency, due to the premature insertion of termination codons in the reading frame  .
The condition cannot be prevented, as it is either inherited or a result of a spontaneous mutation. Genetic counseling is mandatory to parents descended from families with a history of the disease.
Mandibulofacial dysostosis (MFD) is a condition also known as Treacher-Collins syndrome and is inherited primarily via an autosomal dominant inheritance pattern. The first gene ever to be detected for this condition is the TCOF1 gene, responsible for the production of the nucleolar phosphoprotein Treacle . A plethora of other genetic mutations has since been documented, which are extremely particular to the members of each family. The 5th chromosome is invariably implicated in the mutation process, according to genetic mapping carried out in many families with the condition and relatively small deleted regions can lead to the MFD syndrome.
However, more than half of the patients diagnosed with the disease are born into families with no prior medical history of mandibulofacial dysostosis, a fact which delineates the possibility of spontaneous mutations as well. The syndrome is characterized by extreme symptom variability: even though the penetrance of the abnormal gene is believed to be increased, there are family members who carry the mutation and display minimal symptomatology, even non-observable one. On the other hand, the mutation may be so intensely expressed in other newborns, that perinatal death might occur. The fluctuating clinical picture and characteristics associated with the disease indicate that not only genetics, but environmental factors and random variables play a significant role to each individual's phenotype .
Mandibulofacial dysostosis, otherwise known as Treacher Collins syndrome, is a congenital condition which leads to disfigured facial characteristics.
The disease is a result of genetic mutation. The gene that is most commonly involved is the TFCO1 gene on chromosome 5 and over 50 mutations have been tracked until now. This gene is responsible for the production of a protein, without which, facial characteristics cannot fully form. Mandibulofacial dysostosis most of the times occurs spontaneously, without any genetic family background (60% of the cases); in the rest of the cases it is inherited from the parents. There are two possible ways to inherit a defective gene: the autosomal recessive pattern and the autosomal dominant pattern. In cases of autosomal dominant inheritance, a parent is already affected by the condition and is they pass one defective gene to their offspring, the latter will also develop the disease. In the pattern of inheritance is the autosomal recessive one, both parents can be normal, but if they both carry a mutated gene and they both pass it down to their offspring, the child will be born with mandibulofacial dysostosis.
Most symptoms are observed simply with the eye and include underdeveloped cheek bones, abnormal ears, an opening in the roof of the mouth (cleft palate), eyes at an abnormally long distance from each other and a very small lower jaw. Sometimes the tongue is positioned backwards in the mouth; this feature alongside the small jaw may result in the obstruction of the airway. People with mandibulofacial dysostosis have normal intelligence but may have significant hearing loss.
The condition can be detected before birth. Chorionic villous sampling, amniocentesis and an ultrasonographic scan can help to diagnose the disease. After birth, a physical examination will reveal facial characteristics which are compatible with the syndrome.
Therapy is designed depending on the particular symptoms of each patient. Breathing problems are treated with a more convenient positioning of the newborn, with a tracheostomy or a surgical procedure which pulls the tongue forward, so that the airway is free. Hearing aids are used to restore hearing to a considerable degree and the cleft palate can also be surgically mended. Psychological support is of vital importance both to the children and their families.