Treacher Collins syndrome by A.Griguolo

Generality

Treacher Collins syndrome is a rare genetic disorder that causes particular deformities and facial abnormalities.

Due to the mutation of one of the genes known as TCOF1, POLR1C and POLR1D, Treacher Collins syndrome can be both a condition acquired during embryonic development and a hereditary condition.

The symptoms and signs of Treacher Collins syndrome are found, in part, already at birth, which favors early diagnosis.

Currently, unfortunately, those who suffer from Treacher Collins syndrome can only rely on symptomatic treatments - that is, aimed at alleviating the symptoms - as there is no cure capable of canceling the consequences of the mutation against the 3 genes mentioned above.

What is Treacher Collins Syndrome?

Treacher Collins syndrome is a genetic disease that, by altering the normal development of the bones and soft tissues making up the face, determines a number of characteristic facial deformities in its carriers.

Epidemiology

According to statistics, an individual every 50, 000 would be born with Treacher Collins syndrome.

Treacher Collins syndrome is therefore included in the list of so-called rare genetic diseases .

Origin of the name

Treacher Collins syndrome owes its name to Edward Treacher Collins, the British surgeon and ophthalmologist who, around 1900, described it for the first time in a detailed and in-depth manner.

Causes

The cause of Treacher Collins syndrome is the mutation (that is, an anomaly in the normal DNA sequence) of one of the human genes known as TCOF1, POLR1C and POLR1D .

In other words, an individual suffers from Treacher Collins syndrome, when one of the genes TCOF1, POLR1C and POLR1D has an abnormality in the DNA sequence.

Genes implicated in Treacher Collins syndrome: site and normal function

Premise: the genes present on human chromosomes are DNA sequences that have the task of producing fundamental proteins in biologic processes indispensable to life, including cell growth and replication.

The TCOF1, POLR1C and POLR1D genes reside, respectively, on chromosome 5, on chromosome 6 and on chromosome 13 .

In the absence of mutations against them (when in a person not affected by Treacher Collins syndrome), the aforementioned genes each produce a protein with a key role in the correct development of bones and soft tissues of the face; more specifically, they produce proteins responsible for the production of a ribosomal RNA (a particular type of RNA), which serves to regulate the growth processes of bones and soft tissues of the face.

What causes the mutation of Treacher Collins syndrome genes?

In the presence of mutations responsible for Treacher Collins syndrome, the TCOF1, POLR1C and POLR1D genes lose the ability to express functional proteins, which leads to the absence of guiding elements during bone and soft tissue development processes in the face.

In other words, the genetic mutations at the origin of Treacher Collins syndrome cause the absence of agents responsible for regulating the right growth of bone tissues and soft tissues that make up the human face.

Hereditary or acquired disease?

Treacher Collins syndrome can be the result of either a hereditary mutation (ie transmitted via parental means) or a spontaneously acquired mutation, from nothing and without precise reasons, during embryonic development (ie after the spermatozoon has fertilized the egg and embryogenesis began).

Statistically speaking, Treacher Collins syndrome is more often an acquired condition than an inherited condition; in fact, it is related to an acquired type mutation, in 60% of clinical cases, and to a hereditary mutation, in the remaining 40% (*)

* NB: the statistical data in question relate exclusively to the cases of Treacher Collins syndrome due to the mutation of the TCOF1 and POLR1D genes.

For the clinical cases associated with the mutation of the POLR1C gene, there is no information on the type of mutation.

Inheritance in Treacher Collins syndrome

To understand…

Each human gene is present in two copies, called alleles, one of maternal origin and one of paternal origin.
A genetic disease is autosomal dominant when the mutation of only one copy of the gene that causes it is sufficient to manifest itself.
An inherited disease is autosomal recessive when mutation of both copies of the gene that causes it is required to occur.

Treacher Collins syndrome due to the mutation of the TCOF1 and POLR1D genes has all the characteristics of an autosomal dominant disease ; in contrast, Treacher Collins syndrome related to the POLR1C gene mutation has the genetic characteristics typical of an autosomal recessive disease .

Symptoms and Complications

The symptoms and signs of Treacher Collins syndrome vary in severity from patient to patient. This is due to the fact that, for reasons still unclear, Treacher Collins syndrome is responsible for severe consequences, in someone, and minor consequences, in someone else.

It is important to remind readers that the symptomatic picture that can be observed in the presence of Treacher Collins syndrome depends mainly on the lack of proper development of the bones and soft tissues of the face.

The manifestations of Treacher Collins syndrome: the details

Going into the details of the symptomatology, Treacher Collins syndrome is typically due to:

Small jaw and small chin (together, these two anomalies constitute the so-called micrognathia );

Undeveloped cheekbones;
Ocular anomalies of various kinds, including:

Eyes directed downwards;
Coloboma of the lower eyelid (partial or total absence of skin tissue constituting the lower eyelid);
Upper and lower palpebral ptosis;
Unusual narrowing of the tear ducts;
No eyelashes on the lower eyelid.

Ears absent, small or deformed, and abnormal development of the ear canal;

Other possible symptoms

Sometimes, Treacher Collins syndrome can further enrich the classic pattern of symptoms and signs reported above by causing:

Brachicefalia;
Dental deformities, such as:

Dental agenesis (lack of one or more teeth);
Teeth with opaque enamel;
Poor positioning of the maxillary first molars;
Teeth excessively spaced apart (dental diastema).

Macrostomia (anomalous enlargement of the mouth opening);
cleft palate;
Ocular hypertelorism (eyes too far apart);
Heart defects;
Nasal deformities;
Unusual hairline at ear level.

What happens in the most serious cases?

When Treacher Collins syndrome is particularly severe, it happens that:

Defects in the cheekbone, jaw and chin, and dental deformities are so severe that they induce respiratory problems, dental malocclusion and chewing disorders;
The anomalies at the level of the ears are so deep as to cause hearing deficits and, consequently, language problems;
The nasal deformities are so marked that the patient suffers from coanal atresia and sleep apnea syndrome, and develops further respiratory problems;
The ocular anomalies are so pronounced that the patient suffers from a loss of sight (due to refractive defects), strabismus and anisometropia (it is when the eyes present a different refraction).

Does Treacher Collins syndrome affect intelligence?

Usually, Treacher Collins syndrome has no effect on the intellectual development of the affected person; in other words, those who suffer from Treacher Collins syndrome usually have normal intelligence.

Did you know that ...

According to statistics, Treacher Collins syndrome is associated with intellectual problems in a small 5% of clinical cases (therefore, in 95% of cases it is related to a completely normal intelligence).

Psychological complications

Because of the facial deformities with which it is destined to coexist, the patient of Treacher Collins syndrome tends to develop, especially during adolescence and at a more mature age, psychological problems ( depression, low mood, social phobia, etc.), which they compromise the insertion in a social context and, more generally, the whole quality of life .

Diagnosis

To make the diagnosis of Treacher Collins syndrome, information from:

The anamnesis ;
The objective examination ;
A genetic test .

Sometimes, these assessments are followed by a series of radiological examinations (eg, CT and X-ray) with the aim of further enriching the picture of previously collected clinical data.

Anamnesis and physical examination

Anamnesis and physical examination consist essentially in an accurate evaluation of the symptomatology exhibited by the patient.

In a context of Treacher Collins syndrome, it is in these phases of the diagnostic procedure that the doctor verifies the presence of the various facial anomalies and of any problems related to these (respiratory disorders, chewing disorders, dental malocclusion, visual anomalies, etc.) .

Genetic test

It is the DNA analysis aimed at detecting mutations of critical genes.

In a context of Treacher Collins syndrome, it represents the confirmation diagnostic test, as it allows to highlight the mutation of one of TCOF1, POLR1C and POLR1D.

Radiological examinations

In a context of Treacher Collins syndrome, radiological examinations may have, as an object of interest, the dental structure and the anatomy of the ear canal.

Their realization is indicated, above all, when the present genetic condition has caused serious deformations of the teeth and / or severe hearing deficits. The images, in fact, coming from a CT scan of the ear canal or X-rays to the dental arches are of enormous help when planning a therapy against the aforementioned dental deformations and the aforementioned hearing deficits.

When is the diagnosis made? Is prenatal diagnosis possible?

Treacher Collins syndrome can be diagnosed early in life. Clearly, such an early diagnosis is easier for an experienced doctor or when there is a suspicion that the unborn child may be the carrier of the condition in question.

Amniocentesis

PRENATAL DIAGNOSIS

Prenatal diagnosis of Treacher Collins syndrome is only possible through a prenatal genetic test, performed on a sample of amniotic fluid (ie after amniocentesis ) or chorionic villi (therefore after a villocentesis ).

Curiosity

In the prenatal phase, Treacher Collins syndrome is diagnosed by ultrasound only in the final stages of pregnancy and when the facial abnormalities are very severe.

Therapy

The treatment of Treacher Collins syndrome is purely symptomatic - that is aimed at controlling the symptomatology and avoiding / postponing complications - as there is still no cure capable of canceling, before birth, the mutation responsible for the disease in question.

Symptomatic therapy: what does it consist of?

Based on the magnitude and severity of the facial abnormalities (and their consequences), the symptomatic treatment of Treacher Collins syndrome may include:

A therapeutic plan that contrasts respiratory problems. For example, in the case of very small patients, a therapeutic plan with the aforementioned purposes could include tracheostomy or the use of particular positions designed to promote breathing.
A series of maxillofacial surgery interventions aimed at solving or improving problems, such as micrognathia, cleft palate, little developed cheekbones, nasal deformities, deformed ears, the presence of an inadequate ear canal, dental anomalies etc.
Often, these interventions are for reconstructive purposes.
The use of hearing aids to provide non-invasive solutions to acoustic deficits.
The use of corrective glasses (if, of course, there are sight problems).
Speech therapy (or speech therapy ), where acoustic deficits have compromised language control.
Psychotherapy, in order to counteract any problems of depression, social phobia, etc.

IN WHICH PHASES OF LIFE WOULD YOU SEE IN MAXILLO-FACIAL SURGERY?

Due to the various facial malformations induced by Treacher Collins syndrome, there is a more suitable moment than others for practicing maxillofacial surgery.

For example, cleft palate surgery should take place around 9-12 months of life; micrognathic surgery at 13-16 years, if the malformation is mild or moderate, or 6-10 years, if the malformation is severe; nasal reconstruction surgery at 18 years; reconstruction of the cheekbones at 5-7 years; and so on.

What medical figures involve symptomatic therapy of Treacher Collins syndrome?

The symptomatic treatment of Treacher Collins syndrome requires the coordinated intervention of several medical specialists, including: pediatricians, geneticists, speech therapists, maxillofacial surgeons, ophthalmologists, dentists and psychiatrists.

Prognosis

If it does not cause particularly severe facial malformations, Treacher Collins syndrome is associated with a normal life expectancy and a discreet quality of life; on the other hand, if it is responsible for severe facial deformities, it can seriously compromise the health of those who strike (respiratory problems can even be fatal) and be a profound obstacle to a minimally satisfying life.