Generality
Apert syndrome is a genetic disorder responsible for a form of craniosynostosis called brachycephaly and a malformation of the fingers and toes called syndactyly.
Observable in a newborn every 68, 000-88, 000, Apert syndrome is due to the specific mutation of the FGFR2 gene, which has the task of regulating the fusion of cranial sutures and the development of fingers and toes.
For the diagnosis of Apert syndrome, physical examination, history, radiological evaluation of the skull and fingers and toes, and, finally, a genetic test are essential.
Currently, those who suffer from Apert syndrome can only rely on symptomatic treatments, that is to say that they alleviate the symptoms and avoid the most serious complications.
Brief review of cranial sutures and their fusion
The cranial sutures are the fibrous joints, which serve to fuse together the bones of the cranial vault (ie the frontal, temporal, parietal and occipital bones).
In normal conditions, the process of fusion of the cranial sutures takes place in the post-natal period, beginning at 1-2 years of age, for some articular elements, and ending at the threshold of 20 years, for others. This long and rhythmic fusion process allows the brain to grow and develop properly.
What is Apert Syndrome?
Apert syndrome is one of the most important genetic diseases that cause craniostenosis (or craniosynostosis ), ie the premature fusion of so-called cranial sutures.
The Apert syndrome, however, owes its notoriety not only to its association with craniostenosis, but also to the fact of being related to a certain degree of syndactyly, that is the congenital anomaly characterized by the fusion of one or more fingers of the hands or of the feet.
The possibility of provoking craniostenosis and syndactyly at the same time makes Apert syndrome an example of acrocephalosyndactyly ; in medicine, an acrocephalosyndactyly is a genetic condition that combines specific malformations of the skull ("acrocephalus" means "pointed head") to the fusion of one or more fingers or toes.
What are the consequences of an early fusion of cranial sutures?
If, as in the case of Apert syndrome and other related diseases, the fusion of the cranial sutures occurs during the prenatal, perinatal (*) or early infancy, encephalic organs such as the brain, the cerebellum and the brainstem, and organs of sense as the eyes undergo alterations both in growth and in form.
* NB: "perinatal life" means the period between the 27th week of gestation and the first 28 days following the birth.
Epidemiology: how common is Apert syndrome?
According to statistics, an individual every 65, 000-88, 000 would be born with Apert syndrome.
Did you know that ...
Genetic diseases that, like Apert syndrome, cause craniosynostoses are around 150.
Among these, in addition to Apert syndrome, stand out for importance: Crouzon syndrome, Pfeiffer syndrome and Saethre-Chotzen syndrome .
Causes
Apert syndrome is due to a specific mutation in the FGFR2 gene, located on chromosome 10 .
In most cases, the aforementioned mutation is acquired completely spontaneously and without precise reasons during embryonic development - that is, after the sperm has fertilized the egg and embryogenesis has begun; more rarely, it is hereditary - that is, transmitted by one or both parents.
Curiosity
The acquired mutation that causes Apert syndrome is an example of " de novo mutation ", that is of "a new mutation completely devoid of a hereditary nature".
What causes the mutation of the gene associated with Apert syndrome?
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.
When it is free of mutations (therefore in a healthy person), the FGFR2 gene implicated in Apert syndrome produces in the right quantities a receptor protein, called Fibroblast Growth Factor Receptor 2, which is essential to mark the melting times of cranial sutures and to control the separation of the fingers and toes (in other words, it signals when the appropriate time is for the fusion of the cranial sutures and regulates the formation of the fingers and toes).
When instead it undergoes the mutation observed in the presence of Apert syndrome, the FGFR2 gene is hyperactive and produces the aforementioned receptor protein in such massive quantities, that the timing related to the fusion of the cranial sutures is altered (it is faster) and the separation processes of the fingers and toes do not occur correctly.
Who is most at risk?
Regarding the acquired cases of Apert syndrome, the factors that induce the mutation of the FGFR2 gene after conception have not been completely clear at the moment.
Research on this aspect is still ongoing.
Apert syndrome is an autosomal dominant disease
To understand...
Each human gene is present in two copies, called alleles, one of maternal origin and one of paternal origin.
Apert syndrome has all the characteristics of an autosomal dominant disease .
A genetic disease is autosomal dominant when the mutation of only one copy of the gene that causes it is sufficient to manifest itself.
Symptoms and Complications
As stated in the beginning, Apert syndrome is associated with two clinical signs: craniostenosis (or craniosynostosis) and syndactyly.
craniostenosis
There are different types of craniosynostosis; to distinguish the various types is or are the cranial sutures subject to premature fusion.
In the case of Apert syndrome, the type of craniostenosis normally present is called brachycephaly . Also known as coronal craniosynostosis, brachycephaly is the cranial anomaly resulting from the early fusion of the coronal sutures, ie the cranial sutures that run between the frontal bone and the parietal bones (it is advisable to consult the figure of the cranial sutures).
The occurrence of the phenomenon of brachycephaly has the following effects:
- Failure to expand the skull forward and backward, which in turn leads to the abnormal growth of the brain in a lateral and upward direction;
- Development of a high and prominent forehead, and a flat back of the skull. The general appearance of the head of an individual with Apert syndrome is that of a long head, developed vertically;
- More or less marked increase in intracranial pressure (ie the pressure that the brain exerts against the bones of the skull). Especially if severe, the increase in intracranial pressure can cause symptoms such as:
- Persistent headache;
- Poor eyesight;
- He retched;
- Irritability;
- Hearing problems;
- Respiratory problems;
- Changes in mental status;
- Papilledema.
- Deficits of intellectual development, which imply a reduced capacity of intellect ( low IQ ). The reduced ability of intellect varies enormously from patient to patient and depends on the severity of the malformation induced by the process of premature fusion of the cranial sutures;
- Facial anomalies, including:
- Flat or concave face (due to lack of growth of the central bones of the face);
- Puffy, protruding and wide-open eyes; shallow eye sockets and abnormally spaced eyes (hypertelorism of the eye sockets);
- Beak nose;
- Underdeveloped jaw combined with prognathism;
- Crowded teeth (due to the underdeveloped jaw);
- Ears at a lower height than the norm.
Syndactyly
In carriers of Apert syndrome, syndactyly is observed in the hands, almost always, and in the feet, less frequently than in the hands.
The typical features of syndactyly in the hands of an individual with Apert syndrome are 4:
- Presence of a short thumb with radial deviation (that is, anomalously oriented towards the radium, one of the two bones of the forearm);
- Complex syndactyly between the index finger, the middle finger and the ring finger. With complex syndactyly, doctors mean an abnormal fusion of the fingers that affects not only the soft tissues (the skin), but also the bone tissues (the phalanges);
- Sinfalangismo . It is the medical term that indicates the anomalous fusion of the interphalangeal joints of the fingers (the interphalangeal joints are the articular elements present between phalanx and phalanx);
- Simple syndactyly between the fourth and fifth finger (ie between the ring finger and the little finger). With simple syndactyly, experts refer to an abnormal fusion of the fingers that affects only the soft tissues (the skin).
SEVERITY OF SYNDACTYLOUS IN THE OPEN SYNDROME: THE 3 TYPES
Based on the severity of the malformation of the thumb (before the four characteristics), experts in the subject of Apert syndrome distinguish 3 types of syndactylia of increasing severity:
- Type I (the least serious) coincides with a minimal anomaly of the thumb, which remains totally independent of the index.
Other anomalies: index, middle and ring finger are fused together through a complex syndactyly and present sinfalangismo in charge of the distal interphalangeal joints; there is simple and incomplete syndactyly between ring finger and little finger (incomplete syndactyly means that the fusion between two fingers is partial).
Other information: it is the most common type.
- Type II (intermediate gravity) is characterized by a more pronounced radial deviation of the thumb, compared to the previous case, and by a principle of syndactyly between the same thumb and the index finger (there is an incomplete syndactyly between thumb and index finger).
Other anomalies: index, middle and ring are protagonists of a complex syndactyly, combined with distal sinfalangismo; between the ring finger and the little finger there is a simple and incomplete syndactyly.
Other information: it is the second most common type.
- Type III (the most severe) is characterized by the presence of a thumb joined together in the index, not only in the soft tissues but also in the bone tissues.
Other anomalies: all the fingers are fused together, so much so that it is almost impossible to recognize them; there is only one nail; if among the first 4 fingers syndactyly is complex, between the ring finger and the little finger it is (as for the other types) simple and incomplete.
Other information: it is the rarest type.
Other possible symptoms and signs of Apert syndrome
In some cases, in addition to being associated with craniostenosis and syndactyly, Apert syndrome is related to the presence of: polydactyly (ie the presence of an extra finger in the hands or feet), hearing loss, recurrent ear infections and paranasal sinuses, hyperhidrosis, oily skin, severe acne, absence of hair on the eyebrows, fusion of the cervical vertebrae, obstructive sleep apnea syndrome and / or cleft palate.
Complications
The complications of Apert syndrome are, above all, the serious consequences that craniosynostosis can have on brain development and intellectual capacity, and on the functional capacities of the hands subject to syndactyly.
When is it possible to notice the Apert syndrome?
In general, cranial and digital abnormalities due to Apert syndrome are evident at birth, therefore diagnosis and treatment planning are immediate.
Diagnosis
As a rule, the course of investigations that leads to the diagnosis of Apert syndrome starts from the physical examination and the anamnesis ; therefore, it continues with a series of radiological examinations at the head (X-ray at the head, CT at the head and / or magnetic resonance at the head) and hands and eventually feet; finally, it ends with a genetic test .
Physical examination and medical history
Physical examination and anamnesis consist essentially in a careful examination of the symptomatology exhibited by the patient.
In a context of Apert syndrome, it is in these moments of the diagnostic procedure that the doctor ascertains craniostenosis and syndactyly, and their precise characteristics.
Radiological examinations of the head and fingers of hands and feet
In a context of Apert syndrome:
- X-ray head tests are necessary for the doctor to confirm the presence of an early fusion of the coronal sutures (coronal craniostenosis or brachycephaly); furthermore, they allow him to estimate the severity of the cranial-brain abnormalities in place.
- On the other hand, radiological examinations on the fingers and toes are fundamental not so much for the confirmation of syndactyly (for this the visual examination is sufficient), but rather to know in detail the connotations of interdigital fusions (type of syndactyly present, level merger, etc.).
Genetic test
It is the DNA analysis aimed at detecting mutations of critical genes.
In a context of Apert syndrome, it is the confirmatory diagnostic test, as it brings to light the FGFR2 mutation characteristic of the genetic disease in question.
Therapy
Currently, there is no cure for the mutation responsible for Apert syndrome; however, those who are carriers of this rare genetic disease can still improve their condition, as they have several symptomatic treatments at their disposal, that is therapies aimed at alleviating the symptoms, postponing the inevitable complications and, finally, eluding those that are avoidable.
Did you know that ...
In order to be able to recover from a disease such as Apert's syndrome, the genetic mutation in the embryonic phase should be eliminated, so that the cranial vault and fingers and toes grow adequately.
Symptomatic therapy: what does it consist of?
At the base of every symptomatic therapy adopted in the presence of Apert syndrome there are:
- Surgical treatment of brachycephaly and its consequences at a more mature age, e
- Surgical treatment of syndactyly .
Therefore, depending on the symptomatology exhibited by the patient, the doctor in charge could add to the aforementioned treatments:
- A therapeutic plan, sometimes even fairly invasive, against obstructive apnea syndrome;
- A therapeutic plan against the recurrence of paranasal sinus infections;
- A surgical treatment plan, designed to prevent ear infections (when these are recurrent; if they are not recurrent but sporadic, an antibiotic therapy is sufficient);
- A surgical treatment plan to solve possible anomalies, such as cleft palate, fusion of the cervical vertebrae etc.
THE SURGICAL CARE OF BRACHICEPHALIA
For the carrier of Apert syndrome, surgical treatment of brachycephaly includes:
- A first intervention at a young age (within the year of life), aimed at separating the fusal coronal sutures earlier than expected . If this intervention is successful, the brain has the right space for growth and there is a reduced risk of intellectual problems.
- A second intervention between 4 and 12 years, aimed at giving a normal appearance to the face, which (as the reader will remember) is flat if not even concave.
The operation in question involves the incision of some bones of the face and their repositioning according to a structure that reflects at least in part the normality.
- A third eventual intervention in the years of childhood, with the aim of eliminating or at least reducing the ocular Belarusianism .
SURGICAL CARE OF SYNDRILE TREATMENT
The surgical treatment of syndactyly varies according to the characteristics of the interdigital fusion (therefore it depends on the type).
This means that the intervention valid for an individual with Apert syndrome may not be equally valid for another individual with the same genetic disease (it is only if the type of syndactyla is the same).
Once this basic aspect has been clarified, the goal of every type of existing surgical approach is the same and consists in freeing the fingers merged together, in order to guarantee a certain functionality to the hands.
In general, the treatment of syndactyla involves two stages:
- 1 step: "freeing" the first interdigital space (space between thumb and index) and the fourth interdigital space (space between ring finger and little finger);
- 2 step: "freeing" the second and third interdigital space (space between index and middle, and space between middle and ring).
Prognosis
Without adequate treatment of craniostenosis, Apert syndrome has certainly a negative prognosis, with the patient developing even severe intellectual problems; with the practice of an appropriate intervention, on the other hand, the genetic disease in question can enjoy a benign prognosis, certainly not a negative one, with the patient presenting a normal or almost normal IQ.
Did you know that ...
Every 10 children with Apert syndrome that grow in the family, 4 of them develop a normal IQ.
Prevention
Apert syndrome is an impossible condition to prevent .
