Cruson Syndrome

A special genetic disease - Cruson's syndrome - is called craniofacial dysostosis in another way.

This pathology consists in abnormal penetration of the sutures between the cranial and facial bones.

[1], [2], [3]

Epidemiology

Cruson syndrome is found in about 5% of the cases of cranial fusion of the bones, which took place from the birth of the child. So, the frequency of pathology can be estimated as 17 cases per 1 million births.

[4], [5], [6]

Causes of the cruson Syndrome

To date, quite a large number of various clinical and laboratory studies of the causes of this disease have already been conducted. Scientists came to the unequivocal conclusion that the syndrome has an autosomal dominant pathway of genetic inheritance.

This means that if there is a mutation gene in one parent chain (maternal or paternal), then there is a 50% risk of having a baby with the symptoms of Cruson syndrome.

Children inherit a damaged chromosome not always. Moreover, they may not even be carriers of a defect. Therefore, parents, one of which has a mutated gene in the family, has every chance of giving birth to a healthy child. The main thing - carefully monitored before the planning of pregnancy.

Thus, we can distinguish the following risk factors:

• presence of one of the parents or blood relatives of Cruson syndrome;
• carriage of a mutated gene by one of the parents;
• the age of the father is over 60 years (for the period of conception of the child).

[7], [8], [9], [10], [11]

Pathogenesis

The pathogenesis of the syndrome is simple: the disorder provokes a gene mutation of fibroblast growth factor FGFR2. This gene is located in a specific chromosome (10q26) and consists of 20 sites with gene information. The change that leads to the appearance of Cruson syndrome is most often found in the seventh and ninth gene.

In general, the FGFR2 gene may contain 35 mutational changes that affect the development of the syndrome. Most often, such a violation occurs on the paternal line.

All small children have seams - small gaps between the elements of the bones of the skull and face. As the baby grows and develops, his brain grows, and, thanks to these seams, the corresponding expansion of the skull occurs. Suture gaps fuse only when the brain is finally formed and ceases to grow.

In children with Cruson syndrome, the sutures are overgrown much earlier than necessary. Therefore, the growing brain is forced to "adapt" to the space that is available. Outwardly it becomes noticeable by the non-standard form of the cranium, face and dentition.

[12], [13]

Symptoms of the cruson Syndrome

The first signs of the syndrome are visible immediately after the birth of the child. They can be observed in the face and skull:

1. change the shape of the middle facial part;
2. changing the shape of the nose;
3. speaking tongue;
4. short and low lip;
5. insufficient jaw closure.

• The bone system is undergoing changes. The following types of deformation of the skull can appear:

1. Trigoncephaly - wedge-shaped head with an enlarged occipital and narrowed frontal part;
2. skaphoccephaly - scaphoid head shape with an elongated low set skull and narrow forehead;
3. brachycephaly - short-headedness, or too wide head with a shortened skull length;
4. defect Kleeblattschadel is a hydrocephaloid deformity of the skull in the form of a shamrock.

Palpatorally, one can feel flat seams on the skull. But this can be done not always, as the overgrowth of the joints can occur at any stage:

1. at the stage of embryonic development;
2. in the first year of life of the baby;
3. closer to the 3rd year;
4. up to 10 years of age.

• There are violations in the visual organs:

1. primary or secondary exophthalmos - protrusion of the eyes, in which the eyeball remains unchanged;
2. nystagmus - frequent involuntary fluctuations of eyeballs;
3. versatile strabismus - wrong divergent position of the eyes;
4. hypertelorism - an increased interval between the inner corners of the eyes and pupils;
5. ectopia - deviation of the pupil or lens from the center;
6. coloboma - lack of part of the iris;
7. megalocornea - pathological enlargement of the cornea.

• There are also defects in the auditory organs:

1. conductive deafness;
2. change the shape of the internal auditory canal;
3. lowering of sound conduction of bones;
4. atresia of the external auditory canal.

As can be seen from the clinical picture, all the symptoms of the disease are localized only in the head region. It is characteristic that in this case there are no violations of the vestibular apparatus.

[14], [15], [16]

Complications and consequences

Cruson's syndrome can not pass without a trace: as a rule, the child has various consequences and complications:

• hydrocephalus;
• deterioration of vision, up to loss (due to prolonged compression of the optic nerve, irreversible changes occur in it);
• thinning and ulcerative damage to the cornea (due to the excessive bulge of the eyeballs, it becomes impossible to completely close the eyelids, as a result of which the cornea partially dries up and becomes covered with ulcers);
• mental retardation;
• difficulties with adaptation in society (mental inferiority and unpleasant external manifestations of the syndrome greatly complicate the patient's interaction with the society).

Another complication of the syndrome may be the Arnold-Chiari anomaly - a movement of the cerebellar tonsils through the large occipital opening to the cervical vertebrae.

[17], [18]

Diagnostics of the cruson Syndrome

First of all, the doctor conducts an examination of a sick child. He can clarify whether this happened in the family, because the symptoms of Cruson syndrome are quite typical, and it's difficult to confuse them.

To clarify the diagnosis, the doctor will be helped by instrumental diagnostics, which is carried out without fail as soon as the syndrome is suspected.

Radiography will indicate the stage of infection of the lambdoid, coronary and sagittal sutures. In addition, this method helps detect a decrease in paranasal sinuses, signs of basilar kyphosis, an enlarged pituitary fossa, an irregular shape of the orbit.

Deformation of the internal auditory canal is observed topographically. Also, with the topogram of the temples, one can trace the external rotation of the rocky part of the pyramid, which takes place against the background of the dysplasia of the base of the skull. Visually, this is manifested by hyperostosis, oblique orientation of the auditory canals, an abnormal course of the facial nerve.

Computer tomography or MRI confirms these signs:

• atresia;
• narrowing of the external auditory canal;
• deformation of the chambers of the mastoid process and stapes;
• absence of a tympanic cavity;
• ankylosis malleus;
• violation of the development of the periosteal section of the labyrinth.

In addition, the doctor can refer the patient to a consultation with other specialists who will prescribe tests and other studies at their own discretion. For example, with the suspicion of Cruson syndrome, it is appropriate to consult a geneticist, a psychiatrist, a neurologist, an eye doctor, a neurosurgeon.

[19], [20], [21]

Differential diagnosis

Differential diagnosis is performed with isolated craniostenosis, Apert syndrome, Sethre-Chotzen syndrome and Pfeiffer.

Treatment of the cruson Syndrome

Unfortunately, Cruson's syndrome can not be fully cured. Therapeutic measures can be directed to a functional and cosmetic correction: this can only be achieved surgically. During the operation, the surgeon partially opens the synostosed sutures, and also corrects the position of the eyeball.

We describe in more detail the process of surgical treatment of Cruson's syndrome. Such treatment is better to be performed at 4-5 years of age. Thanks to surgery, the maxillary hypoplasia is corrected, the dentition is restored and the exophthalmos is removed (the lower edge of the eye sockets extends and increases in volume). During the intervention to establish the bite, the doctor fixes the jaws with special plates, which will be removed only after 1-1.5 months.

Modern medicine uses distraction methods for correcting deformations of the facial bones. There are special devices for the displacement of almost any part of the skull, both from the front and from the occipital side. Such treatment is only gaining momentum, and with time you can hope that the correction of bone defects will become more sparing and effective.

Drug therapy in the curative scheme with Cruson syndrome is not the main one. So, drugs can only be used to relieve the patient's condition.

Nootropic drugs
	Pyracetam	Pantogam
Dosing and Administration	Usually prescribed 30-50 mg Piracetam per day. The treatment is long.	The daily amount of the drug in Cruson syndrome can be from 0.75 to 3 g. Duration of therapy - up to 4 months (sometimes longer, at the discretion of the doctor).
Contraindications	Renal failure, diabetes, children under 1 year.	Acute violation of renal function, phenylketonuria, a tendency to allergies.
Side effects	Overexcitement, irritability, sleep and appetite disorder, headache.	Allergies, sleep disorders, tinnitus.
Special instructions	It is not recommended to take more than 5 grams of the drug per day.	If the treatment is long, Pantogam is not recommended to be combined with other nootropic drugs.

Vascular medications
	Cavinton	Cinnarizine
Dosing and Administration	In Crouzon's syndrome, a prolonged course of treatment with the intake of 5-10 g of the drug three times a day is practiced.	The drug is long, 75 mg per day.
Contraindications	Severe heart disease, heart rhythm disturbances, unstable blood pressure.	Allergic inclinations.
Side effects	Heart palpitations, lowering of blood pressure.	Sleep disorders, indigestion.
Special instructions	The drug can not be combined with heparin.	The drug enhances the effect of sedatives.

Diuretics
	Lasix	Diakarb
Dosing and Administration	The treatment regimen for Cruson syndrome is individual and depends on the indications.	Assign an average of 0.25 grams 1-4 times a day.
Contraindications	Renal dysfunction, hypokalemia, dehydration, difficulty with urination, a tendency to allergies.	Acidosis, diabetes mellitus.
Side effects	Weakness in the muscles, cramps, pain in the head, arrhythmia, hypotension.	Drowsiness, fatigue, headache, anemia.
Special instructions	During the treatment, constant medical supervision is necessary.	Do not use for a long time.

Prevention

Prevention of the birth of children with Cruson syndrome is not possible, due to the fact that this disease in the vast majority of cases is hereditary.

Since sometimes there are sporadic cases of the syndrome that may be associated with the elderly age of the child's father at the time of conception, it is recommended that we carefully weigh the risk level when planning such a "late" pregnancy.

If the genus has already been reported as having children with Cruson syndrome, then it makes sense for parents to undergo a complete examination with a geneticist, for the presence of a mutated FGFR2 gene.

For all pregnant women, regardless of the quality of their heredity, it is recommended that they become registered in the LC in time (no later than 12 weeks) and regularly visit a gynecologist.

[22], [23]

Forecast

Unfortunately, even after successful surgical intervention, no one can absolutely guarantee the positive dynamics of such a disease as Cruson's syndrome. Often, the patient is completely or partially impaired visual function due to atrophic changes in the optic nerve. Because of the irregular shape of the orbit, there are problems with retention of the eyeball. Over time, bone defects become more pronounced.

However, many patients still manage to be socially adapted for a long time, regardless of the degree of manifestation of the disease. It remains to be hoped that the level of medicine is progressing, and in the near future there will still be methods to prevent and treat any gene disorders, including Cruson's syndrome.