Apera Syndrome

Syndrome Apera (Aperta) is a genetic pathology, as a result of which there are defects in the development of the skull (wide-set eyes, an unnecessarily high skull), and in addition to the lower and upper extremities (fingers on them fully fused, and additional ones may also appear).

[1], [2]

Epidemiology

Epidemiological indicators: similar cases occur 1 per 160 thousand Patients with this pathology account for approximately 4.5% of all cases of craniosynostosis.

[3], [4],

Causes of the aper's syndrome

The development of the syndrome is provoked by a violation in the structure of the gene located in the 10th chromosome. This gene is responsible for the process of separation of fingers, and in addition for timely closure of cranial sutures.

In addition, the causes of the appearance of pathology are the infectious diseases transferred during the period of gestation (such as rubella or tuberculosis, syphilis or influenza, as well as meningitis), mother radiation with X-rays. Most often, a similar syndrome is found in children born to elderly parents.

[5], [6], [7]

Pathogenesis

Syndrome Apera is transmitted by hereditary path. His type is autosomal dominant (ie, in a family in which one of the parents is sick, the probability of a baby with this disease is 50-100%).

The unique growth factor of fibroblast receptor 2 (FGFR2) due to mutation leads to an increase in the number of progenitor cells that develop along the osteogenic pathway. Ultimately, this leads to increased formation of the subperiosteal bone matrix and premature ossification of the cranial sutures during fetal development. The order and speed of suture melting determine the degree of deformation and disability. After the suture material grows, the growth of other tissues perpendicular to this suture becomes limited, and the merged bones act as a single bone skeleton.

The first genetic evidence that syndactyly in Aper's syndrome is a consequence of a defect in the keratinocyte receptor growth factor (KGFR) has been the observation of a correlation between the expression of KGFR in fibroblasts and the severity of syndactyly.

Amblyopia and strabismus is more common in patients with the mutation FGFR2 Ser252Trp and atrophy of the optic nerve disk is more common in patients with the FGFR2 Pro253Arg mutation. In patients with FGR2 Ser252Trp, mutations have a significantly higher prevalence of visual impairment compared to patients with FGFR2 Pro253Arg mutation.

[8], [9], [10],

Symptoms of the aper's syndrome

Individual manifestations of the disease are clearly visible even at the birth of the baby, because they develop even inside the mother's womb. Among the main symptoms of the syndrome:

• The skull is deformed - stretched to the height, becoming a kind of "tower"; In addition, the eyes are widely planted and slightly protruding (because the size of the eye orbits decreases); the nose widens and an incorrect bite is formed (upper teeth protrude excessively);
• The toes of the limbs are fully fused (mostly unmarked, and also middle with the index) and look like a skin membrane or full fusion of bones; In addition, extra fingers may grow;
• Delay in mental development (not at all);
• The optic nerves are atrophied, resulting in visual acuity decreasing (in some cases, a complete lack of vision develops);
• Increased intracranial pressure, resulting from too early overgrowth of cranial sutures - manifests as headaches and vomiting with nausea;
• Since the upper jaw has remained underdeveloped, there are problems with breathing;
• Sleep apnea syndrome is common.
• Emotional manifestations - aggression, lack of restraint, strong temper.

[11], [12], [13], [14]

Complications and consequences

Most patients have some degree of obstruction of the upper respiratory tract in infancy. The upper respiratory tract due to the decrease in the size of the nasopharynx and the khoans have poor permeability, the lower respiratory tract due to the anomalies of the cartilage trachea can lead to early death.

[15], [16]

Diagnostics of the aper's syndrome

The following measures are required for the diagnosis:

• The doctor should analyze the patient's complaints, as well as the medical history. It is necessary to find out whether there were any cases of development of such a pathology in the family;
• Neurological examination to assess the shape of the skull and the intellectual development of the patient (special questionnaires, as well as conversation);
• Examination of the fundus to identify the presence of symptoms of increased intracranial pressure (edema DZN, as well as blurriness of its edges);
• To assess the condition of the skull, its radiography is performed;
• Computer, as well as magnetic resonance imaging of the head to layer-by-layer the structure of the brain with the skull, to determine the presence of symptoms of premature fusion of the cranial sutures, and in addition to hydrocephalus (due to increased intracranial pressure, a surplus of CSF accumulates (this cerebrospinal fluid that facilitates the exchange process substances, as well as nutrition of the brain));
• X-ray of the feet with brushes to find out the cause, because of which there was a fusion of fingers (this is important for planning subsequent surgical intervention);
• A consultation with a medical geneticist and a neurosurgeon may be prescribed.

[17], [18]

Analyzes

Genetic analysis of frequent mutations occurring in the gene of type FGFR2 is carried out.

[19], [20], [21], [22]

Differential diagnosis

Differentiate this syndrome with other genetic pathologies, in which craniosynostosis is observed. These are diseases such as Pfeiffer, Cruson, and Sethra-Chotzen and Carpenter syndromes. To exclude these anomalies, molecular-genetic methods of testing are used.

Treatment of the aper's syndrome

Performing a surgical operation is considered to be the only effective method of treating the Apera syndrome - it helps to correct individual physical defects, and also corrects the backwardness in mental development.

In the process of this procedure, closing the coronal suture is performed in order to prevent possible trauma to the brain. The most common method is craniofacial distraction, in which the gradation of the skull is performed. To remove individual defects on the face, an orthodontic and / or orthognathic operation is performed.

In addition, patients surgically remove the fusion of the fingers.

Prevention

Since the Apera syndrome is a hereditary pathology, there is no way to prevent its occurrence.

[23], [24], [25], [26], [27],

Forecast

Syndrome Apera has an unfavorable prognosis for the further development and life of the child. Exception is made only by children who reached maturity without any cardiac pathologies.

[28], [29], [30], [31], [32]