He Apert syndrome Or acrocephalosyndactyly type I (ACS1), is a pathology of genetic origin that is characterized by the presence of different alterations and malformations in the skull, face and extremities (Boston Children's Hospital, 2016).
At a clinical level, Apert syndrome is characterized by the presence or development of a pointed or elongated skull, a sunken facial area with a Alteration in the projection of the teeth, fusion and closure of the bones of the fingers and joints, variable mental retardation, alterations of Language, etc. (The National Craniofacial Association, 2016).
Although this pathology may be hereditary, in most cases Apert syndrome occurs without the presence of a family history, Due essentially to a de novo mutation during the gestation phase (Ruiz Cobo and Guerra Diaz, 2016).
The genetic mechanisms that cause Apert syndrome are not exactly known. Several genetic alterations have been identified that are Capable of producing this pathology, essentially related to mutations in the FGFR2 gene (National Institute of Health, 2015).
On the other hand, the diagnosis of Apert syndrome usually begins with clinical suspicion in the prenatal period after the identification of anomalies in Routine ultrasound scans and is confirmed through a genetic study (Ruíz Cobo and Guerra Díaz, 2016).
As for treatment, there is no curative intervention for Apert syndrome. However, throughout the history of this Pathology, various specific interventions have been designed, which usually include neurosurgery, craniofacial surgery, maxillofacial surgery, Pharmacological, physical therapy, psychological and neuropsychological intervention, among others (Ruíz Cobo and Guerra Díaz, 2016).
Characteristics of Apert syndrome
Apert syndrome is a genetic pathology characterized by the presence of different skeletal malformations at the cranial, facial and / or The extremities (Genetics Home Reference, 2016).
The essential alteration of the syndrome of Apert is constituted by a premature or early closure of the cranial fissures, which causes a growth Abnormal of the rest of structures of the face and skull. In addition to these, malformations may also appear in the upper extremities and Such as the fusion of the fingers and toes (Genetics Home Referece, 2016).
On the other hand, Cognitive abilities Of people with Apert syndrome may also be affected, with a variable severity ranging from mild to (Genetics Home Reference, 2016).
Although Baumgartner (1842) and Wheaton (1894) made the first mention of this medical condition, it was not until 1906 that the specialist French physician Eugene Apert, accurately describes this syndrome and publishes the first clinical report (Pi et al., 2003).
In his publication, Eugene Apert, describes a set of new cases of patients affected by a well-defined malformative pattern characterized by The signs and symptoms characteristic of this pathology (Arroyo Carrera et al., 1999).
Thus, it was not until 1995 when the genetic etiological factors of Apert syndrome were identified. Specifically, Wilkie et al. Described the presence of two mutations in the FGFR2 gene in about 40 affected patients (Arroyo Carrera et al., 1999).
In addition, Apert syndrome is a medical condition that is classified within the diseases or pathologies characterized by presenting Craniosynostosis (Premature closure of the cranial sutures).
Other pathologies belonging to this group are Pfeiffer's syndrome, Crouzon's syndrome, the syndrome Of Saethre-Chotzcen and Carpenter syndrome (Ruíz Cobo and Guerra Diaz, 2016).
About us
Apert syndrome is considered a rare or rare disease, ie, it has a prevalence of less than one case per 15,000 Inhabitants of the general population.
Specifically, Apert syndrome occurs in about one person for every 160,000-200,000 births, and there is a 50% likelihood of Transmit this pathology at the hereditary level (Children's Craniofacial Association, 2016).
Furthermore, in terms of sex distribution, a higher prevalence in men or women has not been identified, nor is it associated with ethnic or Particular geographic locations.
At present, and since Apert syndrome was identified in approximately 1984, in the clinical reports and in the medical literature that have published More than 300 cases of this pathology (National Organization for Rare Disorders, 2007).
Signs and symptoms
Clinical manifestations of Apert syndrome usually include malformation or incomplete development of the cranial structure, a phenotype or pattern Atypical facial and skeletal alterations in the extremities.
In the case of Apert syndrome, central involvement is related to the formation and closure of the skull's skeletal structure. During development Embryonic, there is a process called creneosinostosis, characterized by premature closure of the cranial sutures (Landete, Pérez-Ferrer and Chiner, 2013).
Fractures or cranial sutures are a type of bands of fibrous tissue that have the fundamental purpose of connecting the bones that make up the skull (Frontal, occipital, parietal and temporal) (National Institutes of Health, 2015).
During the gestation phase and the early postnatal period, the bony structure that makes up the skull is held together thanks to these fibrous tissues And elastic (National Institutes of Health, 2015).
Normally, the cranial bones do not usually fuse until approximately 12 or 18 months. The presence of spaces or soft spots between the bones Is part of normal child development (National Institutes of Health, 2015).
Therefore, throughout the infantile stage, these sutures or flexible regions, allow the brain to grow of accelerated form and, in addition, protects of it Impacts (National Institutes of Health, 2015).
Thus, in Apert syndrome, premature closure of these cranial sutures and cranial bones makes normal growth development impossible Cranial and cerebral (Children's Craniofacial Association, 2016).
Consequently, the most frequent signs and symptoms of Apert syndrome may include (Ruíz Cobo and Guerra Díaz, 2016):
Craniofacial abnormalities and abnormalities
- Craniosynostosis: The early closure of the skull sutures causes a wide variety of craniofacial alterations, Which may include inadequate expansion of brain structures, development of papillary edema (inflammation of the ocular blind spot where the Optic atrophy (injury or deficit affecting ocular function) and / or intracranial hypertension (abnormal increase in
cerebrospinal fluid). - Unilateral or bilateral facial hypoplasia : The head presents an atypical appearance with a deficient or incomplete development of some Of their halves. At the visual level, a sunken face is observed, with prominent eyes and drooping eyelids.
- Proptosis or exophthalmos: Significant and abnormal protrusion of the eyes towards the exterior of the ocular cavity.
- Macroglossia: Increased tongue size due to the presence of a higher than normal tissue volume.
- Mandibular malocclusion: The presence of different alterations related to the growth of the bone structure of The jaw that prevent proper functioning and close the masticatory system or apparatus.
- Cleft Palate: Presence of a hole / fissure in the central or middle area of the palate.
Musculoskeletal abnormalities and abnormalities
This type of alterations fundamentally affect the upper and lower extremities, usually to the fusion and development of the fingers.
- Syndactyly: Abnormal and pathological fusion of one or more fingers to each other, on the hands or feet. Various Variants, type I (fusion of 2nd, 2nd and 4th finger), type II (5th finger fusion), type III (fusion of all fingers).
Generally, the syndactyly type I is more common in the hands, whereas in the feet, type III syndactyly is more frequent.
In addition to these, it is also possible to observe other clinical findings at musculoskeletal level, shortening of various bones (radius, humerus, femur), Hypoplasia of scapula or pelvis, fusion of cervical vertebrae.
As a consequence, many sufferers will have reduced joint mobility and, therefore, may develop various Acquisition of gross and fine motor skills.
Skin and Dermatological Alterations and Anomalies
These types of anomalies are very heterogeneous and variable among the affected individuals; however, some of the most common ones have been identified:
- Hyperhidrosis: Excessive sweating, especially in the hands and feet.
- Mucosclerosis or crust lesions: The most frequent is the presence of cutaneous lesions of the acneiform type.
- Hypopigmentation: Changes in skin color that involve a decrease in pigmentation.
- Skin thickening: Abnormal increase of skin thickness in one or more areas.
Visceral abnormalities and abnormalities
The aetiological alteration of this pathology, can give rise to the development of lesions or secondary pathologies at morphological and structural level in Various body areas, some of them include:
- Malformation in the central nervous system: Has been observed in some cases the development of Agenesis or hypoplasia of the corpus callosum (Absence or partial development) and various structures of the Libyan system. In addition, abnormal or altered development of Cerebral white matter.
- Genito-urinary malformations: In the case of male patients, posterior urethral valves may Kidney failure and Hydronephrosis . On the other hand, in the case of the women affected, the presence of malformations in the clitoris is frequent.
- Cardiac malformations: Alterations related to cardiac function and the heart are usually associated with the presence of Left ventricular hypoplasia or ventricular septal defect.
Cognitive / psychological alterations and abnormalities
Although, in many cases it is possible to observe the presence of a general alteration of the cognitive functions and of the intellectual level, the delay Mental disorder is not present unequivocally in all cases of Apert syndrome.
In addition, in cases where there is an affectation of the intellectual level, it can be variable, on a scale of mild to moderate.
On the other hand, in the linguistic area, it is frequent the development of several deficits, related mainly to the articulation of the sounds Product of mandibular and buccal malformations.
Causes
Apert syndrome is due to the presence of a specific mutation in the FGFR2 gene. Experimental studies have indicated that, this gene is responsible Of the production of a protein, termed growth factor receptor 2 Fibroblasts (Genetics Home Reference, 2016).
Among the functions of this factor, we describe the sending of different chemical signals to immature cells to cause their transformation and Differentiation in bone cells during the fetal or prenatal development phase (Genetics Home Reference, 2016).
Therefore, the presence of mutations in the FGFR2 gene alters the performance of this protein and, therefore, may cause early fusion of Bones of the skull, hand and feet (Genetics Home Reference, 2016).
Diagnosis
Much of the clinical features of Apert syndrome can be identified during gestation, specifically in ultrasound Pregnancy and fetal development.
In this way, when there is a clinical suspicion, a genetic study is recommenced to identify the presence of a mutation Genetics compatible with Apert syndrome.
On the other hand, when signs are subtle or have not been identified before birth, after this it is possible to perform a detailed physical analysis And various genetic tests to confirm the diagnosis.
Is there treatment for Apert syndrome?
Although there is no specific cure for Apert syndrome, several approaches have been described for the treatment of symptoms and Medical complications of this pathology.
The most effective therapeutic interventions are those that are implemented early, in the first moments of life and involve professionals From different areas (Children's Craniofacial Association, 2016).
Typically, treatment of affected children requires individualized planning, with scheduling of multiple surgeries (Children's Craniofacial Association, 2016).
Thus, the management of this pathology is based on the correction of skeletal and craniofacial malformations, and the psychological and neuropsychological support (Ruíz Cobo and Guerra Díaz, 2016).
Through the neurosurgery the reconstruction of the cranial vault is sought, whereas the specialists in the maxillofacial surgery try to correct the Facial malformations (Ruiz Cobo and Guerra Díaz, 2016).
On the other hand, it is also frequent the participation of surgeons of trauma, for the reconstruction of the malformations present in the hands and feet.
In addition, the design of individualized programs of early stimulation, rehabilitation of communication, Social skills training or the Psychoeducational monitoring, are beneficial for the achievement of an optimal, functional and independent development of the affected individuals (Ruíz Cobo and Guerra Díaz, 2016).
References
- Arroyo Carrera, I., Martínez-Frías, M., Marco Pérez, J., Paisán Grisolía, L., Cárdenas Rodríguez, A., Nieto Conde, C.,. . . Lara Palma, A. (1999). Syndrom De Apert: clinical-epidemiological analysis of a consecutive series of cases. Fetal Medicine and Neonatology.
- Boston Children's Hospital. (2016). Apert syndrome. Retrieved from Boston Children's Hospital.
- Children's Creniofacial Association. (2016). A Guide to Understanding Apert Syndrome. Children's Creniofacial Association. Obtained from Children's Craniofacial Association.
- Genetics Home Reference. (2016). Apert syndrome. Retrieved from the Genetics Home Reference.
- Landete, P., Pérez-Ferrer, P., & Chiner, E. (2013). Apert syndrome and sleep apnea. Arch Bronconeumol, 364-368.
- NIH. (2015). Apert Syndrome. Obtained from MedlinePlus.
- NIH. (2015). Cranial Sutures. Obtained from MedlinePlus.
- NORD. (2007). Apert Syndrome. Retrieved from the National Organization for Rare Disorders.
- Pi, G., Zúñiga, A., Cervera, J., & Ortiz, M. (2014). Prenatal diagnosis of Apert syndrome by mutation of nine in FGFR2 gene. An Peditr, 104-105.
- Ruiz Cobo, R., & Guerra Díez, L. (2016). Chapter X. Apert Syndrome. Obtained from Feaps.