The syndrome of Apert 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 limbs (Boston Children’s Hospital, 2016).
At a clinical level, Apert syndrome is characterized by the presence or development of a pointed or elongated skull, sunken facial area with an alteration in the projection of the teeth, fusion and closure of the bones of fingers and joints, mental retardation variable, language alterations , etc. (The National Craniofacial Association, 2016).
Although this pathology can be hereditary, in most cases, Apert syndrome occurs without the presence of a family history, essentially due to a de novo mutation during the gestation phase (Ruíz Cobo and Guerra Díaz, 2016).
The genetic mechanisms that cause Apert syndrome are not known exactly. Currently, 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 abnormalities in routine ultrasound ultrasounds and is confirmed through the performance of a genetic study (Ruíz Cobo and Guerra Díaz, 2016).
Regarding treatment, there is no type of curative intervention for Apert syndrome. However, throughout the history of this pathology, various specific interventions have been designed that often include neurosurgery, cranio-facial surgery, maxillofacial surgery, pharmacological treatment , 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 limb levels (Genetics Home Referece, 2016).
The essential alteration of the Apert syndrome is constituted by a premature or early closure of the cranial fissures, which causes an abnormal growth of the rest of the structures of the face and the skull. In addition to these, malformations may also appear in the upper and lower extremities , such as the fusion of the fingers and toes (Genetics Home Referece, 2016).
On the other hand, the cognitive abilities of people suffering from Apert syndrome may also be affected, with a variable severity of mild to moderate (Genetics Home Referece, 2016).
Although Baumgartner (1842) and Wheaton (1894) make the first mention of this medical condition, it is not until 1906, when the French medical specialist Eugene Apert, accurately describes this syndrome and publishes the first clinical report (Pi et al. al., 2003).
In his publication, Eugene Apert, describes a set of new cases of patients affected by a well-defined malformation pattern and characterized by the signs and symptoms characteristic of this pathology (Arroyo Carrera et al., 1999).
Thus, it was not until 1995 when the etiological genetic factors of Apert syndrome were identified. Specifically, Wilkie and colleagues 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 into diseases or pathologies characterized by craniosynostosis (premature closure of cranial sutures).
Other pathologies belonging to this group are Pfeiffer syndrome, Crouzon syndrome , Saethre-Chotzcen syndrome and Carpenter syndrome (Ruiz Cobo and Guerra Díaz, 2016).
Apert syndrome is considered a rare or rare pathology, that is, it has a prevalence of less than one case per 15,000 inhabitants of the general population.
Specifically, the Apert syndrome occurs around one person for every 160,000-200,000 births and, in addition, there is a 50% probability of transmitting this condition at the hereditary level (Children’s Craniofacial Association, 2016).
Furthermore, in terms of gender distribution, a higher prevalence has not been identified in men or women, nor has it been associated with ethnic groups or particular geographical locations.
Currently, and given that the Apert syndrome was identified in 1984 approximately, in clinical reports and in the medical literature, they have published more than 300 cases of this pathology (National Organization for Rare Disorders, 2007).
Signs and symptoms
The clinical manifestations of the Apert syndrome usually include a malformation or incomplete development of the cranial structure, an atypical phenotype or facial pattern and skeletal alterations in the extremities.
In the case of Apert syndrome, the central involvement is related to the formation and closure of the bone structure of the skull. During embryonic development , a process called creneosinostosis takes place, characterized by a premature closure of cranial sutures (Landete, Pérez-Ferrer and Chiner, 2013).
Fissures or cranial sutures are a type of bands of fibrous tissue that have the fundamental objective 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 bone structure that makes up the skull stays together thanks to these fibrous and elastic tissues (National Institutes of Health, 2015).
Normally, the cranial bones do not usually fuse until about 12 or 18 months. The presence of spaces or soft spots between the cranial bones is part of normal childhood development (National Institutes of Health, 2015).
Therefore, throughout the infant stage, these sutures or flexible regions allow the brain to grow at an accelerated rate and, in addition, protect it from impacts (National Institutes of Health, 2015).
Thus, in the Apert syndrome, the premature closure of these cranial sutures and cranial bones precludes the normal development of cranial and cerebral growth (Children’s Craniofacial Association, 2016).
Consequently, the most frequent signs and symptoms of Apert syndrome may include (Ruíz Cobo and Guerra Díaz, 2016):
Alterations and craniofacial anomalies
- Craniosynostosis: the early closure of the sutures of the skull causes a wide variety of craniofacial alterations, among which may include inadequate expansion of the brain structures, development of papillary edema (inflammation of the ocular blind spot where the optic nerve arises ), optic atrophy (injury or deficit that affects ocular functionality) and / or intracranial hypertension (abnormal increase in cerebrospinal fluid pressure ).
- Unilateral or bilateral facial hypoplasia : the head presents an atypical appearance with a deficient or incomplete development of some of its halves. On a visual level, a sunken face is observed, with protruding eyes and drooping eyelids.
- Proptosis or exophthalmos: significant and abnormal protrusion of the eyes towards the outside of the ocular cavity.
- Macroglossia: increased tongue size due to the presence of a volume of tissue above normal.
- Mandibular malocclusion: the presence of different alterations related to the growth of the bony structure of the jaw are frequent, which prevent the correct functioning and closes the masticatory system or apparatus.
- Palatal cleft : presence of a hole / fissure in the central or middle part of the palate.
Alterations and musculoskeletal anomalies
This type of alterations affect mainly the upper and lower extremities, usually to the fusion and development of the fingers.
- Syndactyly: abnormal and pathological fusion of one or several fingers to each other, in the hands or feet. Several variants can be distinguished , type I (fusion of the 2nd, 2nd and 4th finger), type II (5th finger fusion), type III (fusion of all the fingers).
Generally, type I syndactylia is more common in the hands, while type III syndactyly is more common in the feet.
In addition to these, it is also possible to observe other clinical findings at the musculoskeletal level, shortening of various bones (radius, humerus, femur), hypoplasia of the scapula or pelvis, fusion of cervical vertebrae.
As a result, many affected will have reduced joint mobility and, therefore, may develop various difficulties for the acquisition of gross and fine motor skills.
Alterations and cutaneous / dermatological abnormalities
This type of anomalies are very heterogeneous and variable among the affected individuals, however, some of the most common have been identified:
- Hyperhidrosis: excessive increase in sweating, especially in the hands and feet.
- Maculo-vesiculous or crusted lesions: the most frequent is the presence of acneiform skin lesions.
- Hypopigmentation: changes in skin color that imply a decrease in pigmentation.
- Cutaneous thickening: abnormal increase of the thickness of the skin in one or several areas.
Alterations and visceral anomalies
The etiological alteration of this pathology can lead to the development of secondary lesions or pathologies at the morphological and structural level in various body areas, some of them include:
- Malformation in the central nervous system: it 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 libido system. In addition, an abnormal or altered development of cerebral white matter has also been described .
- Genito-urinary malformations: in the case of affected males, posterior urethral valves may appear that cause renal failure and hydronephrosis. On the other hand, in the case of affected women, 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 intraventricular communication.
Alterations and cognitive / psychological anomalies
Despite the fact that, in many cases, it is possible to observe the presence of a general alteration of cognitive functions and intellectual level, mental retardation is not present unequivocally in all cases of Apert syndrome.
In addition, in cases where there is an impairment of the intellectual level, it can be variable, on a scale of mild to moderate.
On the other hand, in the linguistic area, the development of diverse deficits is frequent, mainly related to the articulation of the sounds product of the mandibular and buccal malformations.
Apert syndrome is due to the presence of a specific mutation in the FGFR2 gene. Experimental studies have indicated that this gene is responsible for the production of a protein, called fibroblast growth factor receptor 2 (Genetics Home Reference, 2016).
Among the functions of this factor, it is described 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 functioning of this protein and, therefore, can cause early fusion of the bones of the skull, hand and feet (Genetics Home Reference, 2016).
Many of the clinical features of Apert syndrome can be identified during pregnancy, specifically in the ultrasound of pregnancy control and fetal development.
In this way, when there is a clinical suspicion, a genetic study is recommenced to identify the presence of a genetic mutation compatible with the Apert syndrome.
On the other hand, when the 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 condition.
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).
Normally, the treatment of affected children requires individualized planning, with the programming 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 psychological and neuropsychological support (Ruíz Cobo and Guerra Díaz, 2016).
Neurosurgery seeks to reconstruct the cranial vault, while specialists in maxillofacial surgery try to correct facial malformations (Ruíz Cobo and Guerra Díaz, 2016).
On the other hand, it is also frequent the participation of trauma surgeons, for the reconstruction of the malformations present in the hands and feet.
In addition, the design of individualized programs of early stimulation, communication rehabilitation, social skills training or psychopedagogical monitoring, are beneficial for the achievement of an optimal, functional and independent development of affected individuals (Ruíz Cobo and Guerra Díaz, 2016 ).