He Pfeiffer's syndrome Is a very rare genetic disorder that is c It is characterized by the early fusion of the bones of the skull, with deformations in the head and face. This abnormality is defined as craniosynostosis, which gives the appearance of bulging eyes. In addition, the affected people show alterations in the hands, as deviations in the fingers, and in the feet.
It takes its name from Rudolf Arthur Pfeiffer, a German geneticist who in 1964 described 8 patients of the same family who had abnormalities in the hands, feet and head.
It is part of a group of diseases that are a consequence of mutations in the FGFR genes. For example, him Apert syndrome , Crouzon syndrome , Beare-Stevenson syndrome, Jackson-Weiss syndrome.
Types of Pfeiffer's Syndrome
A classification that has been widely recognized for Pfeiffer's syndrome was published in 1993 by Michael Cohen. He proposed that three types could be given depending on their severity, so that types II and III are the most serious.
However, the three types have in common the presentation of enlarged thumbs and toes, Brachydactyly (Fingers shorter than normal) and Syndactyly (Malformation characterized by the congenital union of some fingers with each other).
- Type I : Or classical Pfeiffer syndrome, which is inherited by an autosomal dominant pattern and includes defects in the middle face. They usually have normal intelligence and can lead their lives without serious difficulties.
- Type II : This type does not appear to be hereditary, but appears sporadically, resulting in severe neurological difficulties and early death. It is detected by the shape of the skull, called"skull in cloverleaf"by the resemblance of the shape of the head to a three-leaf clover. This is due to an advanced fusion of the bones. Protrusions of the eyeballs (proptosis) are also frequently observed.
- Type III : It is not hereditary, and includes symptoms and manifestations similar to those of type II, but they do not present the deformity of the skull in the form of clover. Rather, it is characterized by having the shorter anterior cranial base. They share with the anterior type the ocular proptosis, by the little space that leaves the skull for the eyeballs. Sometimes the so-called natal teeth appear (already present some teeth at birth), and malformations in organs of the abdominal area or visceral abnormalities. On the other hand, they can show Mental retardation And severe neurological problems that can lead to early death.
More recently, specifically in 2013, Greig and colleagues developed a new system of classification of Pfeiffer's syndrome also in terms of severity. They studied 42 patients, basing their classification according to the evaluation of the neurological state, the airways, eyes and ears.
In addition, these assessments were performed before and after surgical procedures to observe how they evolved. The results indicated 3 types:
- Type A or minor problems : No change after operations.
- Type B or moderate problems : Postoperative functional improvement.
- Type C or serious problems : Significant improvement after the operation.
This latter classification is useful since it encourages multidisciplinary treatment.
What is its frequency?
Pfeiffer's syndrome affects both sexes equally and approximately occurs in 1 in 100,000 births.
What are its causes?
Pfeiffer's syndrome has an autosomal dominant pattern of inheritance. This means that only one copy of the affected gene is needed to trigger the disease, which can be provided by either parent. The risk of transmitting the anomalous gene from one parent to the child is 50% in each pregnancy.
However, it may also result from a new mutation (as we saw in types I and II).
Typology I is associated with mutations in both FGFR1 and FGFR2, whereas in types II and III they are linked to defects in the FGFR2 gene.
It is closely related to mutations in the growth factor receptor-1 gene of Fibroblasts (Or FGFR1) found on chromosome 8, or on gene 2 (FGFR2) on chromosome 10. The task of these genes is to encode the fibroblast growth factor receptors, which are essential for bone development properly.
It is also believed that a facilitator for the onset of this disease is for the father to be of advanced age when conceiving, since Mutations in sperm increase.
What are your symptoms?
The genetic and allelic heterogeneity of this syndrome seems to explain the phenotypic variability presented (Cerrato et al., 2014)
- Mainly, the characteristic facial and cranial features: abnormal growth of the head, fusion of the bones of the skull ( Craniosynostosis ), Frontal prominence, bulging eyes (proptosis) and hypertelorism (more orbits than normal). It is also habitual the head in pointed form or turribraquicefalia and the an underdevelopment in the medial third of the face.
- Type II shows the leaf clover-shaped head that we have already indicated, which is often linked to hydrocephalus (dilation of the ventricles by an accumulation of cerebrospinal fluid).
- Maxillary hypoplasia, or mandible poorly developed while showing a prominent lower jaw.
- Dental problems.
- Displaced ears.
- Hearing loss in 50% of those affected.
- Abnormalities in the upper extremities, specifically malformations in the thumbs and toes. They are large, widened and / or bent. Clinodactyly or angulation of one of the fingers.
- As already mentioned, fingers and toes exaggeratedly short (brachydactyly) or joining of the fingers (syndactyly or synphalangism).
- All patients with abnormalities in the upper limbs also had other milder limb anomalies according to Cerrato et al. (2014)
- Lack of mobility (ankylosis) and abnormal fixation of the elbow joints.
- Malformation of organs of the abdomen in severe cases.
- Respiratory problems.
- If it is type II or III, neurological problems and mental development can be caused by possible brain damage, or, Hypoxia (Due to respiratory difficulties that some of the affected also present). In contrast, Type I usually have intelligence within normal ranges.
- More serious cases: loss of vision secondary to an increase in intracranial pressure.
Possible complications
Obviously, the most serious cases are those that are going to evolve worse (types II and III). Since these are at risk of suffering neurological alterations and respiratory complications that can lead to an early death. In contrast, subjects with Pfeiffer syndrome type I improved markedly after treatment.
Associated disorders
- Apert Syndrome
- Crouzon Syndrome
- Jackson-Weiss Syndrome
- Beare-Stevenson Syndrome
- The Muenke syndrome
How is it diagnosed?
The diagnosis of Pfeiffer Syndrome can be made at birth, observing the premature attachment of the craniofacial bones, and the length and width of the thumbs and toes.
It should be noted that successful prenatal diagnosis becomes complicated, since the features of this syndrome can be confused with those of other disorders mentioned above (Children's craniofacial association, 2010).
How can it be treated?
It is very important that the treatment is performed early so that children with this syndrome do not see reduced their potential.
The treatment will focus on the symptoms that affect each individual in particular. That is, these should be individualized and guided according to the type and severity of the clinical presentation.
Usually requires a multidisciplinary and comprehensive approach, with a coordinated effort of a group of specialists. Among them would be necessary to include pediatricians, surgeons, otolaryngologists (doctors who treat ear, nose and throat problems), neurologists, audiologists (for hearing problems), among others.
Surgical treatment is advised to correct craniosynostosis, as it may cause other problems such as Hydrocephalus . In the case of the latter, an intervention may need to be performed by inserting a tube into the skull to drain the cerebrospinal fluid Excess of the brain. It can also be housed in other parts of the body, being suitable to be removed.
Surgery can also be used as a correct and reconstructive method in infants to help mitigate the effects of cranial malformations such as facial medial hypoplasia, nasal abnormalities, or ocular proptosis.
The results of this type of intervention can be variable. In a study by Clark et al. (2016) highlights the success of reconstructive plastic surgery in the treatment of proptosis and the ophthalmological complications typical of those affected by this syndrome.
In summary, specialists advise that during the first year of life can help an early surgical procedure to divide the cranial sutures that have closed and thus allow the skull and brain to grow normally.
The same can be done with the eye sockets, in order to maintain a good vision.
It is appropriate at a later age to correct half of the face with surgery to improve its physical appearance and position of the upper and lower jaw (Children's craniofacial association, 2010).
In some cases, you may opt for surgery to help correct ear malformations. In other cases, specialized hearing aids may be used to improve hearing.
Surgery also seems to be practiced in subjects with syndactyly or other skeletal malformations in order to achieve better functioning and increase mobility.
It is necessary to point out that the surgical procedures to correct the abnormalities associated with the disease will depend on the severity, state and location of the anomalies and the symptoms that they trigger.
In other cases where dental problems occur, it is appropriate to go to an orthodontic clinic. In any case it is recommended to go to a dentist at 2 years of age.
Another option to improve the mobility of the affected is to go to physiotherapy or opt for orthopedic measures.
A genetic consultation is recommended for the families of those affected. It is especially useful if the syndrome is suspected and in the family there are previous cases of this syndrome. An adequate clinical evaluation would detect in these cases of definitive form any sign or symptom, together with the physical features that can be associated with this condition.
However, we note that, as science advances, new and better ways of intervening in this disease are being developed.
A great support for affected people and families is to go to similar case associations and seek information. One such association is the Children's Craniofacial Association: www.ccakids.org, which has programs that are useful to address the special needs of these individuals and their families.
References
- Cerrato, F., Nuzzi, L., Theman, T., Taghinia, A., Upton, J., & Labow, B. (2014). Upper Extremity Anomalies in Pfeiffer Syndrome and Mutational Correlations. Plastic And Reconstructive Surgery, 133 (5), 654E-661E.
- Clark, J.D., Compton, C.J., Tahiri, Y., Nunery, W.R., & Harold Lee, H.B. (2016). Case report: Ophthalmic considerations in patients with Pfeiffer syndrome. American Journal Of Ophthalmology Case Reports, 21 -3.
- Cohen, M, M, (1993). Pfeiffer syndrome update, clinical subtypes, and guidelines for differential diagnosis. Am J Med Genet , Four. Five (3): 300-7
- Greig, A., Wagner, J., Warren, S., Grayson, B. & McCarthy, J. (2013). Pfeiffer Syndrome: Analysis of a Clinical Series and Development of a Classification System. Journal of Craniofacial Surgery: 24: 204-215.
- Redett, J. (2010). Guide to Understanding Pfeiffer's Syndrome . Retrieved from the Children's Craniofacial Association.
- Robin, H. N. (s.f.). Pfeiffer Syndrome . Retrieved June 14, 2016, from NORD National Organization for Rare Disorders.
- Pfeiffer syndrome . (S.f.). Retrieved on June 14, 2016, from Wikipedia.