InterGenetics is actively engaged since 2010 in the genetic evaluation of craniosynostosis and since 2005 for achondroplasia, both prenatally and postnatally, having reasonably gained a considerable experience in multifaceted management of these disorders.
Referrals are from general hospitals and maternity hospitals of Athens, from other regions of the country also from private maternity hospitals and private patients.
Cranio-skeletal malformations comprise a heterogeneous group of malformations affecting the size, shape and ossification of the skeleton and the skull.
Depending on the dominant clinical characteristic of these malformations, they can be divided into two major categories: skeletal malformations, mainly affecting the skeleton, and craniosynostosis, affecting the shape of the skull.
Collectively, skeletal dysplasias occur with a frequency of ~1/4000 births, while 25% of affected embryos die in utero and 30% in early infancy. An important genetic factor that is directly associated with cranio-skeletal malformations are the fibroblasts growth factor receptors (FGFRs).
Specifically, three typical skeletal malformations, i.e. achondroplasia, hypochondroplasia and thanatophoric dysplasia type 1 and 2are associated with mutations in the FGFR3 gene.
Genetic testing is important for disease classification and also for disease prognosis and management
Craniosynostosis refers to a distinct group of cranio-skeletal malformations of varying etiology, in which only 21% of cases are due to recognizable genetic causes. Of these, approximately 85% is due to predominantly to mutations in fibroblast growth factor receptor genes (FGFRs 1-3), while the remaining 15% is due to chromosomal abnormalities.
Craniosynostosis syndromes are a group of diseases, where one or more of the fibrous sutures of the skull are joined prematurely and ossified, influencing the development of the skull. As the skull is not able to grow properly, it compensates by growing more in the direction parallel to the closed sutures.
Sometimes, the resulting cranial development allows for the necessary space for the growth of the brain, but results in an abnormal head shape and abnormal facial features. In cases where the skull, due to the associated defect, cannot provide the required space for the developing brain, the results lead to increased intracranial pressure, which in turn may lead to visual impairment and/or mental retardation.
Finally, craniosynostosis may be part of a syndrome in 15 to 40% of patients, but is usually present as a single clinical finding.
By uncovering the genetic cause we can provide the necessary help regarding the reproductive options of the family
This group of genetic diseases occurs with a total frequency of 1 in 2000 births. Typically, treatment is achieved by timely and appropriate surgical interventions. Advanced paternal age has been clinically associated with de novo mutations for Crouzon syndrome, Apert syndrome, Pfeiffer syndrome, Beare-Stevenson syndrome and Muenke syndrome.
In general, prenatal diagnosis for most craniosynostosis syndromes is not widespread and is a sensitive issue, because, as already mentioned, these syndromes may on several occasions be treated through appropriate corrective surgery.
