Genetics
There is still some discussion on whether FND is sporadic or genetic. The majority of FND cases are sporadic. Yet, some studies describe families with multiple members with FND. Gene mutations are likely to play an important role in the cause. Unfortunately, the genetic cause for most types of FND remains undetermined. Frontorhiny
The cause of frontorhiny is a mutation in the ALX3 gene. ALX3 is essential for normal facial development. Different mutations can occur in the ALX3 gene, but they all lead to the same effect: severe or complete loss of protein functionality. The ALX3 mutation never occurs in a person without frontorhiny. Acromelic frontonasal dysostosis
Acromelic frontonasal dysostosis is caused by a heterozygous mutation in the ZSWIM6 gene. It is thought that acromelic frontonasal dysostosis occurs due to an abnormality in the Sonic Hedgehog (SSH) signaling pathway. This pathway plays an important role in developing the midline central nervous system/craniofrontofacial region and the limbs. Hence, it is plausible that an error in the SSH pathway causes acromelic frontonasal dysostosis, because this syndrome not only shows abnormalities in the midfacial region, but also in the limbs and CNS. Diagnostics
The main diagnostic tools for evaluating FND are X-rays and CT-scans of the skull. These tools could display any possible intracranial pathology in FND. For example, CT can be used to reveal widening of nasal bones. Diagnostics are mainly used before reconstructive surgery, for proper planning and preparation.Prenatally, various features of FND (such as hypertelorism) can be recognized using ultrasound techniques.
Patient are characterized by: hypertelorism, a wide nasal bridge, a split nasal tip, a broad columella (strip of skin running from the tip of the nose to the upper lip), widely separated narrow nostrils, a long philtrum (vertical groove on the upper lip) and two-sided nasal swellings.Frontorhiny is one of the two subtypes of FND where a genetic mutation has been determined. The mutation has an autosomal recessive inheritance pattern. The syndrome is often seen in siblings and, most of the time, parents are carriers. See Genetics. Craniofrontonasal dysplasia
Craniofrontonasal dysplasia (CFND) is a rare type of FND with X linked inheritance. Multiple features are characteristic for CFND such as craniosynostosis of the coronal sutures (prematurely closed cranial sutures), dry frizzy curled hair, splitting of the nails and facial asymmetry.There is a large variety in phenotype. Women present with a more severe phenotype than men. Females characteristically have FND, craniosynostosis and additional small malformations. Males are usually more mildly affected, presenting with only hypertelorism. The gene that causes CFND is called EFNB1 and is located on the X chromosome. A hypothesis for the more severe outcome in females is based on X-inactivation, which leads to mosaicism. As a result, patients have less functional cells, generating abnormal tissue boundaries, termed "cellular interference". This process almost never occurs in males, as they have less mutagenic material in their genes. EFBN1 also has an important function in males. As the syndrome has an X-linked inheritance pattern, there is no man-to-man inheritance.