[1] For the diagnosis of FND, a patient should present at least two of the following characteristics: hypertelorism (an increased distance between the eyes), a wide nasal root, vertical midline cleft of the nose and/or upper lip, cleft of the wings of the nose, malformed nasal tip, encephalocele (an opening of the skull with protrusion of the brain) or V-shaped hair pattern on the forehead.

FND seems to be sporadic (random) and multiple environmental factors are suggested as possible causes for the syndrome.

This table originates from the article ‘Acromelic frontonasal dysplasia: further delineation of a subtype with brain malformations and polydactyly (Toriello syndrome)', Verloes et al.

The other with hypotelorism (a decreased distance between the eyes), this includes holoprosencephaly (failure of development of the forebrain).

This causes the so-called widow's peak (a V-shaped hairline) in FND patients.

The developmental processes of the face and jaw structures originate from different primordia: [11] The formation of the frontonasal process is the result of a complex signaling system which begins with the synthesis of retinoic acid (a vitamin A metabolite).

This zone makes signaling molecules that stimulate the cell proliferation of the frontonasal process.

[citation needed] Between the 4th and 8th week of pregnancy, the nasomedial and maxillary processes will fuse to form the upper lip and jaw.

A failure of the fusion between the median and lateral palatine processes results in a cleft palate.

Different mutations can occur in the ALX3 gene, but they all lead to the same effect: severe or complete loss of protein functionality.

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.

[10] The main diagnostic tools for evaluating FND are X-rays and CT-scans of the skull.

Furthermore, disorders like an intracranial cyst can affect the frontonasal region, which can lead to symptoms similar to FND.

It is a triad of developmental defects of the face, comprising midline cleft of the upper lip, nasal and facial skin polyps and central nervous system lipomas.

The severe group presents with a complete cleft of the upper lip and alveolar ridge.

The large variety in phenotypes make the Pai syndrome difficult to diagnose.

Acromelic frontonasal dysplasia is associated with central nervous system malformations and limb defects including a clubfoot, an underdeveloped shin-bone, and preaxial polydactyly of the feet.

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.

[16] Craniofrontonasal dysplasia (CFND) is a rare type of FND with X linked inheritance.

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".

[17] The diagnosis of OAVS is based on the following facial characteristics: microtia (underdeveloped external ear), preauricular tags, facial asymmetry, mandibular hypoplasia and epibulbar lipodermoids (benign tumor of the eye which consists of adipose and fibrous tissue).

[20] It is known that maternal diabetes plays a role in developing malformations of craniofacial structures and in OAVS.

[17] Because newborns can breathe only through their nose, the main goal of postnatal treatment is to establish a proper airway.

[21][22] To correct the rather prominent hypertelorism, wide nasal root and midline cleft in FND, a facial bipartition can be performed.

Complications of this procedure are: bleeding, meningitis, cerebrospinal fluid leakage and blindness.

However, possible risks are rejection, infection, migration of the implant, or unpredictable changes in the physical appearance in the long term.

Orthognathic surgery engages in diagnosing and treating disorders of the face and teeth- and jaw position.