DISCUSSION
In patients with ARS it is described (9)
that 43% showed dental abnormalities and 24 % had facial anomalies but
not all patients show the same manifestations of abnormalities and
anomalies. The different clinical presentation is probably due to
pleiotropic genes affecting the tissues derived from neural crest cells
(16), making it a morphologic and
heterogeneous syndrome. There are many different strategies and opinions
on the timing and planning for correction of the skeletal anomalies and
missing teeth, this force individual planning in each patient.
In the literature there is, in general an agreement on the importance of
a specialized team for planning and treatment each individual patient,
due to ARS being a syndrome with a wide phenotypic heterogeneity.
Early diagnosis and treatment planning both concerning the dentofacial
appearance and function but also more crucial diagnosing systemic
abnormalities. Missing or delaying diagnosis of abnormalities in the
ocular aspect could increase the risk of a patient to become blind due
to missing prophylaxis and/or postponed initialized treatment. The
diagnosis is made based on the clinical and ophthalmologic examination,
and if ARS is suspected a genetic analyze can be performed.
The treatment plan is depending on a good interdisciplinary team of
ophthalmologist, geneticist, maxillofacial surgeon, orthodontist and
prosthodontist, working as a highly specialized team. Relative to the
dentofacial deformity, early treatment in childhood or early
adolescence, in terms of adaptive growth treatment, eg. Hugo De Clerck
type of treatment could possibly benefit the patients
(17).
GeneticsGenetic loci have been described to have association with ARS: FOXC1,
Forkhead box protein C1, on chromosome 6p25. PITX2, Pituitaryn Homeobox
2, on chromosome 4q25. PAX6, on chromosome 11. A fourth locus had been
found on chromosome 13q14 but the gen is not identified yet
(2).
FOXC1 mutations are often associated with patients with ocular
abnormalities, hearing and heart defects
(10), 50-75% of patients with the
mutation will develop glaucoma (18).
There is 54 known mutations of FOXC1 gene including missense (n=31),
nonsense (n=6) and deletions, duplications, frameshift, insertions
(n=17) (19). The mutations alter the
function of FOXC1 by alteration in the gene structure, nuclear
localization, DNA-binding capacity, transactivation activity,
DNA-binding specify and protein stability. Point mutations are found to
be the most common (20).
PITX2 mutations are associated with ocular and systemic abnormalities
(10). PITX2 is an activator for genes
(DIX2) that are essential in teeth and craniofacial development
(5, 10).
There is 87 known mutations of PITX2 gene including missense (n=33),
nonsense (n=10), splice-site (n=6) and deletions/insertions/duplications
(n=38) (1). The expression and function of
FOXC1 and PITX2 is collected in Table 5 due to
(21), (22)
(2) found that 40 % of the patients had a
mutation in PITX2. A mutation in PITX2 and FOXC1 is estimated to be
responsible for 40% of the cases of ARS
(10). As stated earlier in table 3 there
is a correlation between the mutations and the type of ARS.