MAJOR SYNDROMES IN DENTO FACIAL ORTHOPEDICS

MAJOR SYNDROMES IN DENTO FACIAL ORTHOPEDICS

1.INTRODUCTION

• The development of craniofacial structures involves mechanisms whose complexity we are beginning to understand. 
• Alteration of the craniofacial mass in its various tissue components, particularly bone, results in craniofacial malformations which are divided into: Clefts, Dysostosis and Synostosis 
• Knowing the causes of these malformations makes it possible to highlight, as far as possible, the gene responsible first, but also and above all to understand how this altered gene can lead to a deviation in growth and physiological development.

2. DEFINITION 

2-1-Definition of a syndrome

Greek: Sindrome : competition or meeting

Collection of a group of symptoms that occur at the same time in a number of diseases

2-2-Definition of genetics

from the Greek genno = to give birth

Genetics is the science that studies the chemical functions inherent in a particular type of molecule called a gene. One of its branches, formal or Mendelian genetics, is interested in the transmission of hereditary characteristics between parents and their descendants.

3. MAJOR SYNDROMES IN ODF 

3.1. CONGENITAL DISORDERS

3.1.1. Cleft lips

FLPs are the most common craniofacial malformations in humans. They can be part of the clinical picture of many syndromes. They are considered to be of polyfactorial origin. They are more frequent in isolated or non-syndromic form (70 to 95%). 

These are developmental anomalies of the upper maxillary region appearing during embryogenesis, they correspond to a solution of continuity, either at the level of the upper lip, or at the level of the soft palate, or at the level of the maxilla, or at the level of all these structures at the same time (in the most serious cases, the cleft extends from the nostril to the pharynx, thus describing the following elementary varieties:

• Cleft lip : it affects the upper lip, sometimes up to the nostril threshold. The nasal wing is spread out. The alveolus is preserved.
• Cleft lip and alveolar cleft: this involves the upper lip with a crack in the alveolar region or even the entire primary palate. The cleft is usually located in the area of ​​the lateral incisor germ. Oral-nasal communication is rare and occurs at the level of the primary palate. Dental eruption may be altered as a result.
• Velar cleft : it can extend from the uvula to the posterior edge of the bony palate. The minimal form is bifidity of the uvula. Complete velar cleft is accompanied by muscular incompetence of the velum, nasal discharge during swallowing and later by rhinolalia. This cleft can be submucosal visible only on careful examination.
• The velo-palatine cleft : it involves the soft palate and the bony palate up to the incisive foramen (secondary palate) and exposes the vomer. This cleft constitutes a large bucco-nasal communication.
• Mutations in genes such as TWIST and FGFR2 cause severe syndromic craniofacial anomalies.
• Several defective genes have been studied and linked to orofacial clefts (TGFa, TGFb, MSX1, MSX2, RARa…) with variable allelic associations and penetrances.
• In humans, several teratogens have been linked to the appearance of facial clefts: tobacco, alcohol, retinoids, aminopterin, diphenylhydantoins, trimethadione, thalidomide
• This multifactorial nature also makes genetic counseling to parents difficult and empirical. A model for estimating the familial risk of recurrence of the malformation was proposed by Tolarova; it remains only indicative and must be modulated by variables such as sex, race, severity of the condition and environmental factors. 

MAJOR SYNDROMES IN DENTO FACIAL ORTHOPEDICS

4.1.2. VAN DER WOUDE syndrome.

It is characterized by small depressions (or fistulas) of the lower lip, of variable depth, associated or not with a cleft lip, lip-palate or palate. It is the most common syndrome with orofacial cleft: its prevalence in the general population is approximately 1 case in 60,000. Hypodontia can be associated with VWS. The clinical picture can be very variable, even within a family, with all possible combinations, but lip depressions are present in 88% of cases. This syndrome is transmitted in an autosomal dominant manner, with a high penetrance (80 to 97%). Mutations of the IRF6 gene (locus 1q32-q41) have recently been implicated in VWS. More than 70 mutations have been reported, affecting the functioning of the transcription factor IRF6 (interferon regulatory factor 6). Differential diagnoses are faciogenitopopliteal syndrome (poplitealpterygium syndrome) and orofaciodigital syndrome, in which paramedian labial pits are sometimes found, although highly suggestive of Van der Woude syndrome. Treatment of VWS malformations mainly involves repair of the orofacial cleft. Labial fistulas are usually asymptomatic but their surgical excision may be recommended for aesthetic reasons, or to reduce excessive salivation. 

MAJOR SYNDROMES IN DENTO FACIAL ORTHOPEDICS

Clinical signs 

4.1.3. Crouzon syndrome

Crouzon’s disease combines craniosynostosis and facial hypoplasia. Craniosynostosis is variable, but more often than not several sutures are involved. Facial dysmorphism is characteristic with hypertelorism, exorbitism (linked to the double recession of the upper jaw and forehead) and inversion of the dental articulation. An important element is that cranial synostosis is progressive: usually barely or not visible at birth, it appears around the age of 2 years and gradually worsens. However, there are early, congenital forms in which upper jaw hypoplasia is very significant and responsible for breathing difficulties and major exorbitism that can threaten the eyeballs due to lack of palpebral occlusion. These forms may represent a separate entity. Hydrocephalus is frequently observed in Crouzon’s disease, and can pose difficult therapeutic problems. 

It is an autosomal dominant syndrome, for which a mutation of the FGFR2 gene is found in 60% of patients tested. A particular form is also linked to a specific mutation (Ala 391 Glu) in the transmembrane domain of another protein of the same family, FGFR3. The risk of intracranial hypertension (with its major consequence, blindness) is particularly high, threatening two out of three patients, hence the need for surgery.

Clinical signs:  

• Very common
  • Turricephaly/oxycephaly/acrocephaly 
  • Brachycephaly/flat occiput 
  • Craniosynostosis 
  • Hypertelorism 
  • Exophthalmos 
• Frequent
  • Retrognathism/micrognathism 
  • Bird’s beak nose 
  • Prominent lips 
  • Gothic/narrow palace 
  • Badly implanted teeth 
• Casual
  • Domed forehead/frontal bumps 
  • Mandible partial absence/hypoplasia
  • Strabismus 
  • Thin/retracted lips
  • Macroglossia 
  • Anodontia/Oligodontia 

MAJOR SYNDROMES IN DENTO FACIAL ORTHOPEDICS

Teleradiographic examination:

4.1.4. APERT syndrome 

This is a major malformation, associating faciocraniostenosis and bony and membranous syndactyly of the four extremities. Its incidence is 1 in 50,000 births. Craniosynostosis, visible from birth, is always bicoronal. The longitudinal system (metopic and sagittal sutures) is abnormally wide, even during the first months of life. The upper jaw is very hypoplastic, with inversion of the dental articulation, and the face is wide, with a beaked nose, constant hypertelorism and sometimes significant exorbitism. Syndactyly of the fingers and toes can be total (mitten appearance of the extremities) or partial, affecting the second, third and fourth fingers. Mental impairment is extremely frequent and often severe, often associated with cerebral malformations. The vast majority of patients (over 98%) have one of the two adjacent mutations (Ser252Trp and Pro253Arg) of the FGFR2 gene (for fibroblast growth factor receptor type). The insertion of Alu elements in or near exon 9 of this same gene is the cause in the other cases. The risk of intracranial hypertension is high, approaching 50% of cases. Early intervention on craniosynostosis (before the age of 6 months) can improve the mental prognosis.

MAJOR SYNDROMES IN DENTO FACIAL ORTHOPEDICS

• Frequent
  • Fontanelle: large/delayed closure 
  • Hypertelorism 
  • Antimongoloid palpebral fissure
  • Strabismus 
  • Gothic/narrow palace 
  • Convulsions epilepsy 
• Casual
  • Thin nose 
  • Choanal atresia 
  • Cleft palate 

4.1.5. PFEIFER syndrome

Syndrome combining craniosynostosis and partial syndactyly of the hands and feet. 

It affects 1 in 100,000 individuals with autosomal dominant transmissions, 

 It can be caused by mutations in the FGFR-1 or FGFR-2 (fibroblast growth factor receptor) genes.

Clinical signs:

Casual 

• Flat face 
• Asymmetrical face (no facial paralysis) 
• Prognathism 
• Mouth permanently half-open 
• Philtrum court 
• Gothic/narrow palace 

4.1.6. BINDER syndrome

It is a maxillonasal dystosis (naso-maxilo-vertebral syndrome):

This syndrome appears to be abnormally transmitted on the X chromosome.

Teleradiographic signs:

MAJOR SYNDROMES IN DENTO FACIAL ORTHOPEDICS

4.1.7. The FRANCESCHETTI and ZWAHZEN syndrome (from Treacher Collins)

Treacher Collins syndrome (or Franceschetti-Klein syndrome) is a genetic condition that is transmitted in an autosomal dominant manner with a penetrance of 90% and variable expressivity. Its incidence is estimated at 1/50,000 births. This syndrome combines: hypoplasia of the auricles (77%), atresia of the external auditory canals (36%), an anomaly of the ossicular chain, conductive deafness (40%); hypoplasia of the malar and zygomatic bones (80%) with anti-Mongoloid obliquity of the palpebral fissures; coloboma of the lower eyelids (69%) with absence of eyelashes of the outer 1/3 of the lower eyelid; mandibular hypoplasia (78%); cleft palate (28%). Facial malformations are bilateral and asymmetrical. Intelligence is generally normal. Breathing difficulties may occur early due to the narrowness of the upper airways. Deafness should be detected as early as possible.

 The rate of new mutations was estimated at 60% but it would actually be lower according to recent molecular studies. The gene is located on chromosome 5q32-q33.1. 

Clinical signs:

• Very common 
  • Antimongoloid palpebral fissure
  • Flat orbital rim 
  • Retrognathism/micrognathism 
  • Pointed chin 
• Frequent 
  • Prominent nose root 
  • Gothic/narrow palace 
• Casual 
  • Microphthalmia 
  • Choanal atresia 

4.1.8. First arch syndrome or Oto-mandibular syndrome

MAJOR SYNDROMES IN DENTO FACIAL ORTHOPEDICS

4.1.9. Goldenhar syndrome

Goldenhar syndrome or oculo-auriculo-vertebral dysplasia (OAV) is characterized by asymmetrical facial hypoplasia associated with ocular anomalies (dermoid or epibulbar lipodermoid, microphthalmia, coloboma of the upper eyelid, etc.), appendages or preauricular sinuses and vertebral malformations (cervical fusion, vertebral puzzle, etc.). Facial involvement is generally unilateral, but can be bilateral with a more severe expression on one side. Other malformations are reported in 50% of cases: cardiac, cerebral, renal, gastrointestinal anomalies. Mental retardation is present in only 10% of cases. There is a risk of obstructive sleep apnea. The prevalence of OAV dysplasia is estimated at between 1/5,600 and 1/20,000 births. Most cases are sporadic and the risk of empirical recurrence is low (2-3%). In familial cases, the mode of transmission is compatible with autosomal dominant inheritance. OAV dysplasia appears as a complex embryonic developmental field defect.

• Clinical signs:
  • Very common 
    • Narrow face 
    • Retrognathism/micrognathism 
    • Mandible partial absence/hypoplasia 
    • Cleft palate 
    • Macrostomia/large mouth 
    • Conductive/conductive hearing loss 
    • Vertebrae size/shape abnormality 
  • Frequent 
    • Facial paralysis 
    • Flat cheekbones/malar hypoplasia 
    • Lateral cleft lip 

4.1.10. Achondroplasia

Achondroplasia is the most common chondrodysplasia and affects one in 15,000 children. It is characterized by short stature with short limbs, hyperlordosis, short hands, macrocephaly and a high forehead with a marked nasal saddle. This disorder is responsible for a fairly severe height deficit (final height 130cm +/- 10cm) and moderate skeletal deformities, hyperlordosis, and sometimes neurological complications related to the narrowness of the spinal canal. Intellectual development is normal. Diagnosis is based on radiological examination. This condition is transmitted according to an autosomal dominant trait. However, approximately 90% of affected people are born to healthy parents: this is a new mutation, i.e. a genetic accident. The gene responsible is FGFR3 which codes for a fibroblast growth factor receptor expressed in growth cartilage. This is a unique mutation identifiable by molecular study. Antenatal diagnosis is possible. To date, the only therapeutic possibilities are orthopedic. 

Clinical signs:

• Very common 
  • Macrocephaly 
  • Domed forehead/frontal bumps 
  • Flat nose 
  • Depressed nose root
  • Micromelia (normal structure) 
  • Short stature / dwarfism 
  • Autosomal dominant transmission 
• Frequent 
  • Face medium floor of reduced height
  • Small/triangular nostrils 
  • Short hands/brachydactyly

4.1.11. Down syndrome

It is a chromosomal abnormality defined by the presence of a 3rd copy, in whole or in part, of chromosome 21. Down syndrome is not a rare abnormality, but its incidence at birth has decreased significantly in several countries, after the introduction of prenatal screening. Variable intellectual disability, often mild, muscular hypotonia and almost constant joint laxity are the usual consequences, often accompanied by morphological signs and a risk of complications, justifying appropriate monitoring. The morphological particularities (palpebral fissures up and out, epicanthus, flat neck, round face, small nose, single bilateral palmar crease) can be discreet and are not pathognomonic. The main malformations and possible complications include: cardiac and digestive malformations (duodenal atresia), congenital cataracts, Hirschsprung’s disease, short stature, West syndrome, epilepsy, leukemia, sleep apnea, sensory deficits, autoimmune and endocrine pathologies (hypothyroidism, gluten intolerance, diabetes, alopecia), earlier aging and Alzheimer’s disease. In 95% of cases, it is a free (by meiotic non-disjunction) and homogeneous trisomy 21; it is mosaic in 2-3% of cases. Finally, in 2-3% of cases, it is non-free, that is to say that the chromosome or the part of the supernumerary chromosome 21 is integrated into another chromosome. The karyotype allows the diagnosis to be made. For parents of a child with free trisomy 21, the risk of recurrence is little changed (1% up to age 40, linked to maternal age thereafter). In the case of non-free trisomy 21, the risk only increases if one of the two parents is a carrier of a balanced anomaly. For a person with trisomy 21, the risk of transmission is 1/3. The median life expectancy is now over 50 years. 

Clinical signs  :

• Very common 
  • Brachycephaly/flat occiput 
  • Flat face 
  • Mongoloid palpebral fissure 
  • Depressed nose root
  • Ligament hyperlaxity 
  • Short hands/brachydactyly
  • Short foot / brachydactyly toes 
  • Mental/psychomotor retardation
  • Hypotonia 
  • Total/partial trisomy or monosomy 
• Frequent 
  • Fontanelle: large/delayed closure 
  • Short nose/small nose 
  • Flat nose 
  • Microstomia/small mouth 
  • Thick lips 
  • Drooping corners of the mouth 
  • Mouth permanently open 
  • Macroglossia 
  • Gothic/narrow palace 
  • Anomaly of the dentition 
  • Total or partial microdontia 

4.1.12 Moebius syndrome 

• Moebius syndrome is a congenital paralysis of the muscles of the eyes and face.
•  The first symptom is difficulty in suckling. Newborns may also drool excessively and have a strabismus. Then, the absence of facial expression (especially smiling), and the absence of blinking and lateral eye movements dominate the clinical picture. 
• Moebius syndrome is due to a developmental abnormality of the 7th cranial nerve (facial) in all cases, and in 75% of cases of the 6th (abducens). Other cranial nerves may be affected more occasionally (notably the 3rd, 4th, 5th, 9th, 10th and 12th). 
• Most cases are sporadic with no particular family history. 
• Autosomal dominant transmission 

Clinical signs:

Very common 

• Facial paralysis 
• Agenesis of cranial nerve nuclei.

Casual 

• Retrognathism/micrognathism 
• Submucous cleft/bifid uvula 
• Prominent lips 
• Microglossia/aglossia 
• Gothic/narrow palace 
• Total or partial microdontia 
• Email anomaly 

4.2. ACQUIRED CONDITIONS

4.2.1. Acromegaly

Acromegaly is the result of an increase in the secretion of growth hormone (somathormone GH) by the pituitary gland. This increase in secretion is usually secondary to a benign tumor of the pituitary gland (pituitary adenoma).

It is a rare disease, affecting about 40 people in a million, mainly women aged 30 to 40.

Clinical signs:

• Exaggerated growth of the hands.
• Progressive mandibular prognathism.
• Abnormal development of the tongue.
• Macro rhinitis.
• Very open sella turcica

MAJOR SYNDROMES IN DENTO FACIAL ORTHOPEDICS

4.2.2. Temporomandibular ankylosis

Most often due to condylar anatomical lesions with more or less complete fusion of the bony articular surfaces and lesion of the condylar cartilage associated with severe functional disorders with considerable limitation and sometimes total absence of mandibular play when it is symmetrical, it is responsible for class II by brachymandibulia.

4-3-CLINICAL SYNDROMES SECONDARY TO NEUROMUSCULAR BEHAVIORAL ABNORMALITIES 

4-3-.1. The Pierre-Robin syndrome

• Pierre-Robin syndrome or better, the Pierre Robin sequence, is defined by an orofacial morphological triad made up of Retrognathism, Glossoptosis and a median posterior cleft palate. Posterior cleft palate is a defect in the closure of the secondary palate, linked to the persistence of the tongue in a vertical position and to a defect in mandibular development. This anomaly in mandibular development is of varied origin, rarely primitively bony, most often secondary to antenatal orofacial hypomobility, generally due to a defect in the functioning of the primitive brain stem (rhombencephalon). This explains the frequency and severity of neonatal functional signs, namely sucking-swallowing-ventilation disorders, with difficult feedings, choking, esophageal motility disorders, glossopharyngeal-laryngeal ventilatory obstruction, vagal discomfort. 
• The Pierre Robin sequence is isolated in about 50% of cases (no other malformation is associated with it). In these isolated forms, there are about 10% of familial cases. 
• No gene has been isolated to date. 
•  A specialized genetic consultation is recommended even in apparently sporadic cases. 

Clinical signs:

• Very common 
  • Retrognathism/micrognathism 
  • Cleft palate 
  • Glossoptosis 
• Frequent 
  • Pharynx abnormality/swallowing abnormality 
  • Respiratory distress

• Submucosal cleft/bifid uvula 
• Prominent lips 
• Microglossia/aglossia 
• Gothic/narrow palace 
• Total or partial microdontia 
• Delayed bone age 
• Delayed puberty/hypogonadism 
• Mental/psychomotor retardation
• Abnormal nerve conduction 
• Short stature / dwarfism.

4-3-.2. Rix syndrome:

It is a behavioral abnormality of the oro-labial area determined by the abnormal shaping action of the oro-buccal sphincter during infantile “refuge” sucking. The child sucks abnormally, sucking dominates the situation.

• in the affective and emotional child a characteristic mimicry renewing itself at each period of worry, 
• sucks his cheek and lip greedily.
• the muscles of the lips and chin are strongly contracted, supported by the cheeks at the corners, acting strongly on the alveolar process.

Clinical examination:

• Atypical swallowing
• Pathological tilt of the lingual mass 
• “functional retrognathia”:
• the lumen of the pharynx modified by the malposition of the lingual mass.
• The mandible is poorly developed.
• Retroalveolus <accompanying open bite or superior proalveolus.
• Normal profile.

Teleradiographic examination:

• Lingual mass in its resting position leaves the pharynx wide open.
• This essential element + normal position of the mandible confirms the syndrome

5-3-.3. Eschler syndrome (Cauhépé Fieux)

• It is an anomaly of lingual position determined by a mimic of refuge with lateral dominance.
• Suction linguo-mandibulo-hyoid imbalance:

Lateral interposition of the lip and tongue and swallowing becomes pathological.

Clinically: 

• Deviation of the lower face associated with occlusion disorders.

Mandibular play:

• Swing deviated to the side of the tongue. 
• Mandible of normal shape.
• Crossed lateral joint right or left
• Deviation from the closing path

6. Conclusion

Given the complexity and clinical and symptomatological variability of these congenital and acquired malformations , it seems essential for the orthodontist to know the etiology of their occurrence and the mode of transmission of congenital conditions, in order to overcome the anomalies associated with them and above all to prevent their occurrence for subsequent generations.

Also, since genetic expression cannot be modified, the presence of a hereditary factor heavily influences the treatment plan and the specific prognosis of patients presenting one or other of the malformations. 

MAJOR SYNDROMES IN DENTO FACIAL ORTHOPEDICS

  Cracked teeth can be healed with modern techniques.
Gum disease can be prevented with proper brushing.
Dental implants integrate with the bone for a long-lasting solution.
Yellowed teeth can be brightened with professional whitening.
Dental X-rays reveal problems that are invisible to the naked eye.
Sensitive teeth benefit from specific toothpastes.
A diet low in sugar protects against cavities.
 

MAJOR SYNDROMES IN DENTO FACIAL ORTHOPEDICS