The major syndromes in ODF:
- Introduction :
The etiology of orthodontic anomalies poses daily the problem of the hereditary incidence determining considerably the treatment plan and the prognosis (knowing that the genetically predefined anomalies are more difficult and the prognosis reserved). Thus oral genetics is a discipline which arouses more and more interest for the orthodontist particularly for the management of patients suffering from syndromes requiring a multidisciplinary treatment.
- Definition :
- Syndrome: A group of symptoms that occur together in a number of diseases.
- Genetic disease disease due to the deficiency of one or more genes (one can have it without the parents being sick).
- Hereditary diseases diseases transmitted by genetic mechanism from parents to offspring.
- Congenital disease is a pathological condition that exists at birth and may be due to genetic abnormalities, the intrauterine environment, or unknown factors.
- Craniosynostosis (stenosis=closure): congenital malformation consisting of the premature closure of the sutures of the different parts of the cranium.
- Dysplasia: malformation or deformation resulting from an abnormality in the development of a tissue or organ.
- Dysostosis: bone development disorder.
- Chondrodysplasia: A disorder of cartilage development (chondro-) resulting in morphological abnormalities and bone development disorders. Synonym: chondrodystrophy.
- Achondroplasia: congenital bone disease causing dwarfism.
- Chromosomal aberrations : These are abnormalities in either the number or structure of chromosomes. They are sometimes detected before birth by karyotype analysis of cells from the fetus. These are obtained by trophoblast puncture or amniocentesis (sampling of amniotic fluid during pregnancy).
*The presence of excess chromosomes is trisomy.
*A missing chromosome in a pair constitutes a monosomy.
The major syndromes in ODF:
May be genetic, acquired or secondary to a neuromuscular behavior disorder (NMD)
- Cleft lip and palate
- Binder syndrome
- Crouzon syndrome
- FRANCESCHETTI and ZWAHZEN syndrome (by Treacher Collins)
- Apert Syndromes (Acrocephaly Syndactyly)
- First arch syndrome or Oto-mandibular syndrome
- Chondrodysplasia (Achondroplasia)
- Down syndrome (trisomy 21)
- Unilateral hypercondylia in adults
- Vander Woude syndrome (VWS):
- Characteristics: Characterized by small depressions (or fistulas) of the lower lip, of variable depth, associated or not with a cleft lip, lip and palate or palate. Hypodontia may 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.
Its prevalence in the general population is approximately 1 case in 60,000.
This syndrome is transmitted in an autosomal dominant manner.
Mutations in the IRF6 gene (locus 1932-241) have recently been implicated.
Major syndromes in ODF
- Clinical signs:
- Very common: Fistula of the labia
- Common: Lateral cleft lip; Cleft palate
- Occasional: Anodontia/oligodontia.
- Crouzon syndrome:
- Characteristics : Crouzon disease combines craniosynostosis and facial hypoplasia. Craniosynostosis is variable, but most often several sutures are involved.
It is an autosomal dominant syndrome, for which we find:
Incorporation of the atlas (vertebra) into the occipital region: disruption of HOX gene expression.
Facial synostoses: interactions between MSX1, MSX2, DLX genes and growth factors are disrupted.
Craniofacial stenosis: Mutations in the FGFR2 (ch. 10q 26) and FGFR3 (ch. 4q 16) genes in the domain of receptors for bone growth factors.
- Clinical signs:
- Very common
Turricephaly (tower-shaped or pointed skull deformity)/oxycephaly (tilted forehead and pointed top of the skull)/acrocephaly (exaggerated height of the skull in the shape of a sugarloaf)
Brachycephaly/flat occiput
Craniosynostosis
Hypertelorism (increased distance between the two eyes)
Flat orbital rim
Exophthalmos
- Frequent
Retrognathism/micrognathism
Bird’s beak nose
Prominent lips
Gothic/narrow palace
Dental malposition.
- Casual
Domed forehead/frontal bumps
Strabismus (eye coordination disorder)
Thin/retracted lips
Macroglossia
Anodontia/Oligodontia
Mental/psychomotor retardation
Posteriorly rotated ears
Atretic/absent external auditory canal
Hearing abnormality/deafness
- The teleradiographic examination:
- Digitizations of the cranial vault.
- Angulation between the antero and posterior part of the base of the skull. The reduction of the latter leads to underdevelopment of the antero third of the face.
- Incorporation of the atlas into the occipital region.
- Upper maxillary hypoplasia;
- Prognathism
- Apert syndrome (acrocephaly, syndactyly=fingers stuck together):
- Features :
It 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.
Autosomal dominant transmission.
The vast majority of patients (more than 98%) have one of the two adjacent mutations of the FGFR2 gene (for fibroblast growth factor receptor type), located on chromosome 10 Locus q26.
Development of the palatine lamina bone and its sagittal suture: Interactions between homeotic genes
MSX1, MSX2 growth factors.
The sagittal suture of the secondary palate undergoes early synostosis.
Major syndromes in ODF
- Clinical signs:
- Very common:
Brachycephaly/flat occiput
Craniosynostosis
Domed forehead/frontal bumps
Flat face
Flat orbital rim
Middle floor of the sunken face
Depressed nose root
Low set ears
Syndactyly of fingers and toes
- Frequent :
Fontanelle: large/delayed closure
Hypertelorism
Strabismus
Gothic/narrow palace
Antimongoloid palpebral fissure (tilt).
Thumb wide
Wide big toe
Trachea abnormality
Nervous system abnormality (structure)
Mental/psychomotor retardation
Convulsions epilepsy
- Casual :
Thin nose
Choanae atresia
Cleft palate
Micromelia (very small cheek)
Joint stiffness
Radioulnar synostosis
Tuberous/cavernous hemangiomas
Esophageal atresia/trachoesoph fistula.
Pyloric stenosis
Anus ectopy / anteposition
Lung aplasia/hypoplasia
Polycystic kidney disease
Uterus/vagina/fallopian tubes abnormality
Congenital heart disease
Ventricular dilation without hydrocephalus.
Corpus callosum/septum pellucidum: agenesis.
Major syndromes in ODF
- Pfeiffer syndrome:
- Features :
Syndrome combining craniosynostosis and partial syndactyly of the hands and feet.
It affects 1 in 100,000 individuals.
Depending on the severity of the phenotype, Pfeiffer syndrome is divided into three subtypes. Classic Pfeiffer syndrome, or type 1 , includes patients who have mild symptoms, such as brachycephaly, centrofacial hypoplasia, and abnormalities of the fingers and toes; patients have normal intelligence, developmental delay, and neurological complications.
Autosomal dominant transmission
It can be caused by mutations in the FGFR-1 or FGFR-2 (fibroblast growth factor receptor) genes.
- Binder syndrome:
It is a maxillonasal dysostosis (nasomaxillovertebral syndrome):
- Features :
- Flattening of the mid-face.
- Nasal hypoplasia with reduction or absence of the nasofrontal angle with absence of the relief of the glabella
- Nearly vertical nasal bone, a high and very oblique philtrum downwards and forwards and the upper lip is thin.
- Premaxillary dysplasia with agenesis of the ENA and submaxillary sectors.
- Flattening of the maxillary arch curve with inversion of the incisor-canine articulation: CL III incisor-canine infraocclusion
- Low position of the tongue, with interposition during swallowing.
- This syndrome appears to be abnormally transmitted on the X chromosome.
- Teleradiographic examination:
- Absence of ENA
- SNA and SNB decreased.
- Increased FMA angle.
- Opening of the goniac angle
- Reduced maxillary base length
- Reduced frontal sinuses
- FRANCESCHIETTI and ZWAHZEN syndrome (from Treacher Collins):
- Features :
This is mandibulofacial dysostosis.
It is a genetic condition that is transmitted in an autosomal dominant manner with a penetrance of 90% and variable expressivity. The rate of new mutations was estimated at 60%.
The gene is located on chromosome 5q32-q33.1.
Its incidence is estimated at 1/50,000 births.
- Clinical signs:
- Very common
Antimongoloid palpebral fissure
Flat orbital rim
Retrognathism/micrognathism
Pointed chin
Eyelid coloboma
Anotia/microtia
- Frequent
Prominent nose root
Gothic/narrow palace
Atretic/absent external auditory canal
Middle ear abnormality
Conductive/conductive hearing loss
- Casual
Microphthalmia
Iris coloboma
Retinoschisis / retinal coloboma
Choanal atresia
Macrostomia/large mouth
Microstomia/small mouth
Preauricular appendages
Preauricular fistulas
Back/spine/pelvis abnormality
Testicle ectopia/cryptorchidism
Congenital heart disease
Mental/psychomotor retardation
- First arch syndrome or Oto-mandibular syndrome:
- Features :
It is a hereditary disease describing bilateral, but most often unilateral, agenesis or hypoplasia of the derivatives of the branchial arch.
Hypoplasia affects all tissues:
- Bone tissue: hypoplasia of the ascending branch, ATM
- Cartilaginous tissue: agenesis of the EAC and the auricle.
- Muscle tissue: agenesis of the masticatory muscles.
- Dermal tissue: hypoplasia of the lateral-facial dermis.
- Nervous tissue: facial paralysis.
Hypoplasia of the ascending ramus is the cause of very frequent dental inclusions or a class II occlusion.
- Goldenhar syndrome:
- Features :
Goldenhar syndrome or oculo-auriculo-vertebral dysplasia (OAV) is characterized by asymmetric facial hypoplasia. Facial involvement is usually unilateral, but may be bilateral with more severe expression on one side.
Mental retardation is present in only 10% of cases.
There is a risk of obstructive sleep apnea (OSA).
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.
Genetic heterogeneity is certain.
Major syndromes in ODF
- Clinical signs:
- Very common
Narrow face
Retrognathism/micrognathism
Mandible partial absence/hypoplasia
Pointed chin
Epibulbar dermoid cysts
Cleft palate
Macrostomia/large mouth
Conductive/conductive hearing loss
Atretic/absent external auditory canal
Preauricular appendages
Vertebrae size/shape abnormality
- Frequent
Facial paralysis
Flat cheekbones/malar hypoplasia
Lateral cleft lip
Cheeks skin buds
Microphthalmia
Astigmatism
Eyelid coloboma
Posteriorly rotated ears
Hearing abnormality/deafness
- Chondrodysplasia or achondroplasia:
- Features :
Achondroplasia is the most common chondrodysplasia and affects one in 15,000 children.
Autosomal dominant transmission. However about 90% new mutation.
The responsible gene is FGFR3 which encodes a fibroblast growth factor receptor expressed in growth cartilage.
- Clinical signs:
- Very common
Short stature / dwarfism
Macrocephaly
Domed forehead/frontal bumps
Flat nose
Depressed nose root
Micromelia (normal structure)
- Frequent
Middle floor of the face of reduced height;
Mandible often normal with an image of prognathism due to underdevelopment of the anterior base of the skull + nasal capsule.
An occlusion often with features of CL III.
Small/triangular nostrils
Vertebrae size/shape abnormality
Narrow iliac wings
Short hands/brachydactyly
- Casual
Joint stiffness
Diaphyses anomaly
Hypotonia.
- Down syndrome: Trisomy 21:
- Features :
It is a chromosomal abnormality defined by the presence of a 3rd copy, in whole or in part, of chromosome 21.
Median life expectancy is now over 50 years.
- Clinical signs:
- Very common
Brachycephaly/flat occiput
Flat face
Mongoloid palpebral fissure
Epicanthus
Depressed nose root
Round ear
Short neck
Excess skin on the neck
Ligament hyperlaxity
Short hands/brachydactyly
Short foot/brachydactyly toes
Mental/psychomotor retardation
Hypotonia
Total/partial trisomy
- Frequent
Fontanelle: large/delayed closure
Short nose/small nose
Flat nose
Microstomia/small mouth
Thick lips
Drooping corners of the mouth
Mouth permanently ajar
Macroglossia
Gothic/narrow palace
Anomaly of the dentition
Total or partial microdontia
Umbilical hernia
Clinodactyly of the 5th finger
Transverse palmar crease
Space between 1st and 2nd toe
Sterility/subfertility
Congenital heart disease
Lymphatic-immune system abnormality
Susceptibility to infections
Mental regression / dementia
Generalized obesity
Early senility/premature aging.
- Casual
Cataract
Myopia
Strabismus
Conductive/conductive hearing loss
Localized hypotrichy (other than vertex)
Small intestine/colon abnormalities
Imperforate anus/rectovaginal fistula.
Unilateral/bilateral kidney agenesis/hypoplasia
Hypothyroidism
Hyperglycemia/diabetes not ins. dep.
Gait disturbances/abnormal gait
Insensitivity pain sensory disturbances
Leukemia.
- HANHART syndrome:
- Features :
This malformation association includes craniofacial anomalies, limb anomalies and other less constant malformations.
Cranial nerves may be affected in the form of Moebius syndrome
Autosomal recessive mutation of a gene.
- Clinical signs:
- Very common
Retrognathism/micrognathism
Mandible partial absence/hypoplasia
Microstomia/Small mouth
Microglossia/aglossia
Gothic/narrow palace
Upper limb transverse anomaly
Oligodactyly of the fingers
Fingers distal phalanx hypoplasia
Foot absence/apodia/adactvlie
Toes distal phalanx hypoplasia
Thin/hypoplastic nails (hands)
- Frequent
Face asymmetry (no facial paralysis)
Telecanthus
Wide nose root
Cleft palate
Anodontia/Oligodontia
Syndactyly of the fingers
Syndactyly of the toes
Cranial nerve nuclei agenesis
- Casual
Conductive/conductive hearing loss
Severe mental retardation
Stillbirth / neonatal death
Maternal diabetes.
Major syndromes in ODF
- Pierre-Robin syndrome:
- Features :
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 mandibular development anomaly is of varied origin, rarely primarily 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 suction-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
- Conclusion :
Genetic diseases are numerous but rare and the clinician will only encounter a small number of them in his daily practice, so his clinical sense will be essential to recognize and detect the signs of each syndrome.
Through his training in genetics, the dental surgeon is able to recognize the oral signs during the examination of the patient. He may also be required in certain cases to be the first to highlight the malformation which will be confirmed by specialized examinations.
Dental crowns are used to restore the shape and function of a damaged tooth.
Bruxism, or teeth grinding, can cause premature wear and often requires wearing a retainer at night.
Dental abscesses are painful infections that require prompt treatment to avoid complications. Gum grafting is a surgical procedure that can treat gum recession. Dentists use composite materials for fillings because they match the natural color of the teeth.
A diet high in sugar increases the risk of developing tooth decay.
Pediatric dental care is essential to establish good hygiene habits from an early age.