INTERDISCIPLINARY

Anomaliile cromozomiale şi defectele orodentare – diagnosticul prenatal

 Chromosomal disorders and oro-dental defects – prenatal diagnosis

Andrei Kozma, Viorica Radoi, Radu Ursu, Dona Andreea Iordan-Dumitru, L.C. Bohîlțea

First published: 21 mai 2019

Editorial Group: MEDICHUB MEDIA

DOI: 10.26416/Gine.24.2.2019.2378

Abstract

Genetic disorders can be classified as single gene inhe­ri­tance, multifactorial inheritance, chromosome ab­nor­ma­li­ties and mitochondrial inheritance. Every congenital struc­tural defect in the body represents an inborn error in morphogenesis and may affect one or more systems. Cur­rently, craniofacial abnormalities can be detected by mo­dern ultrasound examination as early as at 16 weeks of ges­ta­tion. Several chromosomal disorders, numerical and struc­tu­ral as well, include oro-dental defects among their cli­ni­cal symptomatology. The severity of these disorders vary widely from extremely severe to mild, but oral defects are present in all. Chromosomal disorders and syndromes often arise from numerical and structural defects of the chro­mo­somes, leading to various manifestations, some of which also include the craniofacial region. Genetics and its understanding and applications enhance our abi­li­ty to understand the growth and development of cra­nio­fa­cial structures, leading to the early intervention and pre­ven­tion of disease onset. Knowledge of the genetic al­te­ra­tions that may cause oro-dental defects allows the ge­ne­tic examination, the prenatal diagnosis and counselling of future parents with traits of oral cleft in the family.

Keywords
oro-dental defects, prenatal diagnosis, chromosomal disorders

Rezumat

Tulburările genetice pot fi clasificate ca moştenire genetică uni­că, moştenire multifactorială, anomalii cromozomiale sau moştenire mitocondrială. Fiecare defect congenital structural din organism reprezintă o eroare înnăscută în morfogeneză şi poate afecta unul sau mai multe sisteme. În prezent, anomaliile cra­nio­faciale pot fi detectate de examenul ultrasonografic mo­dern încă de la 16 săptămâni de gestaţie. Mai multe tul­bu­rări cromozomiale, numerice şi structurale, includ defecte oro­den­ta­re prin simptomatologia lor clinică. Severitatea aces­tor tul­bu­rări variază foarte mult, de la extrem de severe la uşoa­re, dar defectele orale sunt prezente la toate. Tulburările şi sin­droa­me­le cromozomiale apar adesea din defectele numerice şi structurale ale cromozomilor, ceea ce conduce la manifestări va­ria­te, dintre care unele includ şi regiunea craniofacială. Ge­ne­ti­ca şi înţelegerea ei, precum şi aplicaţiile sale sporesc abi­li­ta­tea noastră de a înţelege creşterea şi dezvoltarea structurilor cra­nio­fa­ciale, conducând nu numai la o intervenţie timpurie, ci şi la pre­ve­ni­rea declanşării bolii. Cunoaşterea modificărilor genetice care pot provoca defecte orodentare este posibilă datorită exa­mi­nă­rii genetice şi diagnosticului prenatal şi permite consilierea viitorilor părinţi ce vor avea urmaşi cu despicături orale în fa­milie. 

Background

Genetic disorders can be classified as single gene inheritance, multifactorial inheritance, chromosome abnormalities and mitochondrial inheritance.

The medical management of individuals with syndromes affecting craniofacial and dental structures is mostly accomplished by an interdisciplinary team from early childhood on.

Structural morphogenetic defects – definitions
 

Figure 1. Types of inborn errors of morphogenesis(1)
Figure 1. Types of inborn errors of morphogenesis(1)

Every congenital structural defect in the body represents an inborn error in morphogenesis and may affect one or more systems. In general, most congenital anomalies can be divided into four types (Figure 1)(1):

a) Disruptions: a rare anomaly related to breakdown of the original normal foetal developmental process – e.g., craniofacial cleft resulting from amniotic bands.

b) Deformations: these occur secondary to mechanical forces, leading to anomalies of a lesser degree when compared to disruption – e.g., club foot, cleft palate, Pierre Robin sequence etc.

c) Malformations: a morphologic defect in an or­gan from an intrinsically abnormal developmental process – e.g., polydactyly, congenital heart anomalies, cleft lip etc. 

d) Dysplasia: an abnormal growth or development of a specific tissue or organ.

Genetic changes

The chromosomal abnormalities can be due to alterations in the number or structure of the chromosomes.

The chromosomal anomalies typically arise from alterations in the DNA containing chromosomal regions and can be reliably detected by karyotype analysis(1,2,3).

Karyotyping is the basic tool of cytogenetic studies and most commonly involves G banding staining technique.

a) Numerical abnormalities

The most frequently reported numerical abnormalities are aneuploidies which may be due to either nondisjunction or anaphase lag (Figures 2 and 3)(3,4).
 

Figure 2. Meiotic nondisjunction(3)
Figure 2. Meiotic nondisjunction(3)
Figure 3. Anaphase lag(4)
Figure 3. Anaphase lag(4)

b) Structural chromosomal abnormalities

Structural abnormalities are mostly caused spontaneously by loss or rearrangement of the chromosomal material(4).
 

Figure 4. Human chromosome morphology(9)
Figure 4. Human chromosome morphology(9)

Chromosomal disorders and syndromes often arise from numerical and structural defects of the chromosomes, leading to various manifestations, some of which also include the craniofacial region.

Genetics and its understanding and applications enhance our ability to understand the growth and development of craniofacial structures, leading to the early intervention and prevention of disease onset(2,4-6). Dental health caregivers should be aware of the technological and scientific improvements in the field of genetic testing and at the same time have ethical restraints over unrealistic expectations from it(2,7,8).

Several chromosomal disorders, numerical and structural as well, include oro-dental defects among their clinical symptomatology (Table 1)(10-50). The severity of these disorders vary widely from extremely severe to mild, but oral defects are present in all.
 

Table 1. Chromosomal disorders with oro-dental defects
Table 1. Chromosomal disorders with oro-dental defects
Table 1. Chromosomal disorders with oro-dental defects (cont.)
Table 1. Chromosomal disorders with oro-dental defects (cont.)

Discussion

The development of novel clinical therapies for orofacial and dental pathological conditions depends very much on a detailed knowledge of the molecular and cellular processes that are involved in head formation.

c) Clinical relevance of genetic findings

Currently, craniofacial abnormalities can be detected by modern ultrasound examination as early as at 16 weeks of gestation(2,51). In oral clefts, which are particularly relevant to clinical dentistry, the only therapy available for the closure of the cleft(s) is the surgical intervention. The identification of the molecular players and the unraveling of the genetic pathways that dictate palatogenesis and lip formation could offer new and exciting possibilities for the prevention and therapy of orofacial defects(1-8,51).

The knowledge of the genetic alterations that may cause oro-dental defects allows the genetic examination, prenatal diagnosis and the counseling of future parents with traits of oral cleft in the family.

Conclusions

The control of genetic diseases should be based on an integrated and comprehensive strategy combining the best possible treatment and prevention through community education, population screening, genetic counseling, and the availability of early diagnosis.

Genetic counseling will encompass legal and psychosocial management issues related to genetic screening, privacy and confidentiality, disclosure of unexpected and unwanted findings, and obligations to identify and communicate difficult issues.  

 

Compliance with ethics requirements:

The authors declare no conflict of interests regarding this article. The authors declare that all the procedures and experiments of this study respect the ethical standards in the Helsinki Declaration of 1975, as revised in 2008, as well as the national law. The informed consent was obtained from the patient included in the study. No funding for this study.

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