Genetic and chromosomal aberrations in children

Genetic and chromosomal aberrations in children
Introduction, Definitions, Classification of genetic disorders, Classification of chromosomal aberrations, Chromosomal abnormalities, Pattern of inheritance, Structural abnormalities, Autosomal dominant conditions, Autosomal recessive conditions, X-linked conditions, Chromosomal syndromes, Polygenic conditions

1. Genetic and chromosomal aberrations in children PART II POST GRADUATES

2. Contents Introduction Definitions Classification of genetic disorders Classification of chromosomal aberrations Chromosomal abnormalities Pattern of inheritance Structural abnormalities Autosomal dominant conditions Autosomal recessive conditions

3. X-linked conditions Chromosomal syndromes Polygenic conditions Conclusion References

4. Introduction Genetic disorders are likely to effect everyone at some time. Some are of more obvious importance than others, depending on the age of the onset of the disease, the degree of mental or physical impairment, the numbers of affected individuals, and the cost of care The dentist often in a unique position to pick up a previously unrecognized genetic or birth defect problem in a patient or family.

5. Definitions Gene : The functional unit of hereditary responsible for the transmission of characters to the progeny or off-springs. Alleles : They are a pair of genes present at a specific locus in homologous chromosomes. Homozygous : Condition where the paired genes are similar on homologous chromosomes for a character. Heterozygous : Condition where the paired genes are dissimilar on homologous chromosomes for a character.

6. Hybrid : It is an offspring of two parents differing in one or more characters. Dominant gene : It is a gene which expresses itself in the presence of a contrasting gene. Recessive gene : It is a gene which fails to express itself in the presence of a dominant gene.

7. Classification Of Genetic Disorders (Dianna M.  Milewicz 2007)

8. Classification Of Chromosomal Aberrations ( Dianna M.  Milewicz 2007)

9. Chromosomal Abnormalities NUMERICAL ABNORMALITIES 1.Polyploidy: chromosomes count exceeds the diploid number and is also an exact multiple of its haploid number. e.g. Triploidy is a condition in which there are three times the no. of haploid chromosomes. . Tetraploidy is a condition in which there are four times the no. of haploid chromosomes. 2.Aneuploidy: the diploid chromosomes number of a cell is not an exact multiple of its haploid number.

10. Autosomal aneuploidy – Trisomy 21(Down’s Syndrome) Trisomy 13( Patau’Syndrome ) Trisomy 18(Edward Syndrome) Sex chromosomal aneuploidy Kleinfelter’s (47,XXY) Turner’s (45,X0) Triple X Syndrome(47,XXX)

11. Non-Disjunction Nondisjunction is the failure of chromosome pairs to separate properly during cell division. This could arise from a failure of homologous chromosomes to separate in meiosis I , or the failure of sister chromatids to separate during meiosis II. When a single chromosome is lost (2n-1), it is called a monosomy . When a chromosome is gained, it is called trisomy , Examples of nondisjunction : Down syndrome, Triple-X syndrome, Klinefelter's Syndrome, Turner's Syndrome, Edward Syndrome, Patau’s Syndrome

12. Pattern Of Inheritance Inheritance is a term used to denote transmission of characters from parents to off springs .

13. Mendelian Inheritance The manner in which genes and traits are passed from parents to their children. Disorders caused by a defect in a single gene follow the patterns of inheritance described by Mendel(1965).

14. Dominant : If a trait or disease manifests itself when the affected person carries only one copy of the gene responsible, along with one normal allele, the mode of inheritance of the trait is called dominant. Recessive : If two copies of the defective gene are required for expression of the trait, the mode of inheritance is called recessive .

15. Autosomal Dominant Disease can be inherited from one parent also. Can affect both males and females Can be traced through many generations of a family. Affected people are heterozygous for the abnormal allele and transmit the gene for the disease to half their offspring, whether male or female .

16. Autosomal Recessive Disease can appear only if both parents transmit it. Unaffected parents can transmit the trait to their offsprings (if both parents carry recessive gene) Siblings may be affected but parents usually are apparently normal Abnormal gene remains suppressed and does not manifest in a heterozygous individual. Affected person is homozygous for the trait.

17. X-Linked Dominant The gene is located on the X chromosome, but the gene acts in a dominant manner. This means that both males and females can display the trait or disorder, by only having one copy of the gene.

18. X-Linked Recessive X-linked recessive genes are expressed in females only if there are two copies of recessive gene (one on each X chromosome). In Males there only needs to be one copy of an X-linked recessive gene in order for the trait or disorder to be expressed. Only males are affected , but can be transmitted through healthy female carriers . A female carrier will transmit the condition to half her sons, and half her daughters will be carriers.

19. An affected male will transmit the defective gene to all his daughters but to none of his sons. This absence of male to male transmission is a hallmark of X linked inheritance. Trait is passed from an affected male to all of his daughters and then to ½ of the daughter’s sons.

20. Multifactorial Inheritance Polygenic inheritance , also known as quantitative or multifactorial inheritance refers to inheritance of a phenotypic characteristic (trait) that is attributable to two or more genes and their interaction with the environment. Unlike monogenic traits, polygenic traits do not follow patterns of Mendelian inheritance.

21. Structural Abnormalities Chromosomal Translocation ROBERTSONIAN TRANSLOCATION : Result from breakage of two accocenteric chromosomes with subsequent fusion of long arms RECIPROCAL TRANSLOCATION : It involves breakage of at least two chromosomes and exchange of fragments.

22. Chromosome Deletion Deletion is the loss of a portion of a chromosome Chromosome Ring It is a deletion chromosome in which both ends are lost and two broken ends unite to form a ring. The size of the ring, depends on how much material was lost and which chromosomes are involved.

23. Chromosome Inversion Inversion is the separation of a portion of a chromosome followed by rearrangement but not in the same order. If the inverted area includes the centromere it is called a pericentric inversion. If it does not, it is called a paracentric inversion.

24. Chromosome Duplication It involves presence of extra segment of chromosome which usually results from unequal crossing over. Duplications are more common and less harmful to the individual than are deletions. Abnormalities of Structure related to sex chromosome Isochromosome X – a long X chromosome – which results from deletion of the short arms of the X chromosome and duplication of the long arm.

25. Autosomal dominant conditions

26. Achondroplasia( Chondrodystrophia fetalis ) Transmitted as an autosomal dominant trait. It is a genetic disorder affecting the growth and development of bone and cartilage Etiology : by Mutation in Fibroblast Growth Factor Receptor - 3 gene ( FGFR3 ) Result in decreased endochondral ossification , inhibited proliferation of chondrocytes in growth plate cartilage, decreased cellular hypertrophy and decreased cartilage matrix production.

27. Common cause of dwarfism Women and men are equally affected Global Incidence : 1 in every 25,000 births . ( Wynn J, King TM, Gambello MJ, Waller DK, Hecht JT (2007 ) In India : 12 in 1000 (Debbie Siegal,2007)

28. Clinical features The head is large and the arms and legs are short when compared to the trunk length. (disproportionally long trunks) Prominent forehead (frontal bossing ) Small midface with a flat nasal bridge and narrow nasal passages (midface hypoplasia) Thoracolumbar protuberance Limitation of joint movement Normal intelligence

29. Oral manifestations Maxillary retrusion Mandibular prognathism (class III malocclusion) Missing teeth may be seen in primary as well as permanent dentition. Crowding Poor oral hygiene

30. Radiographic features Lateral skull radiographs demonstrates Mid face hypoplasia Enlarged calvarias Frontal prominence Shortening of the base of the skull Long bones are shorter then normal Thickening and mild clubbing of the ends Epiphyses generally appear normal but may close either early or late

31. Treatment Growth and weight should be carefully monitored. Head circumference should be carefully monitored. Orthopedic treatment, ENT treatment and neurosurgical procedures may be necessary . Growth-hormone treatment increases the rate of growth during the first year of treatment. Midface deficiency in achondroplasia ideally is accomplished by a Le Fort III osteotomy to move the entire midface forward. Orthodontic treatment to correct malocclusion

32. Treacher Collin’s Syndrome (Mandibulofacial dysostosis) ( also known as Franceschetti- Zwahlen -Klein syndrome ) is a genetic disorder characterized by craniofacial deformities. Inheritance is autosomal dominant Etiology : Change in the Treacher Collins-Franceschetti -1(TCOF1) gene on chromosome 5 . M ales = Females Multiple generations are affected

33. It is named after Edward Treacher Collins (1862–1932), who described its essential traits in 1900. Global Incidence: 1 in 25,000 births (Acc to R Madhan, Sanjna,2006) In India : 1 in 50,000 (Acc to Statistics By Country for Treacher Collin Syndrome,2004 ) More than 50 families have been analyzed Detected mostly around 3-6 years of age

34. Typical craniofacial disorder of 1 st and 2 nd pharyngeal arches Affects the development of arches and produced defects of head and face Caused by fetal vascular anomaly which deprives the first visceral arch of its blood supply between the third and fifth weeks of gestation

35. Clinical features Bird face like or fish like appearance Microphthalmia A ntimongoloid down - slanting palpebral fissures Notched lower eyelids (coloboma) Deficiency of eyelashes Auricle usually in low position and atresia of external auditory meatus (36%) Underdeveloped and malformed ears (77%) Hypoplasia of facial bones, Hypoplastic zygoma(28%) Depressed cheeks and hypoplasia of mandible

36. Other anomalies facial clefts and skeletal deformities Harelip Deafness Large tongue and large irregular upper incisors Dwarfism Defects in brain development as microcephaly , mental retardation and psychomotor delay.

37. Dental findings Hypoplasia of mandible and maxilla) Dysplasia of TMJ and Limited mouth opening Midline deviation Improper tongue position Cleft palate Open bite

38. Impacted Supernumery teeth Small mouth and high palate High plaque index and poor efficacy of tooth-brushing ( acc to gisele da silva dalben lucimara teixeira das neves marcia ribeiro gomide,2008)

39. Radiographic features Malformed auditory ossicles with fusion between malleus and incus Non-fusion of the zygomatic arches as well as absence of the palatine bones Hypogenesis and agenesis of the mandible Paranasal sinus are grossly underdeveloped

40. Treatment after birth At time of birth child with TCS concerns centers – adequacy of airway , swallowing and feeding, hearing, vision, presence of cleft palate Airway may be compromised – maxillary hypoplasia and mandibular hypoplasia May necessitate special infant positioning , extended hospital stay , pulse oximetry monitoring , immediate or delayed tracheostomy or placement of mandibular distractor. If newborn with TCS have difficulty in swallowing – placement of gastrostomy tube

41. Treatment Early childhood program for speech and language stimulation may be recommended. B one-anchored hearing aids in case of hearing problems People with the syndrome undergo surgeries for facial and external ear reconstruction. Surgical closure of the cleft in case of cleft palate. Combined orthodontic therapy along with orthognathic surgery is also sometimes required.

42. Cleidocranial Dysplasia ( Marie-Sainton’s Disease) Congenital disorder of bone formation Etiology : Rearrangement of long arm of chromosome 8 and 6. Mutation in the core-binding factor alpha-1(CBFA-1) gene First described by Meckel and Martin in the mid 8 th century. Global Incidence :1 in 10,00,000 ( I.Golan,2003) In India ,1 in 5100 ( Dhavendra Kumar,2004 ) Reported in all ethnical group No sex predilection

43. Manifested with Hypoplastic or aplastic clavicle with narrow thorax delayed ossification of the skull excessively large fontanelles(brachycephalic skull) delayed closing of suture Midface hypoplasia Short stature

44. Etiopathogenesis Clavicle is first bone to ossify in body in man (5 th week) Clavicle – partially formed in membrane and partially in cartilage Frontal bone , parietal bone , temporal bone , the bones of face , part of occipital bone - formed in membrane CCD usually affects – bones formed from membrane

45. Clinical features (shoulder girdle) Partial or complete absence of clavicles or thinning of one or both clavicle. Unusual mobility of the shoulder and Ability to bring the shoulders together in front of the body until they meet in midline Chest is often found to be funnel shaped and sternum is depressed Diminishing in size, origin and insertion of sternocleidomastoid, subclavian, pactoralis major, deltoid and trapezius muscles are found

46. Clinical features(skull and head) Delayed or incomplete closure (ossification) of the space between the bones of the skull (fontanels) – tend to be large Frontal , partial and occipital bones are prominent – give the skull large globular shape with small face Premature closing of the coronal suture with interposition of wormian bone. Relative macrocephaly , depressed nasal bridge and defects may occur at the bregma Paranasal sinuses and mastoid air sinuses are underdeveloped and narrow

47. Other findings Short stature Scoliosis of the spine Wide pelvic bone Loose joints Shortened middle phalanges Hearing loss and/or frequent infections

48. Dental findings Maxilla is commonly micrognathous Mandibular prognathism High, narrow arched palate with median furrow A complete cleft of bony tissue of palate with soft parts intact has been reported Lacrimal and zygomatic bones are – underdeveloped

49. Prolonged retention of the primary teeth and Delayed appearance or unerupted permanent teeth. Delayed and arrest of physiological root resorption and bone resorption can be attributed as cause Unusually shaped and peg-like teeth Formation of supernumerary teeth can be found in all region , ectopic eruption of these teeth can be found. Formation of dentigerous cyst is common. 1 st and 2 nd molar erupts normally and 3 rd molar missing completely Enamel defects , curved roots are common All this leads to malocclusion and accentuates liability of caries , periodontal problems and hypertrophied gums.

50. Treatment There is no specific treatment for the bone problems. Early institution of preventive care problems Endocrinological investigation should done Administration of thyroid extract and vitamin therapy to stimulate eruption An otologist should check for hearing problems

51. Excellent oral prophylaxis should done Extraction of primary teeth is contraindicated and it should be restored Surgery may be performed to remove Supernumery teeth open the bony coverings surrounding the permanent teeth, with the goal of promoting their eruption. Orthodontic procedures: required to align the teeth . Construction of suitable prosthetic appliance Bilateral osteotomy should done to reduce mandibular prognathism

52. Marfan’s Syndrome Described by Parisian professor of pediatrics, Antoine Bernard Marfaan . 1896, presented a case of a 5 years old girl Gabrielle-Spider fingers, -Slender limbs. Six year later, Mery and Babonneix noted a spinal curvature and thoracic asymmetry. Others- Cardiovascular abnormalities.

53. Generalized systemic disorder of connective tissue characterized by Dislocation of ocular lenses Long-bone overgrowth Long slender digits Proximal aortic aneurysms Autosomal dominant disease Both sexes equally Incidence 1:10,000

54. Reviewed infrequently at 5, 10, 13 and 16 years

55. Etiology An abnormal fibrillin was identified in the skin and aorta of the affected patients An abnormal fibrillin was linked in chromosome 5. FBN1 is a major component of extracellular microfibrils . Abnormal fibrillin – stiffness.

56. Clinical manifestations Phenotypically the tissues are commonly affected are: Growth plates of the long-bone Eyes Aortic root Mitral apparatus Overgrowth of arms and legs Wrist sign or Walker- Mudrock Steinberg or a thumb sign

57. According to system affected 1. Skull Tall stature Arachnodactyly Funnel chest, pigeon chest Scoliosis Kyphosis Flat feet Contracture of finger Joint laxicity Degenerative arthritis

58. 2 . Ocular Octopia lentis Magalocornea Myopia Retinal detachment 3. Cardiovascular Mitral valve prolapse Mitral valve regurgitation Aortic root dialatation Aortic regurgitation ECG abnormalities

59. 4 . Pulmonary Pneumothorax 5. Skin and integument Strai atrophicae Inguinal hernia Dural ectasia 6. CNS Poor motor performance Attention deficit disorder Learning disability

60. CRANIOFACIAL MANIFESTATIONS: Long narrow skull High arched palate Severe periodontitis Tooth crowding Rettrognathia Micrognathia Malar flattening Downward slanting of palpebral fissures Local hypoplastic enamel defects

61. Cleft palate Bifid uvula Teeth – long and narrow Malocclusion Partial anodontia TMJ disorders Abnormal dentin formation Abnormal pulp shape and root deformity

62. Medical management Complete evaluation by a pediatric cardiologist and a geneticist. Include a systemic appraisal of the several non cardiovascular systems Cardiac evaluation include a detailed general physical evaluation and to detect signs of heart failure from mitral valve disease Mitral valve surgery is important Beta- adrenergic blockade – atenolol At each follow up – echocardiographic measurement of the aortic root diameter and shape.

63. Should undergo yearly assessment by ophthalmologist. Patient should be counselled not to engage in contact sports, competitive athletics, or isometric exercise.

64. Dental management Daily dental care Consult a cardiologist for antibiotics before dental procedures Consider if dental or orthodontic work is needed Important to balance treatment of dental issues against risks to the heart When an individual requires a lot of dental treatment- under sedation.

65. Craniofacial Dysostosis Crouzon syndrome is a genetic disorder characterized by the premature fusion of certain skull bones ( craniosynostosis )which prevents the skull from growing normally and affects the shape of the head and face.(Harold Chen,2007) In 1912 Crouzon first described a woman and her daughter with this disorder. Caused due to defect in FGFR2 gene (fibroblast growth factor receptor 2) in chromosome 10.

66. Global incidence : 1 in 25,000 live births (Acc to Johnston in Behrman (2004) Nelson Pediatrics, p. 1992-3) Detected in the newborn or infant period

67. Types: Brachycephaly Scaphocephaly Plagiocephaly trigonocephaly

68. Craniofacial manifestations Early synostosis of sutures mainly coronal suture Patients nose resembles Parrots beak Ocular proptosis Hypertelorism and exophthalmous May often be mentally retarded

69. Dental findings V-shaped maxillary dental arch Hypoplasia of maxilla with prognathic mandible (Class III Malocclusion) High arched palate Short hypotonic lips Crowding of the upper teeth

70. Treatment Mainly done for cosmetic purpose and for vision. Sometimes Craniectomy is done at an early age-to provide space for rapidly developing brain Frontoorbital Advancement to correct ocular defects Midface Advancement to correct maxillary hypoplasia Sagittal split osteotomy with mandibular setback to correct mandibular prognathism

71. Dental Management: Orthodontic evaluation – at an early age Might require extraction of some permanent teeth as well as expansion of maxilla.

72. Apert Syndrome Apert syndrome (AS) is a severe disorder, characterized by craniosynostosis and complex syndactyly of the hands and feet and midfacial hypoplasia (Newfoundland Department of Education,1992). In 1906, Eugène Apert , first described nine people with this disorder In 1995, A.O.M Wilkie proved that acrocephalosyndactyly is caused by a defect in a gene called fibroblast growth factor receptor 2, on chromosome 10 Occurs in approximately 1 per 160,000 to 1 per 200,000 live births( Acc to Kaplan, L C (2004).)

73. In India 1 in 1923 ( Acc to M.L.Kulkarni2004) Detected in newborn period males and females are affected equally. Clinical features Early closure of sutures between bones of the skull Acrobrachycephaly (tower skull) Ocular proptosis

74. Severe under-development of the mid-face Fusion or severe webbing of the 2nd, 3rd, and 4th fingers, often called " mitten hands" Webbing or fusion of the toes slow intellectual development Short height Hearing loss Frequent ear infections

75. Oral findings Trapezoid like mouth with protruded lips Delayed and/or ectopic eruption and shovel-shaped incisors. Supernumerary teeth Or bifid uvula Maxillary hypoplasia Class III Malocclusion Cleft lip Cleft palate

76. Treatment Craniectomy is performed during 1 st year of life to treat craniosynostosis Frontofacial advancement and midface advancement to correct proptosis and midface hypoplasia respectively. Combined orthodontic and orthognathic surgery can help to relieve some of the facial deformities, such as the flat or concave face. LeFort III, can be used to detach the midface from the rest of the skull to reposition it appropriately.

77. Corrective surgery is only undertaken if the child has a reasonable chance of living for some time as it is usually fatal within the first six months of life.

78. Autosomal r ecessive conditions

79. Cystic Fibrosis It is a chronic disabling disease associated with early demise. Caused by mutation of CFTR gene on long arm of chromosome 7. Gene is responsible for regulation of cellular chloride channels. Influence salt and water movement across cell.

80. Pathophysiology

81. Manifestations ENT: Chronic Sinusitis, Nasal Polyps Lungs : Cough and sputum, Airflow obstruction Recurrent infection GI: Pancreatic insufficiency (malnutrition) Pancreatitis ( PS), Meconium ileus , Biliary cirrhosis and portal hypertension Sex organs: Obstructive azoospermia Others: Salty tasting skin Poor growth and poor weight gain

82. Oral Manifestations Oral mucous glands are affected Salivary gland enlargement Thick ropy saliva Enamel defects Periodontal disease Dental caries Tooth discoloration

83. It can be detected by a positive history of chronic airway disease and can be confirmed using a sweat test. Treatment: Promote clearance of secretions Control of lung infection Provide adequate nutrition Prevent intestinal obstruction oral hygiene instruction for infection control

84. X-Linked conditions

85. Mutation in genes located on X-chromosome. Females are carrier and do not normally manifest the disorder. Males, on other hand only have one X chromosome which is inherited from mother, 50% chances of manifesting the disease. Example: Hemophilia X-linked hypohydrotic ectodermal dysplasia Fragile X-syndrome.

86. Hemophilia It is a group of hereditary genetic disorders. Impairs the body’s ability to control blood coagulation Occurs only in males while females being carrier. Types: Hemophilia A: Deficiency of clotting factor VIII. Hemophilia B: Deficiency of factor IX. Hemophilia C: Deficiency of factor XI.

87. Signs and symptoms: - Internal or external bleeding episodes Mild: 5-40% Moderate: 1-5% Severe: Less than 1% - Persistent bleeding - Hemorrhage into subcutaneous tissues, internal organs and joints. - Massive hematomas.

88. Prolonged clotting time and aPTT Children with mild to moderate hemophilia may not any signs or symptoms at birth First symptoms are large bruises and hematomas from frequent falls Hemophilia A can be mimicked by von Willebrand’s disease. Severe cases of vitamin K deficiency can present similar symptoms to hemophilia.

89. Management: - Intravenous injection of factor VIII concentrate Oral considerations: - 30% factor rise is essential for infiltration anesthesia in maxillary arch - For extractions, deep scaling or root planing , 50% factor rise is essential. - For surgical extractions, fractured jaw or facial bones, 100% rise may be necessary.

90. The problem of dental extractions is a difficult one Without proper premedication, even minor surgical procedure may result in death. Tooth extraction by means of rubber bands has been used successfully. Tranexamic acid mouthwash 10% for 7-10 days after extraction Soft diet for 7 days Fibrin glue as local hemostatic agent Splints can also be used.

91. Fragile X Syndrome It is secondary to an abnormality of a gene near the end of long arm of chromosome X. Males affected are moderately retarded and require a sheltered existence throughout life. Carrier females are mildly affected. Physical alteration are not reliable indicators, although prognathism , long face and ears are typical.

92. Physical characteristics: - Long narrow face - Prominent ears, jaw, chin - Excessive growth rate during early childhood years - May have intellectual disability -Autistic like behaviors -Strabismus and slanted eyes - Poor muscle tone and co-ordination - 15-20% of patients may have seizures.

93. It is important for the dentist to provide the parent with the information and tools required to assess and maintain good oral hygiene and healthy dietary practices for these children.

94. Ectodermal Dysplasia An X-linked recessive disorder Abnormal development of ectodermal derivatives such as nails, teeth, hair and sweat glands. Rare genetic disorder with incidence of 0.00005% Most frequently observed is the anhidrotic X-linked form.

95. Ectodermal Dysplasia Clinical features: Dry and rough skin and Heat intolerance Facial pigmentation Sparse hair Abnormal nails Typical face: frontal bossing, peri -orbital pigmentation, depressed nasal bridge, protuberant lips, low set ears and scanty scalp hair. Moderate built and poorly nourished.

96. Intra-oral manifestations: Aberrations in number and shape of teeth Malformed teeth – conical shape CI and LI. Premature caries Gingivitis Early tooth loss of both the dentitions Premature exfoliation Dry and sticky oral mucosa Knife edge alveolar ridges Partial anodontia/ hypodontia

97. Radiographic manifestations: Altered morphology of teeth Aplasia of alveolar bone Mandibular aplasia Decreased lower facial height

98. Management: Dry skin: emollients For decreased lacrimation: artificial tears For dry nasal mucosa: saline sprays Antibiotics for any infection occurs For dental malalignment: orthodontic treatment Surgery for oral and dental rehabilitation Prosthesis for missing teeth

99. Polygenic conditions

100. Cleft Lip And Cleft Palate Most common congenital malformation occurring in man and is of a polygenic condition. Results from multiple genes and gene-environmental interactions rather than a single gene defect. In polygenic conditions, the incidence is 1:800 with a recurrence rate of 4%. Combined cleft lip and palate: More common in males Isolated cleft palate: More common in females

101. Unilateral defect more common than bilateral defect In unilateral defects: left side is more common

102. Clinical features: Difficulty in speech, hearing and swallowing Supernumerary teeth or congenitally missing teeth Peg shaped teeth Thick curved hypoplastic incisors Delayed eruption of permanent teeth Isolated enamel defects Feeding difficulties

103. Clinical significance: - It is customary to operate the cleft before the patient is one month old. - Eating and drinking are difficult because of regurgitation of food and liquid through nose. - Speech problem is also serious

104. Treatment Requires an experienced team including otolaryngologist, speech pathologist, dentist and psychologist. Requires years of specialized care. At birth, predental treatment is provided which comprises feeding plate and presurgical orthopedics. Timing of first lip surgery – at 3 months of age. Pediatricians follow rule of ‘three 10s’ as a requirement for identifying the child’s status

105. Neural Tube Defects Multifactorial inheritance These conditions result from defective closure of the developing neural tube during the first month of embryonic life. A defect occurring at the upper end of the developing neural tube results in encephalocele. A defect occurring at the lower end leads to a spinal lesion such as lumbo-sacral myelocele.

106. Neural tube defects seldom affect the oral area directly but may cause changes indirectly because of a resulting hydrocephalus or seizure disorder that requires anticonvulsants. Repair of primary lesion is preformed early to protect CNS infections. Learning problems may be present in mild or more severe degrees depending on whether a CNS infection or hydrocephalus has been present. Leg bracing or wheelchair use is usual.

107. For dentist, subacute bacterial endocarditis prophylaxis may be important when a shunt tube or catheter is present, especially if the tip of the distal end of the shunt has been placed within the ventricle of heart.

108. Chromosomal syndromes

109. Down’s Syndrome A chromosomal condition characterized by physical malformations and some degree of mental retardation, concerned with a defect in the twenty-first chromosome(presence of three representative chromosomes in a cell instead of the usual pair)(Miller & Keane, 1972). Most common chromosomal disorder in humans. Also known as mongolism and trisomy 21 ( Acc to Schreiner1992 ) Dr LANGDON DOWN first described it in the clinical lecture report in London hospital in 1866 In 1959, Lejeune and Jacobs independently determined that Down syndrome is caused by trisomy 21 .

110. Incidence of Down Syndrome 1-in-800 overall births( global) – acc to Center for Disease Control 2006) In India 1 in 1139 live births( acc to M.P. Kava,2004) Incidence extrapolations of USA for Down Syndrome: 340,000 per year (Association for Children with Down Syndrome2003)

111. Pathogenesis In 90% of cases down’s syndrome occur due to nondisjunction which occurs during first and second meiotic division It occurs in offspring of mothers of all ages but the risk increases with the increase in maternal age

112. Types Trisomy 21( presence of extrachromosome ) Translocation type ( extra chromosome is not free but translocated on any other chromosome usually 13 or 15) Mosaicism ( some cells have 46 and the other cells have 47 chromosomes)

113. Common physical signs include : Decreased muscle tone at birth Excessive skin at the nape of the neck Flattened nose Separated sutures (joints between the bones of the skull) Single crease in the palm of the hand(Simian Crease)

114. Small ears Upward slanting eyes Wide, short hands with short fingers White spots on the colored part of the eye ( Brushfield spots) Slower Physical development than normal Widely spaced toes

115. Craniofacial features Brachycephaly due to failure of basal segments to elongate normally Bony hypoplasia of midface produces ocular hypotelorism Flattening of nasal bridge Relative mandibular prognathism The ears are small in size Maxillary sinuses are hypoplastic

116. Many different medical conditions are seen in babies born with Down syndrome, including Birth defects involving the heart such as an atrial septal defect or ventricular septal defect Eye problems such as cataracts Hearing problems Sleep apnea

117. Oral manifestations Macroglossia with protrusion of tongue Fissured tongue Retardation of growth of maxilla Commonly have high arched palate Enamel Hypoplasia & microdontia Delayed eruption and early shedding of deciduous dentition Defective or absent upper incisor

118. Tooth shape anomalies Bruxism Malocclusion Congenital absence of permanent teeth Prevalence and severity of periodontal diseases is much higher Caries susceptibility is low

119. Natural history Most children are happy ,affectionate and well behaved Affected child shows broad range of intellectual activity IQ ranges from 25-75 average being 40-45 ( American Association Of Mental Deficiency Classification) Adult height around 150 cms Average life expectancy 50-60 years Early death in 15- 20% with severe cardiac abnormalities Most people develop Alzheimer’s disease later in life

120. Management Medical management, home environment, education, and vocational training. There is no specific treatment for Down syndrome, special education and training is offered in most communities for children with delays in mental development. Speech therapy may help improve language skills. Physical therapy may be needed to teach movement skills .

121. Dental Management Abnormalities related to Down Syndrome that can affect dental treatment are congenital heart disease and behavioural problems due to retardation Provide oral care in an environment with few distractions . Use of fluoride should be enhanced to reduce caries Try to reduce unnecessary sights, sounds, or other stimuli that might make it difficult for your patient to cooperate. Most of patients with Down syndrome are friendly and co-operative Premedication may be given to allay apprehension

122. Systemic factors affecting dental care Complete medical history should be taken & reviewed Consult family, physician and caregivers to obtain proper medical history Almost 50% of these patients have cardiac abnormality so they require antibiotic prophylaxis before dental treatment These pts have compromised immune system which causes higher rate of infection and high incidence of periodontal disease Most of the pts have upper respiratory tract infection causing mouth breathing

123. Greater incidence of apthous ulcers, candida infections and ANUG which should be treated aggresively Importance of fluoride application should be stressed to prevent caries Use of lip balm should be done to ease the strain on lips Reduced muscle tone causes inefficient cleaning and natural cleaning of teeth Use of pillows should be done to stabilize the patients seizures are also common in these individuals can be controlled by using anticonvulsants

124. If seizure occur during treatment then instruments in the are to be removed from the mouth Pt should be turned on the side to reduce the risk of aspiration

125. Visual & hearing impairement affecting dental care The pt should be assisted throughout while moving in the clinic Tactile feedback like a warm handshake should be given to make them comfortable Dentist should talk while looking at him and should inform about each upcoming step Written instructions should be given in large print The hearing aids should be turned off

126. Sleep apnea The decreased airway size with lowered muscle tone predisposes the pt to sleep apnea Symptoms- snoring, restless sleep, unusual sleeping position refer the pt to the sleep disorders clinic Positive airway pressure and surgical correction is helpful Adenotonsillectomy proves helpful

127. Orofacial features affecting dental care Because of high arched palate and macroglossia there is difficulty in speech and mastication so speech pathologist should be consulted to teach correct tongue positioning and increase the tone of orofacial muscles Fissures of tongue may become food lodged leading to halitosis so regular cleaning of dorsal surface of tongue proves helpful Because of delayed eruption of teeth diet has to be modified In case of severe crowding after eruption of all permanent teeth selective extraction proves helpful

128. Spacing by microdontia - restoration or orthodontic correction Severe illness causes hypoplasia and hypocalcification -primary teeth should be preserved Space maintainers can be given Hypocalcified tooth should be observed in case of any early onset of decay Pit & fissure sealants, stainless steel crowns, fluoride application can be done Trauma or injury of oral cavity- tooth saving kit should be given

129. Periodontal disease- chlohexidine applied using spray bottle or tooth brush Regular maintainence of oral hygiene and professional cleaning is recommended

130. Turner’s Syndrome A chromosome disorder in females that is characterized by the absence of all or part of a second sex chromosome in some or all cells(Webster's New World Medical Dictionary2004) Described by Henry Turner in 1938 Missing X-chromosome(45,X) Global Incidence is 1 in 2500 Births( Sybert , V.P., McCauley, E. (2004). In India : 1 in 3000-(M. Patil,2006)

131. Clinical features Short stature Defective vision W ebbed neck Lower posterior hair line Auditory Defects Broad chest

132. Widely spaced nipples Streak ovaries, infertility Hypoplastic nails Pigmented nevi Oral Findings Small sized mandible High palate Narrow maxilla Multiple carious teeth

133. Treatment Estrogen replacement therapy from puberty onwards for of Secondary sexual characters and prevention of osteoporosis Growth hormone, approved by the U.S. Food and Drug Administration used for treatment of Turner syndrome will increases final height. Dental management of a patient with Turner syndrome . In case of multiple carious teeth, necessitated full mouth dental rehabilitation with the use of general anesthesia because of presence of cardiovascular abnormalities and long term antibiotic prophylaxis .

134. According to, National Health Institute of Child Health and Human Development , Orthodontic evaluation should be started at 7 yrs or more for treatment of malocclusion and other dental anomalies . Modifications that might be required to orthodontic treatment plans include (1) antibiotic prophylaxis, (2) occlusal adjustments to account for altered dental morphology, (3) altered treatment timing because of major differences in growth and differences between chronological and skeletal ages

135. Klinefelter’s Syndrome Klinefelter synd rome is a chromosomal disorder that affects only males having two X chromosomes in addition to Y chromosome . (Beers, Mark H., MD, and Robert Berkow,2004) This condition was first recognized by Dr. Harry Klinefelter in 1942 Global Incidence : 1 in 1000 male live births .(M.L. Hunter, MM Collard, T.Razavi & B. Hunter,2003) 1 in 800 males in India (Dada , A C Ammini , K Kucheria ,2005) Detected mostly during prepubertal period

136. Pathogenesis The extra X chromosome is usually acquired through an error of nondisjunction during gametogenesis, where a sperm or an egg caries an extra X chromosome in addition to normal single sex chromosome It may also result from an error in division during mitosis in the zygote

137. Clinical manifestations These patients are quiet, undemanding & little passive As toddlers they are a bit shy and reserved in nature and throughout the life they preserve the same temprament Although this they can make friends with other children but they tend to have only few friends at a time As children they learn to speak later in life These children show difficulty to put thoughts, express their emotions and ideas in words

138. Clinical features Tall height Abnormal body proportions (long legs, short trunk) Small, firm testicles Small penis Enlarged breasts( gynecomastia ) Scanty growth of hair

139. Dental findings Taurodontism Increased tooth size in permanent dentition increased mesiodistal width in primary incisors and molars. Shovel shaped incisors Maxillary and mandibular prognathism

140. Treatment Once a diagnosis is made, individuals should be referred to an endocrinologist who can monitor sexual development and initiate testosterone treatment at the appropriate stage of development. Testosterone from beginning of puberty, about age 11 to 12 years is beneficial for secondary sexual characters. once the therapy is started it should continue throughout life This therapy will also help to produce positive changes in mood and behaviour , muscle mass and bone integrity

141. Typical dose to maintain the normal serum testosterone level in adults is 200 mg every 2 weeks When started at puberty the dose is 50-100 mg initially with an increase of 50-100 mg every 2 to 4 weeks until adult dose is reached Surgical treatment is usually done to reduce gynecomastia and can be very well treated with plastic surgery

142. Dental management Maintain good oral hygiene to reduce gingival inflammation Endodontic management of a taurodontic symptomatic molars and premolar under L.A . Preformed SS crowns are recommended for treatment of taurodont molars because of poor oral hygiene and recurrent caries due to lack of patients cooperation and medication induced xerostomia

143. Conclusion As a pediatric dentist, we are the ones who might encounter the patient at an early age and hence, enough knowledge about the genetic abnormalities helps us to diagnose and treat easily.

144. References EMERY’S elements of medical genetics , 11 th edition, Robert F , Ian D young . GENES IN POPULATION-ELIOT B SPIESS(2 ND EDITION) Textbook Of Pedodontics 2003(1 st Edition): Shobha Tandon PRINCIPLES AND PRACTICE OF PEDODONTICS2006(1 st EDITION):ARATHI RAO BASIC HUMAN GENETICS,2 ND EDITION,2005:V KAPUR & RK SURI Human Genetics, Vol1 &2,2001,-Amita Sarkar SHAFER’S TEXTBOOK OF ORAL PATHOLOGY(5 TH EDITION)- SHAFER,HINE,LEVY

145. PEDIATRIC DENTISTRY:Infancy Through Adolescence,4 th EDITION-PINKHAM Mossey PA: The heritability of malocclusion. 2. The influence of genetics in malocclusion, Br J Orthod 26:,1999 Oral&Maxillofacial Pathology2005,2nd edition:Neville,Damm Allen,Bouquot Clinical Pedodontics(4 th edition)-Sidney B.Finn Ref:Genetic Rearrangement in Leukaemia and Lymphoma-I.M.Goldman&D.G.Hamden

146. Thank You