Study Notes for Clinical Syndromes Resulting From Chromosomal Abnormalities
Clinical Syndromes Resulting From Gross Chromosomal Abnormalities
Trisomy 21 (Down Syndrome)
Cause: One extra chromosome no. 21 due to nondisjunction.
Location: In utero.
Clinical/Radiographic Appearance: Characterized by systemic, multiple organ involvement.
Features include slanted eyes, gingivoperiodontitis, fissured tongue, macroglossia, dental anomalies like hypodontia, premature loss of teeth, and malposed teeth.
Treatment:
Root planing and scaling.
Frequent recare necessary.
Other Facts:
Most common of the trisomies, linked to late maternal age during conception.
Patients often have a reduced life expectancy; heart abnormalities are present in over 30% of cases.
Intelligence levels vary from near normal to markedly low, with gingival and periodontal diseases reported in 90% of patients.
Trisomy 13
Cause: One extra chromosome no. 13 due to nondisjunction.
Location: In utero.
Clinical/Radiographic Appearance:
Manifestations include bilateral cleft lip and palate, microphthalmia (small eyes) or anophthalmia (absence of eyes), and superficial hemangioma of the forehead or nape.
Patients may also experience impaired growth, severe mental handicap, polydactyly (extra digits on hands and feet), clenching of fists with the thumb under fingers, rocker-bottom feet, heart malformations, and various anomalies of external genitalia.
Treatment: None.
Other Facts:
Approximately 70% of live-born infants die within the first 7 months of life.
Turner Syndrome
Cause: Missing one X chromosome due to nondisjunction.
Location: In utero (women).
Clinical/Radiographic Appearance:
Features include short stature, webbing of the neck, edema of hands and feet, low hairline at the nape, broad chest with wide-spaced nipples, abnormal aorta, sparse body hair, and infantile external genitals.
Smears from the oral mucosa lack Barr bodies.
Treatment: None.
Klinefelter Syndrome
Cause: Presence of one or more extra X chromosomes due to nondisjunction of the X chromosome.
Location: In utero (men).
Clinical/Radiographic Appearance:
Tall stature, gynecomastia, hypoplastic maxilla, presence of one Barr body in buccal smear.
Treatment: None.
Other Facts: Affected individuals maintain a male phenotype; condition usually diagnosed post-puberty, and infertility is a common concern.
Cri du chat
Cause: Deletion of part of chromosome 5.
Location: From birth.
Clinical/Radiographic Appearance:
Characterized by a cat-like cry, severe mental disabilities, and micrognathia of the lower jaw.
Treatment: None.
Inherited Disorders Affecting the Gingiva and Periodontium
Cyclic Neutropenia
Cause: Autosomal Dominant.
Location: In utero; affects oral mucosa and periodontium.
Clinical/Radiographic Appearance: Characterized by a cyclic decrease in circulating neutrophils (neutropenia).
Leads to severe ulcerative gingivitis, periodontitis, painful ulcers, and bleeding.
Cycles usually occur every 21 to 27 days; episodes last 2-3 days, with the worst oral findings at the low point of neutrophil count.
Systemic symptoms include fever, malaise, and sore throat.
Evidence of alveolar bone loss and pocket formation.
Treatment:
Root planing, scaling, initiate dental treatment when neutrophil count normal.
Periodic treatment with granulocyte colony-stimulating factor (G-CSF) to reduce symptoms and improve clinical outcome.
Antibiotics for secondary infections; medical clearance before dental procedures.
Papillon-Lefevre Syndrome
Cause: Autosomal Recessive.
Location: In utero; affects gingiva, periodontal ligament, palms, and soles.
Clinical/Radiographic Appearance:
Characterized by significant periodontal tissue destruction and resulting in precocious tooth loss.
Palmar and plantar hyperkeratosis noted on palms and soles, teeth appear to float in tissues on radiography.
Both primary and permanent teeth are lost in the same order they erupted; all permanent teeth lost before age 14.
Peripheral blood neutrophil counts are consistently depressed, leading to severe periodontal disease.
Treatment:
Root planing, scaling, tooth fixation, topical retinoids for skin lesions.
No successful interventions to prevent periodontal destruction so far.
Ehlers-Danlos Syndrome
Cause: Autosomal Dominant disorder affecting collagen synthesis.
Location: In utero; affects skin, mucosa, joints.
Clinical/Radiographic Appearance:
Group of 13 rare connective tissue disorders caused by defects in collagen structure/processing.
Symptoms include bruising and bleeding, skin hyperelasticity, temporomandibular joint disorders (TMD), and Gorlin sign (ability to touch the nose with the tongue).
Loose, weak joints may be observed, potential for alveolar bone loss.
Treatment: Variable based on degree of oral manifestations.
Gingival Fibromatosis
Cause: Autosomal Dominant.
Location: In utero; affects gingiva, hair, central nervous system.
Clinical/Radiographic Appearance:
Marked gingival enlargement developing early in life, leading to complete coverage of teeth within a few years.
Characterized by firm tissue, gingival hyperplasia, abundant body hair, epilepsy, severe intellectual disability.
Gingival tissue color is paler due to marked collagenization of the fibrous connective tissue, protruding lips due to overgrowth.
Treatment:
Maintenance of oral hygiene; surgical remodeling of gingiva.
Inherited Disorders Affecting the Jawbones and Facies
Cherubism
Cause: Autosomal Dominant.
Location: Affects maxilla and mandible, often bilaterally with the mandible being the most common site.
Clinical/Radiographic Appearance:
The first clinical sign is progressive bilateral facial swelling, usually noted between ages 1.5-4 years.
Maxillary involvement may displace the eyes, leading to the appearance often described as 'eyes turned to heaven.' Ocular hypertelorism is always present.
Radiographs show multiple bilateral radiolucent areas described as “soap bubbles” mostly affecting the mandibular ramus and maxilla but not the condyle; these areas are found occupied by fibrous connective tissue with multinucleated giant cells.
Treatment:
Lesions may regress post-puberty; reconstructive surgery may be necessary after growth ceases.
Cleidocranial Dysplasia
Cause: Autosomal Dominant.
Location: Affects teeth, clavicles, and skull.
Clinical/Radiographic Appearance:
The cranium develops a mushroom shape due to open fontanelles; hypoplasia of the clavicles occurs.
Supernumerary teeth are common; affected individuals may approximate shoulders to midline due to clavicular abnormalities.
Radiographic findings include multiple impacted teeth and an underdeveloped premaxilla, absent cellular cementum.
Treatment:
Extractions, orthodontic treatments as needed.
Gardner Syndrome
Cause: Autosomal Dominant.
Location: Affects the polyposis primarily in the colon and rectum, generally developing before puberty, with involvement in the maxilla, mandible, and skull (especially frontal bones).
Clinical/Radiographic Appearance:
Characteristic benign bone growths (osteomas) that can induce facial asymmetry and obliterate sinuses when expanded, along with potential multiple odontomas (benign tumors of tooth development).
The most serious aspect is the presence of multiple adenomatous colorectal polyps that can become malignant after age 30, leading to adenocarcinoma development.
Supernumerary teeth may also be present.
Treatment:
Surgical intervention may be required for polyps and/or carcinoma, odontomas, and osteomas.
Mandibulofacial Dysostosis (Treacher Collins Syndrome)
Cause: Autosomal Dominant.
Location: Affects mandible, teeth, and ears.
Clinical/Radiographic Appearance:
Characterized by a dysmorphic facial appearance, notably downward sloping palpebral fissures, hypoplastic nose, malar bones, misplaced ears, and a receding chin from a hypoplastic mandible.
Consistent hearing difficulties accompany the syndrome; dental manifestations include malposed teeth and malocclusion, usually with an open bite.
Notable features include a high vaulted palate with a 30% prevalence of clefting and acute mandibular angles, and a diminished size of the condyle.
Treatment:
Plastic surgery, orthodontic care, and maintenance of oral health.
Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome)
Cause: Autosomal Dominant.
Location: Affects mandibular and maxillary regions, skin, ribs, and face.
Clinical/Radiographic Appearance:
Characterized by palmar and plantar pitting (depressions), typically associated with basal cell carcinomas (skin cancers) and multiple odontogenic keratocysts of the jaws.
Various neoplasms have been observed with this syndrome, including medulloblastomas (brain tumors) and calcified falx cerebri, which indicates the calcification of a brain separation tissue. Hypertelorism and frontal bossing are also seen.
Treatment:
Surgical excision of cysts and basal cell carcinomas as needed.
Osteogenesis Imperfecta
Cause: Genetic mutations affecting the production of type I collagen.
Location: Affects skeleton and teeth.
Clinical/Radiographic Appearance:
Presented with multiple skeletal deformities classified into four types (I, II, III, IV).
The prime clinical feature involves frequent spontaneous bone fractures. Severe cases may lead to all bones being affected; milder cases display only blue sclerae (a blue appearance of the whites of the eyes).
Dental manifestations present as a dentinogenesis imperfecta-like condition, often with underdeveloped tooth structures and compromised enamel support.
Treatment:
Symptomatic management and dental restorations.
Mandibular Tori
Cause: Autosomal dominant inheritance with variable expressivity and marked penetrance.
Location: Present on the lingual aspect of the mandibular premolar region.
Clinical/Radiographic Appearance:
Characterized as benign, bony growths; sizes can vary and occasionally may be multilobulated.
Typically asymptomatic; radiographic findings usually reveal a radiopacity in the mandibular premolar region if present.
Treatment:
Typically none, but surgical removal may be warranted if denture fitting is necessary.
Torus Palatinus
Cause: Autosomal dominant inheritance with variable expressivity and nearly 100% penetrance.
Location: Midline of the hard palate; becomes evident around puberty.
Clinical/Radiographic Appearance:
Bony overgrowth, which can range from negligible to large masses occupying significant areas of the hard palate.
Some torus growths may be multilobulated; generally asymptomatic, but the thin surface mucosa can be prone to trauma.
Treatment:
None typically needed, although removal may be required for denture applications.
Maxillary Exostoses
Cause: Autosomal dominant inheritance pattern.
Location: Buccal aspect of the maxillary alveolar ridge, primarily in molar and premolar areas.
Clinical/Radiographic Appearance:
Manifest as symptomless bony projections unless trauma occurs.
Can be singular, multiple, unilateral, or bilateral in distribution.
Treatment:
Usually none; surgical removal can be performed but may recur.
Inherited Disorders Affecting the Oral Mucosa
Isolated Cleft Palate and Cleft Lip With or Without Cleft Palate
Epidemiology: Occurs in approximately 1 in 800 births, contrasting the rare syndromes previously discussed.
Pathophysiology: Primarily multifactorial in origin.
Associations: Several inherited syndromes may include cleft lip and palate or isolated cleft palate as features.
Hereditary Hemorrhagic Telangiectasia
Cause: Autosomal Dominant.
Location: Affects mucous membranes and skin, notably at the tip of the tongue.
Clinical/Radiographic Appearance:
Manifested by multiple capillary dilations of skin and mucous membranes, especially noted as pinpoint and spider-like telangiectases on facial skin.
Similar lesions cause frequent and potentially serious nosebleeds (epistaxis) lasting several days.
Oral telangiectases, especially present on the anterior tongue and lips, lead to oral hemorrhages.
Treatment: Caution is needed during scaling due to the significant bleeding tendency.
Neurofibromatosis I (von Recklinghausen Disease)
Cause: Autosomal Dominant, originating from neural crest tissues.
Location: Affects skin, eyes, and oral mucosa, particularly the tongue.
Clinical/Radiographic Appearance:
Comprises multiple neurofibromas manifesting as papules and growths of varying sizes on facial skin, predominantly around the eyelids.
Neurofibromas can also appear on the tongue and other oral areas, with some potentially undergoing malignant transformation.
Café au lait pigmentation noted on the skin typically precedes development of neurofibromas; radiolucencies can occur in the mandible.
Treatment: Surgical removal of neurofibromas.
Peutz-Jeghers Syndrome (Hereditary Intestinal Polyposis Syndrome)
Cause: Autosomal Dominant.
Location: Involves skin, eyes, nose, oral mucosa, and small intestine.
Clinical/Radiographic Appearance:
Characterized by multiple melanotic macular pigmentations on the skin and mucosa, associated with gastrointestinal polyposis.
The intestinal polyps are mostly hamartomas, occurring primarily in the small intestine, rarely transforming malignantly, unlike Gardner syndrome where polyps are at high risk.
Treatment: Removal of intestinal polyps if necessary.
White Sponge Nevus
Cause: Autosomal Dominant, presents from birth or develops at puberty.
Location: Buccal and labial mucosa.
Clinical/Radiographic Appearance:
Characterized by a white, corrugated, soft, and folded oral mucosa due to thick keratin layers that can desquamate, leaving raw surfaces.
Treatment: None; focus on maintenance of oral hygiene.
Amelogenesis Imperfecta
Overview: A group of inherited conditions affecting tooth enamel without systemic defects.
Types of Amelogenesis Imperfecta:
Type I: Hypoplastic amelogenesis imperfecta.
Cause: Autosomal Dominant.
Location: Visible upon tooth eruption, affecting all primary and permanent teeth.
Clinical/Radiographic Appearance: Random pinpoint pits on labial and lingual surfaces; enamel fails to reach normal thickness due to ameloblast failures. Enamel remains calcified.
Treatment: Esthetic dentistry, operative procedures.
Type II: Hypocalcified amelogenesis imperfecta.
Cause: Autosomal Dominant or Recessive.
Location: Affects all primary and permanent teeth at eruption.
Clinical/Radiographic Appearance: Enamel of normal thickness but poorly calcified, presenting a yellow-to-orange hue, soft structure that is rapidly lost exposing dentin. Radiographically shows a moth-eaten appearance.
Treatment: Esthetic dentistry, operative procedures, laminates.
Type III: Hypomaturation amelogenesis imperfecta.
Cause: Inheritance may be Autosomal Dominant, Recessive, or X-linked.
Location: In all primary and permanent teeth at eruption.
Clinical/Radiographic Appearance: Mottled enamel appearance yet of normal thickness; softer than normal and prone to chipping. Radiographically, the enamel has the same radiolucency as dentin and can be easily penetrated by a dental explorer.
Treatment: Focus on esthetic dentistry and operative procedures, laminates.
Type IV: Hypoplastic-hypomaturation amelogenesis imperfecta.
Characteristics: Associated with taurodontic teeth, with thin yellow to brown pitted enamel. Radiographic density of enamel matches dentin, single-rooted teeth show enlarged pulp chambers.
Dentinogenesis Imperfecta
Cause: Autosomal Dominant.
Location: Affects all primary and permanent teeth.
Clinical/Radiographic Appearance:
Characterized by bulbous crowns ranging from opalescent brown to blue, short roots, and absence of pulp chambers.
Abnormal dentin structure results in soft dentin that may chip enamel leading to attrition, potentially reducing teeth to alveolar processes due to severe deterioration.
Treatment: Esthetic dentistry, crowns, operative procedures.
Hypohidrotic Ectodermal Dysplasia
Cause: X-linked recessive or Autosomal Recessive.
Location: Affects skin, sweat glands, hair, and both dentitions.
Clinical/Radiographic Appearance:
The syndrome manifests with hypodontia (partial anodontia), hypotrichosis (decrease in hair), and hypohidrosis (reduced sweat secretion) often leading to hyperthermia in patients after exposure to heat or exercise.
Characteristic facial features include frontal bossing, depressed nasal bridge, protuberant lips, and lack of scalp hair.
Treatment: Options include dental implants and/or prosthetic appliances.
Hypophosphatemic Vitamin D–Resistant Rickets
Cause: X-linked dominant.
Location: Can affect bones and teeth.
Clinical/Radiographic Appearance:
Notable for periapical radiolucencies, significantly large pulp chambers, and abnormal dentin resulting in fissures. Patients exhibit low phosphate absorption leading to rickets in childhood or osteomalacia in adults, with short stature and leg bowing frequently observed.
Treatment: Endodontics and regular dental hygiene management.
Peg Laterals
Cause: The inheritance pattern for pegged or absent maxillary lateral incisors appears to be autosomal dominant with variable expressivity.
Location: Can affect both primary and secondary dentitions, commonly observed in maxillary lateral incisors.
Clinical/Radiographic Appearance:
Affected incisors may be small or peg-shaped or congenitally absent, either unilateral or bilateral.
Treatment: Cosmetic restorations as needed.
Taurodontism
Cause: Can be Autosomal Dominant or Recessive.
Location: Primarily affects molars.
Clinical/Radiographic Appearance:
Characterized by enlarged pulp chambers with apically displaced root furcation, frequent associations noted with Klinefelter syndrome and other syndromes.
Treatment: Typically none required, unless symptomatic.