Syndromes (Dr. John Basile) Flashcards
Apert Syndrome (Acrocephalosyndactyly):
a) craniosynostosis-‐ premature closing of the cranial sutures
b) AD, sporadic mutations, increases with paternal age
c) acrobrachycephaly (tower skull); also have clover leaf skull
d) occular proptosis
e) hypertelorism
f) downward slanting lateral palpebral fissures
g) visual loss (chronic eye exposure, inc. intracranial pressure, compression of the optic nerve)
h) radiographs can show “beaten metal” appearance
i) hypoplastic midface-‐ lateral hard palate swelling due to accumulation of glycosaminoglycans (hyaluronic acid) which increases over time to produce a pseudocleft, respiratory distress, mouth breathing, and middle ear infections which can result in conductive hearing loss
j) limb defects unique to this syndrome-‐ syndactyly of 2nd, 3rd and 4th digits of hands and feet (synonychia). Synostosis of phlanges may be seen.
i) short stature
j) mental retardation
k) acne eruptions on the forearms
l) trapezoid shaped lips at rest
m) ¾ cleft of soft palate or bifid uvula
n) V-‐shaped arch and crowding of teeth
Ascher Syndrome:
a) double lip
b) blepharochalasis (sagging of upper eyelid at outer canthus of the eye due to edema)
c) non-‐toxic thyroid enlargement
Beckwith Wiedemann Syndrome:
a) p57 deletion
b) omphalocele (protrusion of part or all of the intestine through a defect in the abdominal wall at the umbilicus)
c) visceromegaly
d) gigantism
e) neonatal hypoglycemia
f) inc. risk of visceral tumor like Wilms, adrenal carcinoma and hepatoblastoma
g) nevus flammeus of the forehead and eyelids
h) linear indentations of the earlobes
i) maxillary hypoplasia
Brooke-‐Spiegler Syndrome:
a) familial turban tumor syndrome
b) 16q12-‐q13
Carney’s Triad:
a) extra-‐adrenal paraganglioma
b) gastric leiomyosarcoma
c) pulmonary chondroma
Cleidocranial Dysplasia (Cleidocranial Dysostosis):
a) short stature
b) broad base of the nose with depression of the nasal bridge
c) large head (frontal and parietal bossing)
d) hypoplastic midface (relative prognathism)
e) ocular hypertelorism
f) long neck with narrow drooping shoulders
g) hypoplastic or aplastic clavicles
h) supernumary teeth with distorted crowns and roots
i) delayed or failed eruption of permanent teeth
j) narrow high-‐arches palate
Cowden’s Syndrome (Multiple Hamartoma Syndrome):
a) malignancies, in addition to benign hamartomas, may
develop
b) cutaneous manifestations appear in the 2nd decade-‐ multiple small trichilemmomas (hair follicle hamartomas) of the facial skin, particularly around the nose and ears
c) acral keratosis (a warty growth on the dorsum of the hand) and palmoplantar keratosis
d) also see hemangiomas, xanthomas and lipomas
e) thyroid disease (goiter or thyroid adenoma)
f) fibrocystic disease of the breast, breast cancer at ages younger than normal (usually bi-‐lateral mastectomies are recommended before 30 years of age)
g) multiple benign hamartomatous polyps of the G.I. tract
h) benign and malignant tumors of the GU tract
i) multiple papules of the gingiva, dorsal tongue and buccal mucosa (fibroepithelial hyperplasia)
j) high arched palate
k) the presence of two out of three-‐ multiple facial trichilemmomas, multiple oral papules and acral keratosis-‐ is diagnostic (also, family history)
CREST Syndrome
(calcinosis cutis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia):
a) autoantibodies to centromere proteins
Crouzon Syndrome (Craniofacial Dysostosis):
a) craniosynostosis-‐ premature closing of the cranial sutures
b) AD, can arise as a new mutation
c) brachycephaly (short head)
d) scaphocephaly (boat shaped head)
e) trigonocephaly (triangular shaped head)
f) cloverleaf skull
g) ocular proptosis (shallow orbits)-‐ visual impairment
h) “beaten metal” pattern to radiographs
i) mid face hypoplasia (underdeveloped maxilla with crowded maxillary teeth and swollen palate leading to pseudocleft)
Cushing’s Disease:
hypercortisolism
Darier’s Disease:
AD, high penetrance, variable expressivity
b) 2nd decade-‐ numerous erythematosus pruritic papules on the skin of trunk and scalp which have extra keratin (can be associated with a foul odor due to bacteria). It’s worse in the summer.
c) pits and keratosis in palms and soles
d) longitudinal lines and ridges on nails, painful splits in nails
e) multiple normal colored to white, flat topped papules of the mucosa that can result in a “cobblestone” appearance (hard palate and alveolar mucosa mostly, but can affect buccal mucosa or tongue). Palatal lesions can resemble papillary hyperplasia or nicotine stomatitis
f) recurrent obstructive parotid swelling
Down’s Syndrome:
a) Trisomy 21
b) enlarged tongue with papillary, fissured surface
Dyskeratosis Congenita:
) X-‐linked, becomes evident in the first 10 years of life
b) reticular skin hyperpigmentation (upper chest and neck)
c) dysplastic nail changes
d) tongue and buccal mucosa form bullae, which can lead to erosions and eventually pre-‐malignant leukoplakias (one third change to SCC in 10 to 30 years)
e) rapidly progressive periodontal disease
f) thrombocytopenia, aplastic anemia in 45% of patients)
g) mild to moderate mental retardation
h) life span of only ~32 yrs.
Eagle Syndrome (Stylohyoid Syndrome; Carotid Artery Syndrome)
a) mineralization of the stylohyoid ligament
b) facial pain when swallowing, turning head or opening mouth
c) dysphagia, dysphonic, otalgia
d) headache, dizziness and transient syncope
e) symptoms usually occur following tonsillectomy
Ectodermal Dysplasia:
a) X-‐linked; women can show partial expression (Lyon effect)
b) decreased sweat glands and hair follicle in the skin
c) fine, sparse blond hair
d) decreased density of eyebrow and lash hairs
e) wrinkling and hyperpigmentation of perioccular skin
f) mid-‐face hypoplasia
g) varying degrees of xerostomia
h) dystrophic, brittle nails
i) oligo or hypodontia
j) abnormal crown shapes to the teeth (tapered or conical, pointed incisors and a decreased diameter to molar crowns)
Ehler-‐Danlo’s Syndrome:
a) abnormal collagen production
b) hypermotility of joints, easy bruising and skin elasticity
c) Type I (severe) and II (mild) are AD; “papyraceous scarring”
d) Type III-‐ joint hypermobility but no scarring
e) Type IV-‐ ecchymotic type, showing bruising to everyday trauma and formation of aortic aneurysm, with a decrease in life expectancy
f) “Gorlin Sign”-‐ touching the tip of the nose with the tongue
g) subluxation of the TMJ
h) no correlation with changes in tooth morphology
i) pulp stones (like in dentin dysplasia, type II)
Type VIII - severe periodontal disease
Ellis-‐van Creveld syndrome (chondroectodermal dysplasia)
a) Fusion of the upper or lower lip to the gingiva
b) Absence of mucobucccal fold and fibrous bands
b) Median cleft of upper lip
c) Natal teeth
- chondroectodermal dysplasia
- autosomal recessive
- mutation in EVC and EVC2
- **Median cleft lip/palate **
- Short limbs dwarfism
- Genu valgum - knees to be touching while the ankles remain apart
- Postaxial polydactyly with a complete extra metacarpal,
- Ectodermal dysplasia with hypoplastic nails and teeth,
- Structural heart disease
- enamel hypoplasia, hypodontia, conical teeth, diastema, multiple labial gingival frenulae, labiogingival adherence, submucosal clefts, taurodontism
Gardner Syndrome:
a) AD, a form of familial colorectal polyposis
b) multiple adenomatous polyps of the colon and rectum
c) multiple osteomas (of facial bones)
d) cutaneous epidermoid cysts
e) fibromas
f) odontomas, supernumary teeth, impacted teeth
Goldenhar (Oculoauriculovertebral) Syndrome:
a) congenital condylar hypoplasia
b) macrostomia
c) malformed pinnae
d) looks like hemifacial atrophy
Goltz-‐Gorlin Syndrome (Focal Dermal Hypoplasia Syndrome):
a) perioral papillomata
b) coloboma of iris
c) syndactyly
d) linear skin lesions
e) hypodontia, dysplastic enamel
f) osteopathia striae
g) angiomata
Gorlin Syndrome (Nevoid Basal Cell Carcinoma Syndrome):
a) AD
b) benign adnexal tumors of the skin
c) multiple BCC of the skin
d) multiple jaw OKC
e) rib anomalies
f) vertebral anomalies
g) intracranial calcifications
h) frontal and tempero-‐parietal bossing
i) hypertelorism
j) mild mandibular prognathism
k) palmar and plantar pits (with BCC at the base)
l) shortened metacarpals
m) ovarian fibromas, uterine fibroids
o) medulloblastomas
p) mental retardation
q) cardiac anomalies (valve myxoma)
Heerfordt’s Syndrome (Uveoparotid fever):
a) parotid enlargement
b) anterior uveitis
c) facial paralysis
d) fever
e) acute sarcoidosis
Hereditary Benign Intraepithelial Dysplasia (Witkop-‐van Sallmann Syndrome):
a) AD, tri-‐racial natives of North Carolina
b) appears during childhood
c) oral and conjunctival mucosa-‐ in the mouth, it looks like white sponge nevus. In the eye there can be thick, gelatinous plaques of the conjunctiva
Hereditary Hemorrhagic Telangectasia (Osler-‐Weber-‐Rendu Syndrome):
a) AD
b) numerous vascular hamaromas of skin (hands and feet especially) and mucosa (lips, tongue, buccal mucosa) that blanche upon pressure
c) AV fistulas, sometimes in the brain (brain abscesses)
d) epistaxis
e) iron deficiency anemia (due to bleeding?)
f) consider CREST syndrome in the differential (anti-‐centromere antibodies are present in CREST, not HHT)
Hemifacial Microsomia:
congenital condylar hypoplasia
Horton’s Syndrome:
cluster headache
Hutchinson’s Triad:
a) enamel hypoplasia (Hutchinson’s incisor, mulberry molar)
b) VIII nerve deafness
c) interstitial keratitis
Incontinentia Pigmenti (Bloch-‐Sulzberger Syndrome):
a) X-‐lined, dominant
b) 4 stages to the clinical features:
1) Vesicular Stage-‐ vesiculobullous lesions (intra-‐epithelial clefts filled with eosinophils) appear on the skin of the trunk and limbs that resolve in 4 months
2) Verrucous Stage-‐ hyperkeratotic, acanthotic and papillomatous plaques develop on limbs that resolve by 6 mos. of age
3) Hyperpigmentation Stage-‐ macular brown skin lesions appear in a swirling pattern. Histologically, they appear as numerous melanin containing macrophages in the sub-‐epithelial connective tissue (melanin incontinence)
4) Atrophy and Depigmentation Stage-‐ atrophy and depigmentation of the skin occurs
c) CNS abnormalities (mental retardation, seizures)
d) occular problems (strabismus, cataracts and optic atrophy)
e) oligodontia/ hypodontia, delayed eruption and hypoplasia of teeth. Small, cone shaped teeth
Johanson-‐Blizzard Syndrome:
a) pulmonary insufficiency
b) hearing loss
c) imperforate anus
d) alar hypoplasia, beak nose
e) microdontia
f) skin defects over fontanelles
Li-‐Fraumeni syndrome:
a) p53 germline mutations
Löfgren’s Syndrome:
a) erythema nodosum
b) bilateral hilar lymphadenopathy
c) arthralgia
d) acute sarcoidosis
Maffucci’s Syndrome:
a) head and neck chondromas
b) spindle cell hemangioendothelioma
(both of these can undergo malignant transformation)
Mandibulofacial Dysostosis (Treacher-‐Collins Syndrome; Franceschetti-‐Zwahlen-‐Klein Syndrome):
a) defects in structures from 1st and 2nd branchial arches
d) AD, variable expressivity, increased with paternal age
e) narrow trachea, larynx and mandibular hypoplasia and condylar hypoplasia along with improper tongue position can lead to respiratory difficulties
f) characteristic facies:
1) hypoplastic zygoma (narrow face, depressed cheeks, downward sloping palpebral fissures, coloboma on the outer portion of the lower eyelid with no eyelashes medial to the coloboma)
2) deformed pinnae (extra ear tags)
3) ossicle defects, absence of external auditory canal leading to conductive hearing loss.
4) underdeveloped mandible with retruded chin, condylar hypoplasia and coronoid processes with antegonial notching (appears as a downturned mouth).
5) can see lateral facial cleft leading to macrostomia
g) cleft palate in 1/3 of cases
h) hypoplastic or missing parotid
Marfan syndrome:
a) Genetic disorder of the connective tissue.
b) Patients unusually tall, with long limbs and long, thin fingers
c) FBN1 gene, which encodes the connective protein fibrillin-‐1
d) Most serious complications heart valves and aorta defects
McCune-‐ Albright Syndrome:
a) Polyostotic fibrous dysplasia
b) café-‐au-‐lait spots (coast of Maine)
c) endocrine dysfunction (sexual precocity, esp. in females)
Melkersson-‐Rosenthal Syndrome
a) fissured tongue
b) lip granulomas (Orofacial granulomatosis-‐ this alone, in the lips, is called cheilitis granulomatosa of Miescher)
c) lymphangioma-‐like vesicles
d) facial paralysis (VII)
Mohr Syndrome
Oral-facial-digital syndrome type II
- autosomal recessive
- median cleft lip, poly lobed tongue, absence of medial incisors, and polydactyly of hands and feet
- talon cusp
Muir-‐Torre Syndrome:
a) sebaceous neoplasms
b) keratoacanthoma
c) GI carcinomas
Multiple Endocrine Neoplasia Syndrome, Type III (MEN IIb; Multiple Mucosal Neuroma Syndrome):
a) pheochromocytoma
b) medullary (C-‐cell) thyroid carcinoma
c) mucosal neuromas (bilateral commisures)
d) marfanoid body
Neurofibromatosis 1
≥ 2 of the following:
1) ≥ 6 café-‐au-‐lait spots
2) ≥ 2 NFs or 1 plexiform NF
3) axillary or inguinal freckles
4) optic gliomas
5) ≥ 2 Lisch nodules (iris hamartomas)
6) osseous lesions (sphenoid dysplasia or long bone cortical thinning +/-‐ pseudoarthrosis)
7) 1st degree relative with neurofibromatosis
Oro-‐Facial-‐Digital Syndrome
a) Digital malformations (brachydactyly, syndactyly)
b) Median cleft of upper lip
c) Extra teeth
d) Bifid tongue
e) Multiple hyperplastic frenula in upper/lower labial folds
Oromandibular-‐Limb Hypogenesis Syndrome:
a) microglossia
b) limb anomalies (hypodactylia-‐ missing digits; hypomelia-‐ hypoplasia of part or all of a limb)
c) CP
d) intraoral bands
e) situs inversus
f) hypoplasia of mandible w/ some missing lower incisors
Pachyonychia Congenita (Jadassohn-‐Lewandowsky Syndrome):
a) nail changes at birth-‐ nail lifts up due to accumulation of keratinaceous debris under the nail bed, giving the nail a pinched, tubular look. It can lead to nail loss
b) hyperkeratosis of palmar and plantar skin
c) punctate papules of the skin due to accumulation of keratin around hair follicles
d) painful blistering of the feet when walking in warm weather
e) thickened white plaques of the lateral margins, mainly on dorsal surface of the tongue
d) neonatal teeth
e) hoarseness and dyspnea (laryngeal mucosal involvement)
- Mutations in genes encode for keratin 6a, 6b, 16 or 17
- Oral lesions - keratin 6a (KRT6A)
- Neonatal teeth- keratin 17
Papillon-‐Lefevre Syndrome (Meleda’s Disease in the absence of oral symptoms):
a) AR
b) impaired T and B lymphocyte reactivity (chemotaxis defect and impaired ability to kill intracellular organisms)
c) palmar-‐plantar keratosis
d) occasionally diffuse follicular hyperkeratosis and keratosis
e) more prone to infections
f) oral manifestations:
1) advanced periodontitis (teeth “floating in air”)
2) pd destruction case by actinomyces (???)
Parry-‐Romberg Syndrome (Progressive Hemifacial Atrophy):
- atrophy on one side of the face
- en coup de sabre
Peutz-‐Jeghers Syndrome:
a) AD
b) freckles of hands, perioral skin, oral mucosa, nose, genitals and anus. These do not wax or wan in light exposure
c) intestinal polyposis (mostly jejunum and ileum)
d) intestinal obstruction due to intussusception (“telescoping” a proximal segment of bowel into a distal segment),
e) G.I. adenocarcinomas in 2 to 3% of patients. Generally the polyps are NOT pre-‐malignant
f) increased frequency of breast and ovarian tumors
Pierre-‐Robin Sequence (anomalad):
a) cleft palate
b) mandibular micrognathia
c) glossoptosis (airway obstruction due to lower, posterior displacement of the tongue)
Popliteal Pterygium Syndrome:
a) popliteal webbing (pterygia)
b) CL +/-‐ CP, paramedian lip pits (also seen in van der Woude)
c) genital abnormalities
d) congenital bands connecting upper and lower jaws (syngnathia)
Ramsay-‐Hunt Syndrome:
Reactivation of VZV in geniculate ganglion
a) Lesions of the external auditory canal
b) Involvement of the ipsilateral facial and auditory nerves.
c) Facial paralysis, hearing deficits and vertigo
VZV detected in 30%
Reye’s syndrome :
a) Rash, vomiting, and liver damage
b) Assoc w/ aspirin consumption by children with viral illness
Rubinstein-‐Taybi Syndrome:
1) Talon cusps
Sturge-‐Webber Syndrome
a) a non-‐hereditary, developmental condition
b) Port wine stain or nevus flammeus) along distribution of trigeminal nerve (if it’s along the ophthalmic branch, the pts have an inc. chance of suffering from the full condition)
c) leptomeningial angiomas associated with convulsions
d) gyriform “tram line” calcifications of the affected side
e) glaucoma, vascular malformations of eyes
GNAQ
Tricho-‐Dento-‐Osseous Syndrome
a) enamel hypoplasia and hypomaturation (AI)
b) osteosclerosis
c) brittle nails
d) kinky hair
Tuberous Sclerosis
a) AD
b) mental retardation
c) “tuberous” CNS hamartomas seen at autopsy
d) seizure disorders
e) angiofibromas of the skin-‐ multiple white smooth surfaced papules in nasolabial fold (facial angiofibromas, a.k.a. adenoma sebaceum) and ungual fibromas of the nail beds
f) Shagreen patches-‐ CT hamartomas of the trunk
g) Ash leaf spots-‐ ovoid areas of hyperpigmentation
h) cardiac rhabdomyoma
i) angiomyolipoma of the kidney
j) developmental pitting of enamel in facial anterior teeth
k) fibrous papules on mouth (esp gingival)
Urbach-‐Wiethe Syndrome (Lipid Proteinosis):
a) AR
b) deposition of waxy material in dermis and submucosal CT
c) affects the vocal cords at infancy
d) neck, palms, axillae, elbows, scrotum, knees, and digital skin
e) intracranial calcifications
f) loss of papillae of tongue (smooth tongue), which becomes bound to the floor of the mouth. Can affect labial mucosa and buccal mucosa as well.
