Clinical Genetics Final

TGFa

growth factor important for epithelial development and palatine arch development

TGFb

growth factor important for palatal shelf elevation and fusion

TBX22

transcription factor important for palatogenesis and tongue development

IRF6

transcription factor and immune response

MSX1

transcription factor

RARA

nutritional metabolism

SHH

palatal mesenchymal cell proliferation and BMP+FGF signaling
tooth development
organogenesis
mutation: holoprosencephaly

SADD TV - environmental factors contributing to CL/CP

smoke
alcohol
diet
drugs
teratogens
viral

Malformations

poor formation of tissues

Deformations

abnormal biomechanical forces on normal tissues

Disruptions

destructive forces leading to tissue breakdown

Fetal Alcohol Syndrome

CL/CP

Potter Sequence

low oligohydroaminos (amniotic fluid)
CL/CP

Marfan Syndrome

CT disorder: eyes, joints, bones, blood vessels
large blood vessels and heart - life threatening
CP
fibrillin 1 affecting tgf beta signaling

Loeys-Dietz syndrome

bifid uvula, tortuosity of the arteries with aneurisms and dissection, hypertelorism, CP

Congenital Myotonic Dystrophy

VPI, lingual myotonia, CP, occlusion issues

Oculo-auriculo-vertebral spectrum (Hemifacial microsomia / Goldenhar)

CPO MC, HM R side, epibulbar dermoid, males

Cornelia de Lange Syndrome

similar to FAS except w hair (eyebrows- synophyrs, hypertrichosis, eyelashes)

Patau Syndrome (trisomy 13)

females 1:10000 nondysjunction, maternal age

Kabuki Syndrome

arched eyebros, long eyelashes, long opening of eyelids, flat broad noase, large protruding ears
seizures, microcephaly, CP, high arched palate, scoliosis

Van der Woude

IRF 6 mutation
CL/CP or CPO
lower lip pits
hypodontia, narrow palate
syndactly

Waardenburg Syndrome

deafness, CL/CP, laterally displaced inner canthi (hypertelorism), heterochromis of iris, synophyrs
somtimes AR mostly AD

Cat eye syndrome

CP, micrognathia, coloboma of iris, retina, CHD, strabismus, down slanting palpebral fissures, anal atresia

Oto-palato-digital syndrome

CP, 4 types, frontal bossing, short stature, hyperteloris,, conductive hearing loss, broad distal planges (tree frog)
X-linked dominant - filamin A mutation
"boxer-like appearance

X-Linked CP w/ or w/o Ankyloglossia

TBX22 Xq21 mutation
incomplete CP, bifid uvula, rare
X-linked recessive

Pierre Robin Sequence

Mandibular hypoplasia-->glossoptosis, U-shaped cleft soft palate. --> airway obstruction
1:8500 most nonsyndromic
tooth agenesis - mand 2PM

teratogens for PRS

antiepileptics - hydantoin
anticonvulsants - trimethadione
FAS

syndromes related to PRS

stickler and VCFS

developmental PRS causes

meckles cartilage and mand outgrowth - SOX9 hypotonia

Stickler Syndrome (Hereditary Agressive Arthro Opthalmopathy)

flat face, eye abnormalities, hearing loss, joint problems
1: high risk of retinal detachment
2: eye abnormalities
3: no eye abnormalties
CP
crowding or teeth, retroclined incisors, OJ, OB, tooth agenesis
PRS

Velocardiofacial Syndrome

Catch22, TBX1, DiGeorge
PRS
cardiac abnormalities, CP, abnormal facies, hypocalcemia, hypoparathyroidism, thymic aplasia
VPI, squared nasal root, long face, microcephaly, absent adenoid

Hemifacial Microsomia (OAVS)

cardiac, vertebral, CNS defects
right side, males MC
sporadic MC transmission
butterfly vertebrae, scoliosis, kyphosis, rib anomalies

Goldenhar Syndrome (OAVS)

epibulbar dermatoids, inferior displacement of lateral canthus, upper lid coloboma, verebral anomalies
post open bite, vertical deficiencies, crowding on affected side

Treacher Collins Syndrome

TCOF1 mutation, but usually sporadic
treacle impt for rRNA production
bilateral, facial bone hypoplasia (Mandible and zygoma), down slanting palpebral fissures, notching of lower eyelid, broad nose, auricular anomalies, max projection and overjet, anterio

Auricular Atresia or Microtia

underdeveloped pinna, hearing impairment
HM, goldenhar, treacher collins

Anencephaly

dietary folate deficiency
maternal diabetes or obesity
anti-siezure meds
MTHFR gene - folate metabolism mutation

Microcephaly

zika, rubella, PKU, hypoxia
1:850-5000

hydrocephalus

1:500
X-linked (8%) recessive for L1CAM - lots of other causes
irritability, sleepy, vomitting, sunset eyes, seizures

Cleidocranial Dysplasia

brachycephaly, hypertelorism
1:1,000,000
RUNX2 mutation
delay in secondary dentition, peg shaped teeth, supernumerary teeth, malocclusion

Craniosynostosis

the premature fusing of the skull bones
1:1800-2500
increased ICP, blindness, cognitive disabilities not agreed on
CP, max protrusion and hypoplasia, cross bites, impaction, crowding, agenesis
FGFR, TWIST, FGF mutations

MC suture to fuse

saggital (scaphocephaly) narrow and long
45% of the time - males

Rarest sutures to fuse

metopic (25%)and lambdoid

coronal suture

unicoronal (25%) - 3:2 F

Craniosynostosis syndromes

Aperts(2), Crouzan(2), Muenke(3), Pfeiffer(1, 2) (FGFR1-3)
Sathre-Chotzen (TWIST)

Apert's Syndrome

FGFR2
syndactyly, coronal fusion, sunken mid-face, buldging eyes, crowded teeth,
1:65000-85000

Crouzan Syndrome

FGFR2 (sometimes 1 and 3)
multiple sutures, hypertelorism, bulging of the eyes, vision problems, shallow eye sockets, strabismus, beaked nose
hearing loss bc narrow canals, some CL/CP, posterior bilateral crossbite
1:62,500

Muenke Syndrome

FGFR3
coronal suture fusion, hypertelorism, flattened cheek bones, hearing loss
1:30,000

Pfeiffer syndrome

FGFR1 or FGFR2
coronal suture fusion, thumbs and big toes have brachydactyly and clinodactyly, bludging eyes, hyperteloris,, syndactyly, enlarged forehead
Type 1: norm lifespan
Type 2: cloverleaf head, more severe CNS, limited and delayed brain growth and

Saethe-Chotzen Syndrome

TWIST1
coronal suture fusion, high forehead, low frontal hairline, ptosis, low set ears
1:25,000-50,000