GDA Craniofacial.txt

• Trisomy 13 or Patau’s Syndrome
• deformation of brain

• Trisomy 13 or Patau’s Syndrome
• small eyes

• Incidence 1 in 20,000 to 25,000 births
• 50% die in first month
• Associated with advanced maternal age
• 20% due to unbalanced translocation
• Holoprosencephaly
• Cleft lip and/or palate
• Cutis aplasia congenita
• Congenital heart defects
• Postaxial polydactyly
• Growth retardation
• Severe mental retardation
• Cleft lip and palate
• Microphthalmia
• Iris coloboma
• Postaxial polydactyly
• Congenital heart defects
• Urogenital defects
• Rockerbottom feet
• CNS malformations
• Holoprosencephaly
• Encepholoceles

• Trisomy 13
• abnormality on the back of the head

• -much overlap btw trisomy 13 and 18; this is why we do karyotype or similar testing
• -all trisomies related to increased maternal age, pts will be very thin (difficulty gaining weight)
• -hypotonicity when baby (“floppy”), but become stiff with advancing age (hypertonicity)
• -ear helix is malformed, small lower jaw, characteristic clenching of the hands, rocker bottom feet (back of heel of foot is like part of a rocking chair)
• -critical region- must be present in triplicate in order to have trisomy 18

• Most common chromosome disorder
• Most common genetic cause of moderate mental retardation
• 1 in 800 livebirths
• Associated with Maternal age (>35y)
• 1/1250 for 15-19 year old Mom
• 1/100 for 40 year old Mom

• Trisomy 21
• 90% maternal – meiosis I
• 10% paternal meiosis II

• Hypotonia
• Short stature
• Brachycephaly
• Congenital heart disease
• Duodenal atresia
• Tracheoesophageal fistula
• 15- fold increase for leukemia

• IRF 6 mutations
• Autosomal dominant (risk in family is %50)
• Cleft lip, cleft palate, lower lip pits

-pterygiums (webbing) in area of knee or elbow- mobility affected; if surgery performed, must be careful bc arteries, veins, & nerves can be carried in farthest part of webbing

• (1q32-41)(AD mutation)
• Van der Woude (lip pit/clefting syndrome)
• Popliteal pterygium / lip pit syndrome
• Gene causes 6% of non-syndromic cleft lip / cleft palate

• Ethyl alcohol
• Diphenylhydantoin
• Trimethadione
• Retinoids (for acne)
• Aminopterin and methotrexate
• Hyperthermia
• Cigarette smoking + TGF alpha

• Folic acid
• Avoidance of tobacco smoke
• At risk families
• Preconception folic acid
• High level ultrasound
• Genetic counseling

• Ectrodactyly-ectodermal dysplasia-cleft syndrome
• Also known as split hand-split foot-ectodermal dysplasia-cleft syndrome
• Ectodermal dysplasia, Facial clefting, ectrodactyly
• Selective tooth agenesis, microdontia, caries
• Hearing loss, small ears, malformed auricles
• Autosomal dominant mutations in the tumor protein p63 gene (TP63)
• ectrodactyly
• claw-like hand, 2nd/3rd digits may be missing
• ectodermal dysplasia
• hair, teeth, nails, sweat glands may all be abnormal

claw-like hand, 2nd/3rd digits may be missing

hair, teeth, nails, sweat glands may all be abnormal

• Velocardiofacial (VCF) syndrome, DiGeorge Syndrome
• Conotruncal heart defects
• 1 in 2,000 – 4,000
• Hypocalcemia – neonatal
• Developmental delay
• Psychiatric disorders
• Cleft lip and/or palate
• Thymic dysplasia – low T-cell numbers

• small jaw;
• this causes breathing difficulties (tracheotomy may be needed

• NOT SYNDROME
• Mandibular hypoplasia
• Tongue falls back and prevents normal developmental
• Closure of palate – cleft palate
• Neonatal upper airway obstruction – glossoptosis
• Primary defect – mandibular hypoplasia

• most common facial feature- lower eyelid looks droopy, as if there isn’t enough elasticity; there are also no eyelashes on lower eyelid; also cheek bones are small; down-slanting palpebral fissures (eyes slant downward)
• Mandibulofacial dysostosis
• 1 in 10,000 births
• Autosomal dominant with variable expressivity
• TCOF 1 gene on 5q32-33.1
• Protein treacle important in embryonic development – first brachial arch.
• Important in neural crest cell formation and proliferation
• Bilateral and symmetrical
• Hypoplastic mandible
• Hypoplastic supraorbital rims
• Hypoplastic zygoma
• Coloboma of eyelids
• Downward slanting eyes
• Micrognathia
• Cleft palate
• Malformed or absent ears - microtia
• Hearing loss
• Abnormal lower eyelids – eyelid colobomas
• Malar hypoplasia

• ranges from microtia (abnormality of external ear) to Goldenhar syndrome
• -hemifacial microsomia- where one side of face is smaller than other side; also may have facial nerve palsy, which is important to check for
• -OAV: aka Goldenhar syndrome
• epibulbar dermoids- extra tissue on corner of eye
• hemivertebrae- puts pts at risk for sculiosis
• genetic defect hasn’t been established yet, although looked for
• may be bilateral or asymmetric (for ex one or both eyes may not be able to be closed completely- can tell parents to use eye drops when sleeping)

• -vocab: stenotic- narrow; atretic- blind pouch
• -Grade 1 is milder (upper helix not completely formed), 2 is more severe (some tissue, may have auricular skin tag),

• Distinguish by looking at extremities
• Apert syndrome - 2-3 bilateral hand and foot syndactyly, mental retardation
• Crouzon syndrome – normal hands and feet
• Pfeiffer syndrome – abnormal thumbs and big toes (broad and medially deviated), + brachydactyly
• Muenke syndrome – normal thumbs, + broad toes, + carpal or tarsal fusion
• Crouzon syndrome with acanthosis nigricans (AN) – no abnormalities in hands or feet
• Jackson Weiss syndrome – variable hands, broad medially deviated great toes, abnormal tarsals
• Beare-Stevenson syndrome - no abnormalities in hands or feet
• FGFR2 Isolated coronal synostosis - no abnormalities in hands or feet

• involved in craniosynostosis syndromes
• -mutations tend to be in extracellular domain of protein (which binds ligand)

• Ventral forebrain maldevelopment
• Facial dysmorphism
• Hypotelorism
• Developmental delay
• 1 in 10,000-1 in 20,000 births
• Most common human congenital brain defect
• Male:female ratio 1:2
• Chromosomal causes
• Trisomy 13, 18
• Environmental/teratogens
• Maternal diabetes
• Single gene defects
• Sonic Hedge Hog (SHH)
• TGIF, ZIC2, SIX3, PTCH

• SHH
• First gene discovered to cause holoprosencephaly
• Autosomal dominant with variable expressivity
• Secreted signaling protein required for developmental patterning in mammals and insects
• Loss of function mutations

• Mild
• Single central incisor
• Moderate
• Hypotelorism
• Cleft lip and palate
• Severe
• cyclopia
• Alobar
• Most severe form
• Brain fails to separate into separate hemispheres
• One ventricle
• Semilobar
• Intermediate form
• Brain hemispheres have some separation
• Lobar
• Least severe
• Considerable separation of hemispheres

• Cranium bifidum
• Cephalocele
• Types
• Occitipal – 75%
• Parietal
• Anterior - (Frontonasal) increased risk in southeast Asia
• Cerebral “blowout”
• Point of least resistance
• Underlying cranium bifidum
• High frequency of hydrocephalus

• amniotic bands- can form anywhere (see picture); amniotic layer can be sticky, and attach to part of the fetus, amputating parts of the body (fingers, toes)
• Chromosomal
• Trisomy 13
• Trisomy 18
• Monogenic
• Meckel syndrome
• Walker-Warburg syndrome
• Disruptive
• Maternal hyperthermia
• Warfarin embryopathy
• Amniotic bands
• Associations
• Frontonasal dysplasia
• Oculoauricular vertebral syndrome (OAV)