Common Malformations Flashcards
What is the definition of a minor anomaly?
A developmental difference that may be important for diagnosis, but has no
physical impact
* Single palmar crease, clinodactyly
What is the definition of a major anomaly?
A congenital anomaly that causes a problem requiring medical or surgical
intervention
* Heart defect, cleft lip or palate, Hirschsprung
What is a deformation?
An external factor produces abnormal shape due to pressure and/or restriction of
growth and movement
* Club foot: Talipes equinovarus
* Can be due to fetal constraint
What kind of anomaly is talipes equinovarus “club foot”?
Deformation
What kind of anomaly is plagiocephaly?
Deformation
What is a disruption?
A disruption implies an interruption to the developmental process
* Interpreted in different ways
* Vascular interruptions
* Maternal exposures
* Alcohol
* Medications
* Similar to deformation, the developmental process would have been normal
What kind of process is phocomelia from thalidomide?
Disruption
What kind of process is Klippel Feil (non-separation of cervical vertebrae? What is thought to cause it?
Disruption.
Majority sporadic. Hypothesized to be “Subclavian Artery Supply Disruption Sequence”
What kind of process is involved with Moebius?
Disruption
Bilateral facial and abducens nerve palsies. “Cross-eyed”
What kind of process is involved with Poland syndrome (absence of pectoralis, breast hypoplasia, missing ribs)?
Disruption
What kind of process is involved with Hemifacial microsomia (Goldenhaar syndrome)?
Disruption
What is a malformation?
A malformation is birth anomaly in which the developmental instructions were incorrect
What is dysplasia?
Abnormal cell type, differentiation, or growth
* Often used with cancer
What is hyperplasia?
Excessive growth
What is hypoplasia?
Inadequate growth
What is atrophy?
A normal structure shrinks over time
What kind of growth process is seen with Beckwith Wiedemann Syndrome?
Macroglossia and hemihypeplasia
What is a sequence?
- “One thing leads to another”
- Can involve multiple mechanisms, including malformation,
disruption, and deformation
What are the features of PIERRE ROBIN SEQUENCE?
- Small mandible
- Tongue displaced posteriorly
- Tongue blocks the fusion of the
palate in the midline - Severe cases: Tongue impairs
formation of larynx
What are the two most common disorders with Pierre Robin sequence?
Stickler Syndrome (25% of PRS)
Deletion 22 syndrome
What is an association?
A collection of anomalies that are
recognized to be co-occurring at
higher-than-expected statistical
chance
e.g. VACTERL (no genetic cause)
What does VACTERL stand for?
- V: Vertebral
- A: Anorectal malformation
- C: Cardiac
- T: Tracheo-esophageal atresia/fistula
- E: Ear anomaly
- R: Renal anomaly
- L: Limb (radial ray / thumb side)
What is MURCS association?
- Mullerian
- Ureteral
- Renal
- Cervicothoracic
- Somite abnormalities
- Uterine anomalies, fallopian tube abnormalities
- Vas deferens anomalies in males
- Cervical vertebral fusions—Klippel Feil. Also can have Sprengel
- Hearing loss
What is the result of failure of fusion of maxillary prominences to the medial nasal prominence?
Cleft lip/cleft palate
What is gastroschisis?
- Protrusion of intestines through the abdominal wall
- Believed to be a disruption event
- Interruption of the omphalomesenteric artery (PMID: 6450826)
What is gastroschisis associated with?
Trisomies (~1%)
Young maternal age, smoking, alcohol, vasoactive medications
What is an omphalocele?
Protrusion of intestines, but with covered sac onto which umbilical cord attaches.
* Developmental anomaly—intestines are not properly pulled back into the abdomen
* Seen with chromosomal disorders and Beckwith-Wiedemann syndrome (imprinting)
* Large omphaloceles involving liver, etc, point to trisomy 18 and others.
What is craniosynostosis?
Premature fusion of one or more cranial sutures.
Typically present at birth
Diagnosed by x-ray or CT scan
What other systems do you look at with craniosynostosis syndrome?
Look at the hands and feet
What genes are responsible for the most common causes of craniosynostosis?
FGFR1 (Pfeiffer)
FGFR2 (Apert syndrome)
FGFR3 (Muenke syndrome, Pfeiffer)
Gain of function
TWIST: Saethre Chotzen (LoF, deletion)
What are the genes responsible for Pfeiffer syndrome and what is the phenotype?
FGFR1, FGFR2 (AD)
Type 2: Cloverleaf skull
Large thumb
Large toes, toe fusion
Can have ID
What is the gene responsible for Apert syndrome and what is the phenotype?
- FGFR2 (AD)
- Craniosynostosis (Bilateral coronal)
- “Mitten hand” malformation (Complex syndactyly)
Associated anomalies:
* Hearing loss
* Intellectual disability
* CNS malformations
* Choanal stenosis (narrow nasal passage)
* Tracheal anomalies – “tracheal sleeve”
What is the gene responsible for Crouzon syndrome and what is the phenotype?
FGFR2 (AD)
- Normal hands
- Midface hypoplasia leads to shallow orbit
- Proptosis
- Risk for blindness
- Narrow, sometimes beaked, nose
- Usually normal development
- Hearing loss
What is the gene responsible for SAETHRE-CHOETZEN syndrome and what is the phenotype?
TWIST, FGFR2 (AD)
- Craniosynostosis
- Facial asymmetry
- Ptosis
- Small, rotated ears
- Brachydactyly, mild hand and foot anomalies
