DYSMORPHOLOGY

Question 1

• Single, local tissue morphogenesis abnormality that produces a chain of subsequent defects
• DiGeorge sequence of primary fourth branchial arch and 3rd and 4th pharyngeal pouch defects that lead to aplasia or hypoplasia of the thymus and parathyroid glands, aortic arch anomalies, and micrognathia

Answer 1

Malformation sequence

Question 2

• Mechanical (uterine) forces that alter structure of intrinsically normal tissue
• Oligohydramnios produces deformations by in utero compression of limbs (dislocated hips, equinovarus foot deformity), crumpled ears, dislocated nose, or small thorax

Answer 2

Deformation sequence

Question 3

• In utero tissue destruction Amnionic membrane rupture sequence after a period of normal sequence, leading to amputation of morphogenesis
• Amnionic membrane rupture sequence, leading to amputation of fingers/toes, tissue fibrosis, and
  destructive tissue bands

Answer 3

Disruption sequence

Question 4

• Poor organization of cells into tissues or organs
• Neurocutaneous melanosis sequence with poor migration of melanocyte precursor cells from the
  neural crest to the periphery, manifesting as melanocytic hamartosis of skin, meninges, and so
  forth

Answer 4

Dysplasia sequence

Question 5

• Appearance of multiple malformations in unrelated tissues without an understandable unifying cause; with enhanced genetic investigation, a single etiology may become identified
• Trisomy 21, Teratogens

Answer 5

Malformation syndrome

Question 6

• Mendelian autosomal recessive
• Abnormal vertebral segmentation
• Neural tube defects
• DLL3 mutations; mutations can also be present in other genes

Answer 6

SPONDYLOCOSTAL DYSOSTOSIS SYNDROMES

Question 7

• Autosomal semidominant
• Reduced or absent iris
• PAX6 mutations

Answer 7

ANIRIDIA

Question 8

• Autosomal semidominant
• Deafness
• White forelock
• Wide-spaced eyes
• Pale eye pigment
• PAX3 mutations
• MITF mutations

Answer 8

WAARDENBURG SYNDROME

Question 9

• Loss of function or heterozyg
• Microcephaly
• Cyclopia
• Single central incisor
• SHH mutations

Answer 9

HOLOPROSENCEPHALY

Question 10

• Chromosomal
• Mental retardation
• Characteristic dysmorphic features
• Congenital heart disease
• Increased risk of leukemia
• Alzheimer disease
• 50% increase of estimated 250 genes on chromosome 21
• Trisomy 21

Answer 10

DOWN SYNDROME

Question 11

• Multifactorial
• Meningomyelocele
• Defects in folate sensitive enzymes or folic acid uptake

Answer 11

NEURAL TUBE DEFECTS

Question 12

• Teratogenic
• Microcephaly
• Developmental delay
• Facial abnormalities
• Behavioral abnormalities
• Ethanol toxicity to developing brain

Answer 12

FETAL ALCOHOL SYNDROME

Question 13

• Teratogenic
• Microtia
• Congenital heart disease
• Isotretinoin effects on neural crest and branchial arch development

Answer 13

RETINOIC ACID EMBRYOPATHY

Question 14

Two major intrinsic causes of deformations

Answer 14

• primary neuromuscular disorders and oligohydramnios
• decreased amniotic fluid, which is caused by renal defects

Question 15

Are those that result in fetal crowding to restrict fetal movement

Answer 15

The major extrinsic causes of deformation

Question 16

• caused by destruction of a previously normally formed part
• 2 basic mechanisms
  > entanglement followed by tearing apart or amputation of a normally developed structure, usually a digit, arm, or leg, by strands of amnion floating within amniotic fluid (amniotic bands)
  > Interruption of the blood supply to a developing part, which can lead to infarction, necrosis, and/or resorption of structures distal to the insult

Answer 16

DISRUPTION

Question 17

• pattern-recognition approach
  > compares the manifestations in the patient against am enormous and memorized (or computerized) knowledge of human pleiotropic disorders
  = History
• pedigree or family history that is necessary to assess the inheritance pattern, or lack thereof
  > A 3-generation pedigree is sufficient for this purpose
• perinatal history is an essential component of the history
  > pregnancy history of the mother, factors that may relate to deformations or disruptions (oligohydramnios), and maternal exposures to teratogenic drugs or chemicals

Answer 17

DYSMORPHIC CHILD

Question 18

• those that either cause dysfunction (absence ofa digit) or require surgical correction (polydactyly)
• Those that cause neither significant dysfunction nor require surgical correction (mild cutaneous syndactyly)

Answer 18

• “major” birth defects
• “minor” birth defects

Question 19

are the most sensitive methods for the detection of cytogenomic alterations associated with multiple congenital anomalies

Answer 19

Array CGH and single-nucleotide polymorphism genotyping with copy number variation (dosage detection)