Chap 14: Developmental Genetics and Birth Defects Flashcards

1
Q

Craniosynostosis

proptosis

large toes turned inward

thumbs point away

cloverleaf skull

A

Pfeiffer syndrome

  • FGFR1* - mild
  • FGFR2* - mild to severe

Gain of function mutations

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2
Q

Craniosynostsis

toes everted

TWIST

Loss of function mutation

A

Sarthre-Chitzen Syndrome

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3
Q

Craniosynostosis

fusion of metacarpels and metatarsal bones

most common syndromic craniosynostosis

p.Pro250Arg

A

Muenke Syndrome

Autosomal dominant- variable phenotype

FGFR3

Hearing loss in 72%

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4
Q

Bilateral coronal synostosis

brachycephaley

synostosis of the fingers and toes

A

Apert Syndorme

FGFR2

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5
Q

Craniosynostosis

Normal Intelligence

A

Crouzon Syndorme

FGFR2

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6
Q

X linked

Craniosynostosis

+/- cleft lip

females more severly affected than males

A

Craniofrontonasal Syndrome

EFNB1

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7
Q

What is exclusive about de novo fibroblast growth factor receptor mutations

A

Paternal origin

increases with paternal age

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8
Q

Defect of the developing forbrain

prosencephalon

A

Holoprosencephaly

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9
Q

Period of development when holoprosencehphaly takes place

A

gastrulation

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10
Q

Single central inciser

A

Holoprosencephaly

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11
Q
  • SHH*
  • ZIC2*
  • SIX3*
  • TGIF*
  • FGFR1*
A

Most common genes associated with holoprosencephaly

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12
Q

Most common envoronmental/maternal factor associated with holoprosencephaly

A

Uncontrolled DM

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13
Q

Birth Defect

caused by external mechanical forces

mechanical stress

low recurrance risk

usually in the last trimester

A
  • Deformations
  • Ex. Twins
  • Uterine abnormality
  • Reduced amniotic fluid
  • Potter sequence
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14
Q

Birth defect

occurs in structure that were forming normally

extrinsic breakdown

A
  • Disruptions
  • Amniotic band
  • Limb-body wall complex
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15
Q

Birth Defect

abnormal celllular orginization and function

involves one tissue type

A
  • Dysplasia
  • ex: ectodermal dysplasia
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16
Q

Birth Defect

Abnormal development

permanat change

intrinsic abnormality

can involve multiple tissue types

A

Malformations

cleft lip and palate

holoprosencephaly

17
Q

Birth Defect

localization of multiple defect

develop from same embryonic field

A
  • Complex
  • Example: OEIS complex (Ompalocele-Exstrophy-Imperforate Anus-Spinal defects)
  • Example: Pentalogy of Cantrell: Inferior sternal defect, anterior diaphragmatic defect Ompalocele cardiac defect
18
Q

recognizable pattern with a predictable natual history

19
Q

Pattern of anomalie

result from a single identifiable event

A
  • Sequence
  • Ex: Potter sequence–> Low amniotic fluid
  • Pierre-Robin Sequence–>Early mandibular hypoplasia–>posterior displacement of tough–>cleft palate
  • Poland Sequence–>Hypoplasia of the pectoralis major muscle secondary to a vascular disruption
20
Q

phenotypic similarities

distinct mutation or different genetic mechanism

A

Heterogeneity

21
Q

Multiple phenotypic (organs) effected

single gene alteration

effects are not obvious

A

Pleitrophy

ex: charge syndrome, pancreatic insufficiency in CF

22
Q

Radial Ray Defects

increase risk for AML, Myelodysplastic syndrome

A

Fanconi Anaemia

23
Q

Radial ray defects

upper limbs

Heart : VSD, ASD, conduction defects

thumbs: absent, small or triphalangeal, bifid

phocomelia

A

Holt-Oram Syndrome

Autosomal dominant

TBX5

24
Q

Radial Ray defects

1q21.1 microdeletion

preservation of thumbs

A

TAR

Thrombocytopenia abcent radius syndrome

RBM8A

25
Radial Ray defect Red cell aplasia
Diamond-Blackfan Anaemia
26
Radial ray defects anal atresia thumb abnormalities
Townes-Brock syndrome Autosomal dominant *SALL1*
27
Central or postaxial polydactly hypothalamic harmartoma bifid epiglottis, laryngeal cleft, pulmonary segmentation anomalies
Pallister-Hall * GLI3* * A*utosomal recessive frameshift/nonsense truncation mutations 3' of zinc finger to codon 1161, repressor
28
Preaxial polydactyly of feet postaxial polydactyly of hands macrocephaly, wide spaced eyes, broad nasal root
Greig cephalopolysyndactyly 5' or inclusive zinc finger domain Autosomal dominant
29
preaxial polydactyly of the feet post axial polydactyly of the hands macrocephaly wide spaced eyes broad nasal root intellectual disability Seizures
Greig cephalopolysyndactly contiguous gene syndrome deletion in chromosome 7(p13–p14).