Phenotypes Flashcards Preview

Inheritance and postnatal diagnosis > Phenotypes > Flashcards

Flashcards in Phenotypes Deck (30)
Loading flashcards...
1

Prader willi syndrome

loss of paternal genes at 15q11-13

hypotonia as baby and failure to thrive
hyperphagia resulting in obesity
mild to moderate MR
small hands and feet
short
behavioural problems eg tantrums, poor peer interactions
hypogonadism

2

Angelman syndrome

loss of maternal genes at 15q11-q13

severe mental retardation
absent speech
ataxia
wide open mouth, prominent chin, protruding tongue
seizures
tongue thrusting
hyperactive
happy demeanor, laughing, smiling, hand flapping, fascination with water

3

Monosomy 1p36

1 in 5000. Candidate genes: KCNAB2, SK1.

dev del
hypotonia
delayed/absent speech
growth retardation
eye defects
anomalies of hands and feet
hearing loss
seizures
cardiac defects
microcephaly, frontal bossing, unusual ears, pointy chin, deep set eyes, straight eyebrows

4

Wolf hirschhorn syndrome

4p16.3 deletion. Loss of WHSC1 gene.

growth delay
mental retardation
seizures
Greek warrior helmet - hypertelorism, prominent glabella, high forehead, short philtrum
midline defects e.g. agenesis of corpus callosum, cleft palate, hypospadias.


mild form: <3.5Mb. MR is milder, more fluent language, major malformations uncommon
classical form: 5-18Mb. severe psychomotor delay, speech and walking
severe form: 22-25Mb. severe malformations.

5

1q21 deletions/duplications classes.

Class I - distal 1q21.1 del/dup. Smaller at ~1.8Mb
Class II - larger, 2.7Mb. Includes TAR region and distal 1q21.1.

6

TAR syndrome

Thrombocytopenia absent radius syndrome (TAR). Proximal 1q21.1.

Inheritance is a compound inheritance model. Often del in one allele and mutation in the other.
Candidate gene: RBM8A.

Features:
- absent radii with presence of thumbs
- congenital or early onset thrombocytopenia that can resolve in childhood.
- short or absent ulna and/or humerus
- malformations of hip or knee
- heart defects e.g. ASD, TOF
- renal abns

7

Mosaic trisomy 2 prenatally

Found at CVS but not at AF: outcome usually normal, although there may be IUGR.

Found at AF: greater risk of abns. Cases of IUGR and physical abns, IUD or stillbirth.

8

2p15-16 deletion syndrome

Candidate genes: VRK2 and BCL11A

Microcephaly
Severe speech delay
Moderate motor delay
Vision problems
Kidney problems

9

2p16.3 deletion

Candidate gene: NRXN1
Can be inherited from a normal parent, suggesting reduced penetrance or variable expressivity.

Autism and schizophrenia
Severe language delay
Hypotonia
Seizures

10

2q13 deletion

Genes: NPHP1. If homozygous deletion associated with:

- Joubert syndrome
- Nephronophthisis type 1

In heterozygous form, generally considered benign.

11

Mowat Wilson syndrome

Deletion of 2p22.
Gene: ZEB2

Hirschsprung disease
Genitourinary abns
Congenital heart defects
Agenesis of the corpus callosum

12

Waardenburg syndrome type 2

3p14. Loss of MITF gene.

hearing loss
changes in pigmentation of hair, skin and eyes

13

von Hippel Lindau

3p25-p26

autosomal dominant loss or mutation of VHL TSG gene
patients inherit one del/mut then second hit occurs in tumour cells
Develop several benign or malignant tumours in many organs
Renal carcinoma occurs in 70% of individuals and is the leading cause of mortality.

14

Blepharophimosis, ptosis and epicanthus inversus (BPES)

Mutation of FOXL2 at 3q22.3, autosomal dominant

Blepharophimosis - narrowing of the eye opening
eyelids cannot fully open and may have limited vision
Type I BPES associated with female infertility/ovarian failure.

15

4q21 microdeletion syndrome

Genes: PRKG2, RASGEF1B

Neonatal muscular hypotonia
Severe motor retardation
Marked growth restriction
Absent or delayed speech
Frontal bossing, large forehead

16

Facioscapulohumeral muscular dystrophy (FSHD)

Autosomal form of muscular dystrophy.
4q35 deletions associated with loss of D4Z4.
Muscle weakness and atrophy that occurs over time.

17

Cri du chat

5p deletion. Critical region is at 5p15.3 to 5p15.2, but can be whole arm.
Candidate genes: SEMA5A and CTNND2.

80% de novo
15% balanced familial rearrangement
Deletion size: 5-40Mb.

Features:
cat like cry (high pitched) in infants, due to abn of the larynx.
microcephaly
low birth weight
hypotonia
severe MR and psychomotor delay.
Distinctive facies: hypertelorism, rounded face, epicanthic folds, low set ears.

18

Sotos syndrome

5q35 deletion. Loss of NSD1 gene.
Not cytogenetically detectable
95% de novo.

Features:
excessive growth during 2nd and 3rd years of life, giving large body size
Macrocephaly
Large hands and feet
Advanced bone age
Learning disability - variable.
Cranial abns
Normal life expectancy

Diagnosis by: MLPA or array. Not readily detectable by sequence analysis or karyotyping.

Microduplication of the gene results in short stature.

19

5q14.3 deletion syndrome

Loss of MEF2C. Plays a role in synaptic plasticity.

Severe MR and devdel
Absent speech
Autism
Epilepsy
Severe hypotonia

Rett like syndrome as MEFC2 and MECP2 share the same pathway.

20

Cornelia de Lange syndrome

5p13.2 deletion with loss of NIPBL gene.
60% have mutation in NIPBL gene
99% are de novo
Testing strategy: sequence analysis. If no mut, do arrays for dup/del

Slow pre and postnatal growth
Intellectual disability (severe to profound)
Autistic spectrum or self destructive behaviour
Skeletal abs e.g syndactyly
Arched eyebrows that grow together (synophyrs)

21

6q11-q14 deletion

Candidate gene: COL12A1

hypotonia
short stature
limb/skeletal abns
umbilical hernia
devdel

22

Interstitial 6q24-6q25 deletion

Candidate gene: TAB2

Cardiac defects (ASD, VSD)
short stature
IUGR
agenesis of corpus callosum
hearing loss

23

Spinocerebellar ataxia 1 (SCA-1)

Expanded CAG trinucleotide repeat

24

Mosaic trisomy 9

Rare

growth retardation
severe MR
heart and renal abns
limb dislocations
microopthalmia

25

Trisomy 9p

is compatible with long term survival

growth retardation
MR
brachycephaly
microcephaly
hand abns - clinodactyly, single palmar crease

26

Tetrasomy 9p

Presence of isochromosome 9p
Ventroculomegaly prenatally
dysmorphism - cleft palate, hypertelorism, bulbous nose
devdel
growth delay
cardiac abns

27

9p deletion syndrome

Alfi's syndrome
Breakpoints from 9p22 to 9p24
Candidate genes: CER1, FOXD4, DOCK8

Moderate to severe MR
Depressed temples
Speech impairment
Abnormal genitalia

9p24 deletions only - XY gonadal dysgenesis (DMRT1 gene).

28

Kleefstra syndrome

9q34 deletion
Loss of all of part of EHMT1 gene (smallest deletion was 40kb)

Hypotonia
Behavioural problems - abnormal sleep patterns, autism, self injury
Pulmonary infections
Renal abns
Genital defects
Epilepsy

29

Chromosome 9 ring

Rare

Microcephaly
Micrognathia
Growth retardation
Moderate to severe MR (however some in normal range)
Hypospadias

30

2q32-q33

Gene: SATB2

- cleft lip/palate
- growth retardation
- feeding difficulties