Flashcards in Phenotypes Deck (30)
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
behavioural problems eg tantrums, poor peer interactions
loss of maternal genes at 15q11-q13
severe mental retardation
wide open mouth, prominent chin, protruding tongue
happy demeanor, laughing, smiling, hand flapping, fascination with water
1 in 5000. Candidate genes: KCNAB2, SK1.
anomalies of hands and feet
microcephaly, frontal bossing, unusual ears, pointy chin, deep set eyes, straight eyebrows
Wolf hirschhorn syndrome
4p16.3 deletion. Loss of WHSC1 gene.
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.
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.
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.
- 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
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.
2p15-16 deletion syndrome
Candidate genes: VRK2 and BCL11A
Severe speech delay
Moderate motor delay
Candidate gene: NRXN1
Can be inherited from a normal parent, suggesting reduced penetrance or variable expressivity.
Autism and schizophrenia
Severe language delay
Genes: NPHP1. If homozygous deletion associated with:
- Joubert syndrome
- Nephronophthisis type 1
In heterozygous form, generally considered benign.
Mowat Wilson syndrome
Deletion of 2p22.
Congenital heart defects
Agenesis of the corpus callosum
Waardenburg syndrome type 2
3p14. Loss of MITF gene.
changes in pigmentation of hair, skin and eyes
von Hippel Lindau
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.
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.
4q21 microdeletion syndrome
Genes: PRKG2, RASGEF1B
Neonatal muscular hypotonia
Severe motor retardation
Marked growth restriction
Absent or delayed speech
Frontal bossing, large forehead
Facioscapulohumeral muscular dystrophy (FSHD)
Autosomal form of muscular dystrophy.
4q35 deletions associated with loss of D4Z4.
Muscle weakness and atrophy that occurs over time.
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.
cat like cry (high pitched) in infants, due to abn of the larynx.
low birth weight
severe MR and psychomotor delay.
Distinctive facies: hypertelorism, rounded face, epicanthic folds, low set ears.
5q35 deletion. Loss of NSD1 gene.
Not cytogenetically detectable
95% de novo.
excessive growth during 2nd and 3rd years of life, giving large body size
Large hands and feet
Advanced bone age
Learning disability - variable.
Normal life expectancy
Diagnosis by: MLPA or array. Not readily detectable by sequence analysis or karyotyping.
Microduplication of the gene results in short stature.
5q14.3 deletion syndrome
Loss of MEF2C. Plays a role in synaptic plasticity.
Severe MR and devdel
Rett like syndrome as MEFC2 and MECP2 share the same pathway.
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)
Candidate gene: COL12A1
Interstitial 6q24-6q25 deletion
Candidate gene: TAB2
Cardiac defects (ASD, VSD)
agenesis of corpus callosum
Spinocerebellar ataxia 1 (SCA-1)
Expanded CAG trinucleotide repeat
Mosaic trisomy 9
heart and renal abns
is compatible with long term survival
hand abns - clinodactyly, single palmar crease
Presence of isochromosome 9p
dysmorphism - cleft palate, hypertelorism, bulbous nose
9p deletion syndrome
Breakpoints from 9p22 to 9p24
Candidate genes: CER1, FOXD4, DOCK8
Moderate to severe MR
9p24 deletions only - XY gonadal dysgenesis (DMRT1 gene).
Loss of all of part of EHMT1 gene (smallest deletion was 40kb)
Behavioural problems - abnormal sleep patterns, autism, self injury
Chromosome 9 ring
Moderate to severe MR (however some in normal range)