Phenotypes Flashcards
(30 cards)
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
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
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
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.
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.
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
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
Microcephaly Severe speech delay Moderate motor delay Vision problems Kidney problems
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
2q13 deletion
Genes: NPHP1. If homozygous deletion associated with:
- Joubert syndrome
- Nephronophthisis type 1
In heterozygous form, generally considered benign.
Mowat Wilson syndrome
Deletion of 2p22.
Gene: ZEB2
Hirschsprung disease
Genitourinary abns
Congenital heart defects
Agenesis of the corpus callosum
Waardenburg syndrome type 2
3p14. Loss of MITF gene.
hearing loss
changes in pigmentation of hair, skin and eyes
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.
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.
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.
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.
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.
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)
6q11-q14 deletion
Candidate gene: COL12A1
hypotonia short stature limb/skeletal abns umbilical hernia devdel
Interstitial 6q24-6q25 deletion
Candidate gene: TAB2
Cardiac defects (ASD, VSD) short stature IUGR agenesis of corpus callosum hearing loss
Spinocerebellar ataxia 1 (SCA-1)
Expanded CAG trinucleotide repeat
Mosaic trisomy 9
Rare
growth retardation severe MR heart and renal abns limb dislocations microopthalmia
