Phenotypes Flashcards
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
