Genetic conditions relevant to psychiatry Flashcards
Mutation present in DiGeorge syndrome
22q11.2 deletion - microdeletion of ~30-40 genes on the long arm of chromosome 22
Percentage of cases of DiGeorge syndrome which are due to de novo deletion
10%
Inheritance pattern for cases of DiGeorge syndrome which are inherited
Autosomal dominant
Risk of a child of one affected parent and one unaffected parent inheriting DiGeorge syndrome
50%
Percentage of patients with DiGeorge syndrome who develop schizophrenia
25%
Features of DiGeorge syndrome
Congenital heart disease Cleft palate Mild-moderate learning difficulties Hypocalcaemia due to hypoparathyroidism Small thymus and immunodeficiency Psychosis Hearing difficulties Swallowing difficulties
Mutation present in Williams syndrome
7q11 microdeletion
Inheritance pattern of inherited cases of Williams syndrome (small percentage of total cases; most are de novo deletions)
Autosomal dominant
Psychological and cognitive features of Williams syndrome
Moderate intellectual disability Specific visuospatial difficulties Lack of social inhibition Higher than expected verbal skills for IQ Anxiety Increased rate of autism and ADHD
Physical features of Williams syndrome
Broad forehead Elf-like facial appearance Epicanthic folds Small jaw Large mouth and tongue
Medical conditions associated with Williams syndrome
Hypercalcaemia
Supravalvular aortic stenosis
Hyperacusis
Abdominal pain
Mutation occurring in Smith-Magenis syndrome
17p11.2 microdeletion
Behavioural and psychological features of Smith-Magenis syndrome
Disrupted sleep patterns
Self injury behaviours
Self hugging
Moderate to severe learning disability
Physical features of Smith-Magenis syndrome
Broad, square face
Deep set eyes
Heavy eyebrows
Full lips
Mutation occurring in Angelman syndrome
15q11-13 deletion maternally inherited
Features of Angelman syndrome
Severe intellectual disability Speech impairment - little spoken language compared to expected for developmental stage Tremulous limb movements and ataxia Frequent laughing, happy demeanour Seizures Uplifted, flexed arms when walking
Mutation occurring in Prader-Willi syndrome
15q11-13 deletion paternally inherited
Features of Prader-Willi syndrome at birth
Hypotonia
Low birth weight
Feeding difficulties
Lethargy
Physical features of Prader-Willi syndrome
Small hands and feet Obesity Short stature Light skin and hair compared to family Thin top lip Downturned mouth Reduced sexual development
Developmental and behavioural features of Prader-Willi syndrome
Mild/borderline intellectual disability Poor spoken language Hyperphagia Skin picking Poor coordination
Mutation occurring in Cri-du-chat syndrome
5p deletion
Non-facial features of cri du chat syndrome
High pitched cry Difficulty swallowing and feeding Low birth weight and poor growth Hyperactivity and aggression Repetitive movements Severe intellectual disability Poor speech
Facial features of cri du chat syndrome
Microcephaly Epicanthic folds Round face Small chin Low set ears Wide set eyes
Mutation present in Wolf-Hirschborn syndrome
4p16 deletion
Features of Wolf-Hirschborn syndrome
Severe intellectual disability
Growth impairment
Seizures
‘Greek warrior helmet’ face
Inheritance pattern of Rubinstein-Taybi syndrome
Autosomal dominant
Mutation present in Rubinstein-Taybi syndrome
16p13.3 microdeletion
Features of Rubinstein-Taybi syndrome
Short stature Moderate to severe intellectual disability Broad thumbs and first toes Undescended testes in males Microcephaly Complications from anaesthesia
Chromosome pattern seen in Turner syndrome
45 X0
Chromosome pattern seen in Klinefelter syndrome
47 XXY
Chromosome pattern seen in Jacob’s syndrome
47 XYY
Features of Jacob’s syndrome
Intellectual disability
Tall stature
Normal fertility and sexual development
Behavioural issues (thought to relate to intellectual disability and low socioeconomic status which is over-represented in Jacob’s syndrome)
Features of Klinefelter syndrome
Infertility Reduced body and facial hair Small testes Gynaecomastia Shy personality Mild intellectual disability
Inheritance pattern of tuberous sclerosis
Autosomal dominant - 2/3 of cases are de novo mutations
Sites of mutations causing tuberous sclerosis
9q34
16p13
Neurological and psychiatric features of tuberous sclerosis
Increased risk of brain tumours especially astrocytoma
Seizures
Hydrocephalus
Aggressive behaviour
Increased rate of autism and ADHD
Variable degree of intellectual disability
Dermatological features of tuberous sclerosis
Ash leaf macules
Shagreen patches
Facial angiofibromas
Ungual fibromas - small tumours under the toenails and fingernails
Non-neurological or dermatological features of tuberous sclerosis
Benign kidney tumours
Benign cardiac tumours
Retinal hamartomas
Inheritance pattern of Treacher Collins syndrome
Autosomal dominant (usually - rare mutations can cause an autosomal recessive form)
Primary mutation site causing Treacher Collins syndrome
5q32
Features of Treacher Collins syndrome
Underdeveloped facial bones Small jaw and chin Cleft palate Airway collapse due to underdeveloped facial bones in severe cases Downward slanting eyes Absent or small ears Hearing loss Usually no intellectual disability
Inheritance pattern of Apert syndrome
Autosomal dominant - but almost all cases are sporadic
Mutation site for Apert syndrome
10q
Features of Apert syndrome
Craniosynostosis Syndactyly Polydactyly Mild to moderate intellectual disability Hearing impairment
Inheritance pattern of Noonan syndrome
Autosomal dominant
Most common mutation site for Noonan syndrome
12q24
Features of Noonan syndrome
Widely spaced eyes Low set and backward rotated ears Deeply grooved philtrum Short stature Congenital heart disease - especially pulmonary valvular stenosis Webbed neck Intellectual impairment
Inheritance pattern of Hurler syndrome
Autosomal recessive
Alternative name for Hurler syndrome
Mucopolysaccharidosis type I
Features of Hurler syndrome
Features usually become apparent in the first year
Short stature
Coarse facial features
Developmental delay beginning at ~1 year and deteriorating after 2-3 years
Clouded corneas
Death by around age 10
Mutation site for Hurler syndrome
4p16
Alternative name for Hunter syndrome
Mucopolysaccharidosis type II
Inheritance pattern of Hunter syndrome
X-linked recessive
Features of Hunter syndrome
Similar to Hurler syndrome
Coarse facial features
Developmental decline and loss of skills after 1-2 years
Death at a young age
Alternative name for Sanfilippo syndrome
Mucopolysaccharidosis type III
Inheritance pattern of Sanfilippo syndrome
Autosomal recessive
Features of Sanfilippo syndrome
Similar to the other mucopolysaccharidoses
Coarse facial features
Progressive loss of skills after age 1-2
Death at an early age
Inheritance pattern of Lesch-Nyhan syndrome
X-linked recessive
Site of mutation for Lesch-Nyhan syndrome
Xq26-27
Features of Lesch-Nyhan syndrome
Overproduction of uric acid
Kidney stones
Gout
Moderate intellectual disability
Self injury behaviours
Dystonia, hyperreflexia, spasticity - usually unable to walk
Death in first or second decade due to kidney failure
Deficient enzyme in Lesch-Nyhan syndrome
Hypoxanthine-guanine phosphoribosyltransferase
Inheritance pattern of Rett syndrome
X-linked dominant (but almost always de novo mutation)
Features of Rett syndrome
Affects females only - causes death in utero in males
Normal development until 6-18 months
Loss of skills and language after 18 months
Characteristic hand movements e.g. hand wringing
Development of seizures
Plateau stage until ~10 years
Motor deterioration after age 10
Inheritance pattern of MELAS syndrome
Mitochondrial
Full name of MELAS syndrome
Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes
Features of MELAS syndrome
Build up of lactic acidosis leading to vomiting, abdominal pain, fatigue
Stroke-like episodes with altered consciousness, seizures, altered vision and headaches
Risk of progressive brain damage due to the stroke-like episodes
Inheritance pattern of Leber’s hereditary optic neuropathy
Mitochondrial
Features of Leber’s hereditary optic neuropathy
Acute visual loss in one eye, with visual loss in the other eye weeks to months later, usually in young adulthood
Inheritance pattern of chronic progressive external ophthalmoplegia
Mitochondrial
Features of chronic progressive external ophthalmoplegia
Gradually worsening inability to move the eyes and eyebrows
Inheritance pattern of MERRF syndrome
Mitochondrial
Full name of MERRF syndrome
Myoclonic epilepsy with ragged red fibres
Inheritance pattern of Kearns-Sayre syndrome
Mitochondrial
Features of Kearns-Sayre syndrome
Chronic progressive external ophthalmoplegia Retinitis pigmentosa Cerebellar ataxia Proximal muscle weakness Deafness
Trinucleotide repeat seen in fragile X syndrome
CGG
Trinucleotide repeat seen in Friedreich’s ataxia
GAA
Trinucleotide repeat seen in Huntington’s chorea
CAG
Trinucleotide repeat seen in myotonic dystrophy 1
CTG
Inheritance pattern of Friedreich’s ataxia
Autosomal recessive
Deficient protein in Friedreich’s ataxia
Frataxin
Features of Friedreich’s ataxia
Start of symptoms in childhood Ataxia Dysarthria Loss of lower limb reflexes Heart problems including cardiomegaly Scoliosis Usually gradual loss of mobility leading to require a wheelchair by ~30
Inheritance pattern of fragile X syndrome
X-linked dominant
Male:female ratio of fragile X syndrome
2:1
Reason for fewer females being affected by fragile X syndrome
Females have another X chromosome which can compensate to some extent
Number of CGG repeats which generally leads to fragile X
> 52 - destabilises the area leading to further expansion during gamete production
Gene affected in fragile X syndrome
FMR1
State of people who carry the increased number of CGG repeats for fragile X syndrome but do not clinically have fragile X syndrome
Premutation carriers
Medical complications of male premutation carriers for fragile X
Intention tremor
Ataxia
Medical complications for female premutation carriers for fragile X
Premature ovarian failure
Mild cognitive disabilities
Physical features of fragile X syndrome
Large, protruding ears Long face Hyper flexibility Macro orchidism Hypotonia Cluttered speech
Behavioural and psychiatric features of fragile X syndrome
Autism in up to 60%
ADHD in most males
Moderate intellectual disability
Social anxiety
Inheritance pattern for Huntington’s disease
Autosomal dominant
Mutation site for Huntington’s disease
4p16.3
Protein affected in Huntington’s disease
Huntingtin
Usual age of onset of Huntington’s disease
30-50
Affected parent associated with increased anticipation in Huntington’s disease (due to greater repeat expansion during gamete production)
Father
Number of CAG repeats required to present with Huntington’s disease
> 35
Features of Huntington’s disease
Huntington's chorea Impairment of gross motor skills Difficulty swallowing Worsening cognition and eventually dementia Anxiety Depression Impulsivity
Inheritance pattern of myotonic dystrophy
Autosomal dominant
Features of myotonic dystrophy
Muscle weakness Early cataracts Heart disease including arrhythmias and conduction delays Frontal balding Bilateral ptosis
Diseases caused by a deletion on chromosome 15, differing due to genomic imprinting
Prader Willi syndrome - paternally inherited
Angelman syndrome - maternally inherited
Gene and chromosome affected in myotonic dystrophy 1
DMPK gene on chromosome 19
Inheritance pattern of Wilson’s disease
Autosomal recessive
Inheritance pattern of red green colour blindness
X-linked recessive
Inheritance pattern of haemophilia
X-linked recessive
Inheritance pattern of Duchenne muscular dystrophy
X-linked recessive
Inheritance pattern of Marfan’s syndrome
Autosomal dominant
Inheritance pattern of neurofibromatosis
Autosomal dominant
Chromosome affected in neurofibromatosis type I
17
Chromosome affected in neurofibromatosis type II
22
Features of neurofibromatosis type I
Café-au-lait spots on the skin
Axillary freckling
Neurofibromas
Behavioural difficulties
Features of neurofibromatosis type II
Acoustic neuromas leading to tinnitus and hearing loss
Young onset cataracts
Inheritance pattern of homocystinuria
Autosomal recessive
Laboratory findings for homocystinuria
Increased levels of homocysteine in the urine
Features of homocystinuria
Downward dislocation of the lens of the eye Short sightedness Intellectual disability Seizures Marfanoid habitus and pectus excavatum
Features of Marfan syndrome
Tall thin habitus with long arms and legs
Lens dislocation and short sightedness
Flexible joints
Cardiovascular complications especially valve prolapse and aortic aneurysm or dissection
Inheritance pattern of phenylketonuria
Autosomal recessive
Protein which has decreased metabolism in phenylketonuria
Phenylalanine
Features of untreated PKU
Seizures Intellectual disability Musty odour Fair hair and skin compared to family Microcephaly
Features of Duchenne muscular dystrophy
Proximal muscle weakness starting in early childhood
Gower’s sign
Calf pseudohypertrophy
Intellectual impairment in 30%
Inheritance pattern of Becker muscular dystrophy
X-linked recessive
Features of Becker muscular dystrophy
Symptoms start after age 10
Progressive weakness similar to DMD
Intellectual impairment less common than in DMD
Inheritance pattern of Coffin-Lowry syndrome
X-linked dominant
Features of Coffin-Lowry syndrome
Severe intellectual disability Sleep apnoea Drop attacks Flattened nose Downward sloping eyes Short stature
Inheritance pattern of Niemann-Pick disease
Autosomal recessive
Features of Niemann-Pick disease
Hepatosplenomegaly and abdominal distention
Ataxia
Dysarthria
Progressive loss of intellectual abilities and dementia type presentation
Gene and chromosome affected in Huntington’s disease
HTT gene on chromosome 4
Genes affected by tuberous sclerosis
TSC1
TSC2
Genes affected by tuberous sclerosis
TSC1
TSC2
Gene affected in Huntington’s disease
HHT/IT15 (alternative names for the same gene)
Features of CADASIL
Symptoms start aged 35-55 Migraines TIAs and strokes Mood disorders Later in life dementia and pseudobulbar palsy
Gene and chromosome affected in CADASIL
Notch3 gene on chromosome 19
Genetic cause of Cornelia de Lange syndrome
Spontaneous mutation in vast majority of cases
500 genetic mutations associated
Clinical features of Cornelia de Lange syndrome
Long and thick eyebrows Short nose Downturned mouth Long, smooth philtrum Intellectual disability Microcephaly Autistic behaviours
Alternative name for Wilson’s disease
Hepatolenticular degeneration
Features of Wilson’s disease
Features of liver disease - varices, ascites, spider angiomata, fulminant liver failure
Cognitive decline
Seizures
Depression, anxiety, psychosis
Kayser-Fleischer rings on slit lamp examination
Ages of patients with Wilson’s disease presenting with neuropsychiatric symptoms vs. liver symptoms
Patients presenting with liver symptoms present younger
Inheritance pattern of CADASIL
Autosomal dominant
Features of triple X syndrome
May have no features
Usually normal sexual development and fertility
Often global developmental delay
Tall stature
Enzyme affected in PKU
Phenylalanine hydroxylase
Features of Kallmann syndrome
Hypogonadotropic hypogonadism - infertility, poorly defined secondary sexual characteristics
Anosmia
Condition associated with mutations in the Kiss1 gene
Kallmann syndrome
Inheritance pattern of Tay-Sachs disease
Autosomal recessive
Ethnic group with increased risk of Tay-Sachs disease
Ashkenazi Jews
Gene and chromosome affected in Tay-Sachs disease
HEXA gene, chromosome 15
Features of infantile Tay-Sachs disease (most common form)
Loss of motor abilities at 3-6 months
Seizures
Hearing loss
Death by age 3-5
Disease characterised by idiopathic basal ganglia calcification
Fahr disease
Clinical features of Fahr disease
Clumsiness
Involuntary movements
Gait disturbance
Psychosis and cognitive impairment
Inheritance pattern of Fahr disease
Autosomal dominant
Age Fahr disease typically presents at
40-60
Distinction sometimes made between Fahr disease and Fahr syndrome
Fahr disease is the autosomal dominant genetic disease causing basal ganglia calcification
Fahr syndrome is basal ganglia calcification due to secondary causes
Chromosome affected in myotonic dystrophy
19
Inheritance pattern of haemochromatosis
Autosomal recessive
Inheritance pattern of Leigh syndrome
Mitochondrial
Most common cause of death among patients with Down syndrome
Heart disease
Enzyme deficient in Niemann-pick disease
Sphingomyelinase
Most common presentation of Klinefelter syndrome
Infertility
