Disorders Flashcards
Angelman
Severe / profound intellectual disability
‘Happy puppet’ syndrome - happy disposition, paroxysmal laughter, absence of speech, hand flapping, clapping, ataxia, anecdotal love of water and music
86% have epilepsy
Fragile X
X-linked dominant transmission
Common inherited cause of LD, 10-12% of LD in men
Greater in males, ‘protective’ affect of normal X in females
CGG repeats on X chromosome (Xq27.3)
Large head, large ears, elongated face, high arched palate, short stature, mitral valve prolapse, poor muscle tone, large testes, hyperextensible joints
Enlarged ventricles, hippocampus, caudate nucleus + reduced posterior cerebellar vermis
Prada-Willi Syndrome
Microdeletion paternal 15q12
M:F = 4:3, incidence 1:10,000-40,000
Compulsive behaviour, hyperphagia, hoarding, impulsivity, emotional lability, tantrums, excessive daytime sleepiness, skin-picking, aggression
Postnatal factors associated with LD
CNS infections
Intracranial tumours
Hypoxic brain injury
Head injury
Exposure to toxic agents
Psychosocial environment (e.g. deprivation)
Neuropathological changes in Down Syndrome
> 40 changes similar to AD
Reduced brain weight, reduced gyri, cortical thinning, underdeveloped middle lobe of cerebellum, reduced neuronal numbers in cerebellum / locus caeruleus / basal forebrain, reduced cholinergic neurons, epilepsy
Lesch-Nyhan Syndrome
Extremely rare, recessive
Defect on short arm of X chromosome
Deficiency in hypoxanthine phosphoribosyl transferase - build up of uric acid
Severe compulsive self mutilation (lip / cheek / finger biting)
Foetal alcohol syndrome
Microcephaly, short palpebral fissure, small maxillae and mandibles, flat philtrum, thin upper lip, short stature
Mild - mod LD, irritability, innattention, memory impairment
DiGeorge syndrome (velocardiofacial)
Microdeletion of chromosome 22q11.2
1:2000
Intellectual disability (2/3 mild, 1/3 mod), cardiac abnormalities (70%), microcephaly, cleft palate, small mouth, long face, narrow palpebral fissure, minor ear abnormalities), hypocalcaemia (60%), hypospadias, long thin hands, schizophrenia, blunted affect
Cornelia de Lange syndrome
Rare, lack of pregnancy associated plasma protein (PAPPA) linked to chromosome 9q33
Severe / profound intellectual disability, short stature, hypertrichosis, prominent philtrum, small upturned nose, thin down turning upper lip, microcephaly, low set ears, small hands and feet
GI issues, CHD, visual & hearing problems, epilepsy, death in infancy, self-injury, tantrums, stereotypic movements, twirling
Tuberous sclerosis
Autosomal dominant
M:F 1:1
Varying degrees of LD (usually severe)
Klinefelter syndrome
47, XXY
1:1000 live male births
Sparse body hair, hypogonadism, gynaecomastia, tall stature, thin build, median IQ of 90
Uncertain association with psychiatric disorders
Hunter Syndrome
X-linked recessive
1:100,000
Deficiency of iduronate sulfatase (linked to Xq27-28) and consequent accumulation of glycosaminoglycans
Prada-Willi clinical features
Hypotonia, failure to thrive, obesity, small hands & feet, micro-orchidism, cryptorchidism, short stature, almond shaped eyes, fair hair & light skin, flat face, scoliosis, orthopaedic problems, mild-mod LD
Williams syndrome
Hypercalcaemia (50%)
Supraventricular AS
Elfin features
Anxiety + fears
Abnormal attachment behaviour, poor peer relationships, hypersensitivity (or conversely social disinhibition + friendliness)
Verbal skills > visual + motor skills
Phenylketonuria
Autosomal recessive
Severe LD
Deficits in phenylalanine hydroxylase activity - build up of phenylalanine
Rubenstein-Taybi syndrome
Broad thumbs + great toes, persistence of fetal finger pads, short upper lip, pouting lower lip, beaked nose, long eyelashes, cardiac problems, GI problems, epilepsy (25%), sleep problems, stereotypies
Laurence-Moon syndrome
AKA Laurence-Moon-Biedl syndrome which also incorporates Bardet-Biedl syndrome which shares clinical features, but additionally there is cental obesity + polydactyly
Mild-mod LD, short stature, spastic paraparesis, hypogenitalism, night blindness, diabetes, renal problems
Smith-Magenis Syndrome
‘Self-hugging’ posturing, aggression, self-injury, hyperactivity, severe sleep problems, other autistic features
Sanfilippo
Autosomal recessive
Breakdown of heparan sulfate (types A-D)
Severe LD, claw hands, dwarfism, hypertrichosis, hearing loss, hepatosplenomegaly, biconvex lumbar vertebrae, joint stiffness, restlessness, sleep problems, challenging behaviour
Homocystinuria
Lens subluxatoin hallmark - may cause step wise deterioration in visual acuity
Skeletal + connective tissue disorders affect 50% - marfinoid body habitus, arachnodactyly, joint laxicity, osteopaenia, scoliosis, vertebral collapse, LD (not universal, may be subtle), autism, behavioural disturbance
Usher syndrome
Retinitis pigmentosa, congenital deafness, vestibulo-cochlear ataxia, ID (23%), psychosis (usually schizophrenia) in 15%
