GENETIC DISORDERS AND CONGENITAL SYNDROMES Flashcards
What term best describes the inheritance pattern of Marfan’s syndrome?
Autosomal dominant
What term best describes the inheritance pattern of sickle cell disease?
Autosomal recessive
What term best describes the inheritance pattern of thalassaemia?
Autosomal recessive
What term best describes the inheritance pattern of Haemophilia A and B?
X-linked recessive
What term best describes the inheritance pattern of neurofibromatosis type 1?
Autosomal dominant
What term best describes the inheritance pattern of colour blindness?
X-linked recessive
What term best describes the inheritance pattern of Duchenne muscular dystrophy?
X-linked recessive
What term best describes the inheritance pattern of myotonic dystrophy?
Autosomal dominant
What term best describes the inheritance pattern of phenylketonuria?
Autosomal recessive
What term best describes the inheritance pattern of congenital adrenal hyperplasia?
Autosomal recessive
What term best describes the inheritance pattern of tuberous sclerosis?
Autosomal dominant
What term best describes the inheritance pattern of Fragile X syndrome?
X-linked recessive
What term best describes the inheritance pattern of cystic fibrosis?
Autosomal recessive
What term best describes the inheritance pattern of G6PD?
X-linked recessive
What term best describes the inheritance pattern of achondroplasia?
Autosomal dominant
What is the most common genetic cause of severe learning difficulties?
Fragile X syndrome
What is the mutation in Fragile X syndrome?
Expansion of a triplet repeat in the FRAXA gene
What are the clinical features of Fragile X syndrome?
Learning difficulties
Macrocephaly
Long face
Large ears
Macro-orchidism (large testes)
Taller than average
What is the other name for trisomy 13?
Patau syndrome
What are the features of Patau syndrome (trisomy 13)?
Microcephalic, small eyes
Cleft lip/palate
Polydactyly
Scalp lesions
What is the other name for trisomy 18?
Edwards syndrome
What are the features of Edwards syndrome (trisomy 18)?
Micrognathia - undersized jaw
Low-set ears
Rocker bottom feet
Overlapping of fingers
What is the other name for trisomy 21?
Down syndrome
What are the dysmorphic facial features of Down syndrome?
Round face
Epicanthic folds
Flat nasal bridge
Protruding tongue
Small ears
Brushfield spots on iris
What are the non-facial dysmorphic features of Down syndrome?
Single palmar crease
Flat occiput
Incurved little fingers
Gap between first and second toes
Small stature
What are the structural defects associated with Down syndrome?
Cardiac defects (VSDs)
Duodenal atresia (remember double bubble sign on x-ray)
What are the neurological features of Down syndrome?
Hypotonia
Developmental delay
Mean IQ of 50
What are the late medical complications of Down syndrome?
Increased risk of leukaemia
Respiratory infections
Hypothyroidism
Alzheimer’s disease
Atlantoaxial instability
Coeliac disease
What is the chromosomal defect that causes Turner syndrome?
45 XO - only 1 X chromosome
Is maternal age related to Turner syndrome, Down syndrome and Patau syndrome?
No. Age is not related to Turner syndrome. It is a risk factor for the other two.
What are the dysmorphic features of Turner syndrome?
Lymphoedema of the hands and feet at birth
Neck webbing
Widely spaced nipples
Wide carrying angle (cubitus valgus)
Short stature
What are the structural and functional abnormalities associated with Turner syndrome?
Gonadal dysgenesis - streak ovaries
Congenital heart disease, particularly coarctation of the aorta
Renal abnormalities
Specific learning difficulties - visuo-spatial
What therapies can be offered to people with Turner syndrome?
Growth hormone improves final height
Oestrogen therapy is given at 11 to produce maturation of secondary sexual characteristics including breast development
Towards the end of puberty, progestogen is added to maintain uterine health and allow monthly withdrawal bleeds
IVF will usually be needed to achieve pregnancy although natural pregnancy can occur
What is the chromosomal abnormality that causes Klinefelter syndrome?
47 XXY
What are the clinical features of Klinefelter syndrome?
Tall stature with long legs
Small testes
Gynaecomastia
Learning difficulties
What treatment might be needed for someone with Klinefelter syndrome?
Testosterone to stimulate development of secondary sexual characteristics
What are the features of Noonan syndrome?
Referred to as the male version of Turner syndrome:
Webbed neck
Pectus excavatum
Short stature
Pulmonary stenosis
What are the features of Pierre-Robin syndrome?
Very similar to Treacher Collins syndrome:
Micrognathia
Posterior displacement of the tongue (may result in upper airway obstruction)
Cleft palate
What are the features of Prader Willi syndrome?
Hypotonia
Hypogonadism
Obesity
Inherited through imprinting (does not inherit gene from father)
What are the features of William’s syndrome?
Short stature
Learning difficulties
Friendly, extrovert personality
Transient neonatal hypercalcaemia
Supravalvular aortic stenosis
What are the features of fetal alcohol syndrome?
Saddle-shaped nose
Maxillary hypoplasia
Absent philtrum between the nose and upper lip
Short, thin upper lip
Development delay
Cardiac defects - particularly ASD
What are the features of baby born to opiate users?
Evidence of drug withdrawal:
Jitterness
Sneezing
Yawning
Poor feeding
Vomiting
Diarrhoea
Weight loss
Seizures
A 14-year-old boy is brought in by his mother who noticed her child had repeated episodes of slurred speech and gait abnormalities. On musculoskeletal examination, you notice muscle weakness, dysdiadochokinesis and spinal scoliosis. What is the mode of inheritance of this condition?
X-linked recessive
Autosomal dominant
Point mutation
X-linked dominant
Autosomal recessive
Autosomal recessive - This is Friedrich’s ataxia
What are the features of Friedrich’s ataxia?
Bilateral spastic paresis
Bilateral loss of proprioception (dysdiadochokinesis) and vibration sensation
Bilateral limb ataxia
Scoliosis
What are the spinal tracts affected by Friedrich’s ataxia?
Lateral corticospinal tracts
Dorsal columns
Spinocerebellar tracts
Autosomal recessive conditions are often thought to be ‘metabolic’ as opposed to autosomal dominant conditions being ‘structural’. What are the metabolic conditions that do not follow this rule?
Hunter’s and G6PD are X-linked recessive
Hyperlipidemia type II and hypokalemic periodic paralysis are autosomal dominant
Autosomal recessive conditions are often thought to be ‘metabolic’ as opposed to autosomal dominant conditions being ‘structural’. What are the structural conditions that do not follow this rule?
Ataxia telangiectasia and Friedreich’s ataxia are autosomal recessive
A 14-year-old male being investigated for iron-deficiency anaemia is found to have numerous polyps in his jejunum. On examination he is also noted to have pigmented lesions on his palms and soles. What is the likely diagnosis?
Hereditary non-polyposis colorectal carcinoma
Gardner’s syndrome
Familial adenomatous polyposis
Peutz-Jeghers syndrome
Hereditary haemorrhagic telangiectasia
Peutz-Jeghers syndrome
What are the clinical features of Peutz-Jeghers syndrome?
Hamartomatous polyps in GI tract (mainly small bowel)
Pigmented lesions on lips, oral mucosa, face, palms and soles
Intestinal obstruction e.g. intussusception
Gastrointestinal bleeding
What is the inheritance pattern of Peutz-Jeghers syndrome?
Autosomal dominant
What is the prognosis of someone with Peutz-Jeghers syndrome?
Around 50% of patients will have died from a gastrointestinal tract cancer by the age of 60 years.
