Genetics and Dysmorphology Flashcards by Ailsa Morris

What are the typical facial features of Down Syndrome?

Round face with flat nasal bridge and short neck
Upslanted palpebral fissures
Epicanthic folds
Brushfield spots in iris
Small mouth with protruding tongue
Small ears
Flat occiput and 3rd fontanelle

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What are the limb features of Down syndrome?

Single palmar creases
Incurved and short 5th fingers
Wide “sandal-toe” gap between 1st and 2nd toes

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What are the neurological features of Down syndrome?

Hypotonia

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What percentage of children with Down syndrome have a congenital heart defect?

30-40%

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What are the long term or later medical issues in Down syndrome?

DD
LD
Short stature
Increased susceptibility to infection
Hearing or visual impairments
Increased risk of hypothyroidism (<15%)
Increased risk of leukaemia and solid tumours (<1%)
Increased risk coeliac disease
OSA
Epilepsy
Early-onset Alzheimers

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What types of congenital heart defects are most common with Down syndrome?

ASD and AVSD

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What are the 3 types of genetic cause for Down syndrome?

Meiotic nondisjunction (94%)
Translocation (5%)
Mosaicism (1%)

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What are the presenting features of Edwards syndrome?

LBW
Prominent occiput
Small mouth and chin
Short sternum
Flexed, overlapping fingers
“rocker-bottom” feet
Cardiac and renal malformations

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What gut features can present in Down syndrome?

Duodenal atresia
Hirschsprung’s (<1%)

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How is Down syndrome diagnosed?

Clinical suspicion
rtPCR or FISH

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What are the clinical features of Turner syndrome?

Lymphoedema of hands and feet in the neonate
Spoon shaped nails
Short stature
Neck webbing or thick neck
Wide carrying angle
Widely spaced nipples
Delayed puberty
Infertility
Hypothyroid risk
Renal anomalies common
Pigmented moles
Recurrent OM
Congenital heart defects

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What is trisomy 18 better known as?

Edwards syndrome

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What is trisomy 13 better known as?

Patau syndrome

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What are the presenting features of Patau syndrome?

Structural defect of the brain
Scalp defects
Small eyes
Cleft lip and palate#
Polydactyly
Cardiac and renal malformations

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What is the most common congenital heart defect in Turner syndrome?

Coarctation of the aorta

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What syndrome is best characterised by the karyotype XO?

Turner syndrome

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What is the treatment offered in Turner syndrome?

Growth hormone
Oestrogen replacement to develop secondary sexual characteristics

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How is intellect affected in Turner syndrome?

It is often unaffected

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Which condition is caused by the 5p microdeletion?

Cri-du-Chat syndrome

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What are the clinical features of Klinefelter syndrome?

Infertility (most common presentation)
Hypogonadism and small testes
Gynaecomastia in adolescence
Tall stature

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What are the presenting features in Cri du chat syndrome?

High pitched cry in infancy
Hypotonia
Microcephaly
Intellectual disability

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What is best described by the karyotype XXY?

Klinefelter syndrome

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Which condition is caused by the 22q11.2 microdeletion?

DiGeorge syndrome

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How does Williams syndrome present?

Characteristic facies
Transient neonatal hypoglycaemia
Supravalvular aortic stenosis
Mild-mod LD
Short stature

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What are the typical features of DiGeorge syndrome?

CATCH Cardiac abnormality (interrupted aortic arch, truncus arteriosus, TOF) Abnormal facies Thymic aplasia Cleft palate Hypocalcaemia/hypoparathyroidism Intellectual disability Autism/ADHD

Which syndrome is caused by a 7q11 microdeletion?

Williams syndrome

By which form of inheritance is achondroplasia inherited?

By which form of inheritance is familial hypercholesterolaemia (almost always) inherited?

By which form of inheritance is Huntington disease inherited?

By which form of inheritance is Marfan syndrome inherited?

By which form of inheritance is Osteogenesis imperfecta (most forms) inherited?

By which form of inheritance is Neurofibromatosis inherited?

By which form of inheritance is Noonan syndrome inherited?

By which form of inheritance is Tuberous sclerosis inherited?

By which form of inheritance is Otosclerosis inherited?

By which form of inheritance is Polyposis coli inherited?

By which form of inheritance is CAH inherited?

By which form of inheritance is achondroplasia inherited?

By which form of inheritance is CF inherited?

By which form of inheritance is Friedreich Ataxia inherited?

By which form of inheritance is Galactosaemia inherited?

By which form of inheritance is Glygogen storage diseases inherited?

By which form of inheritance is Hurler syndrome inherited?

By which form of inheritance is Oculocutaneous albinism inherited?

By which form of inheritance is PKU inherited?

By which form of inheritance is Sickle cell inherited?

By which form of inheritance is Thalassaemia inherited?

By which form of inheritance is Tay-Sachs disease inherited?

By which form of inheritance is SMA1 inherited?

By which form of inheritance is Red-Green colour-blindness inherited?

X-linked recessive

Which gene is implicated in fragile X syndrome?

FMR1 gene

By which form of inheritance is Fragile X syndrome inherited?

X-linked recessive

By which form of inheritance is Haemophilia A and B inherited?

X-linked recessive

By which form of inheritance is DMD inherited?

X-linked recessive

By which form of inheritance is G6PD deficiency inherited?

X-linked recessive

By which form of inheritance is Hunter syndrome inherited?

X-linked recessive

In an x-linked recessive condition what is the chance that a daughter of a female carrier will carry the condition?

1 in 2

What abnormalities are considered in VACTERL association?

Vertebral anomalies Anal atresia Cardiac defects TracheoEsophageal fistula Renal anomalies Limb defects

By which form of inheritance is hypophosphataemic rickets inherited?

X-linked dominant

What conditions involve trinucleotide repeat expansion mutations?

Fragile X Myotonic dystrophy Huntington's disease

In an x-linked recessive condition what is the chance that a son of a female carrier will have the condition?

1 in 2

In an x-linked recessive condition what is the chance that a daughter of an affected male will carry the condition?

100%

Are males or females primarily affected in X-linked dominant conditions?

Both, usually males will have a more severe phenotype

In an x-linked recessive condition what is the chance that a son of an affected male will have the condition?

What is meant by the imprinting and uniparental disomy phenomenon?

Expression of genes dependent on parental sex that transmitted the gene

Which condition will occur if a child receives no paternal functional copy of chromosome 15?

Prader-Willi Syndrome

What are the clinical features of fragile X syndrome?

Mod-sev LD Macrocephaly Marcoorchidism Characteristic facies (long face, large everted ears, prominent mandible, broad forehead) Mitral valve prolapse Joint laxity Scoliosis Autism Hyperactivity

Which condition will occur if a child receives no maternal functional copy of chromosome 15?

Angelman syndrome

What are the characteristic features of PWS?

Characteristic facies Hypotonia at birth Hypogonadism Neonatal feeding difficulties Faltering growth in infancy Hyperphagia and obesity inadulthood DD and LD

What are the clinical features of Angelman syndrome?

Severe cognitive impairment Characteristic facial appearance Ataxia Epilepsy

What are the clinical features of Noonan syndrome?

Characteristic facies Short, webbed neck with trident hair line Pectus excavatum CHD (pulmonary stenosis and ASD) Short stature Occasional mild LD

How are porphyrias inherited?

Typically AD but can be AR

How is CAH inherited?

In CAH, when should biological sex be assigned?

When karyotype available

What chromosomal abnormality is associated with PWS?

Deletion of the long arm on paternal chromosome 15 or maternal uniparental disomy

How is haemophilia A inherited?

X-linked recessive

Which gene is associated with achondroplasia?

FGFR3 gene

Which gene is associated with Rett syndrome?

MECP2

What are the features of Pallister-Killian syndrome?

Bitemporal sparsity of hair Severe DD Epilepsy Hypotonia Abnormal skin pigmentation

What chromosomal abnormality is associated with Pallister-Killian syndrome?

Mosaicism for an isochromosome comprising the short arms for Ch12

What is the embryological failure than leads to Treacher-Collin's syndrome?

Underdevelopment of first pharyngeal arch

How is NF1 typically inherited?

What are the features of Treacher-Collins syndrome?

Underdeveloped facial bones Micrognathia Downward-slanting eyes

What is the typical inheritance pattern in Kearns-Sayre syndrome?

Sporadic cases

What are the typical symptoms associated with Kearns-Sayre syndrome?

Pigmentary retinopathy Progressive external ophthalmoplegia Heart block Ataxia +/- elevated CSF protein

What is formed as the penultimate step before haem formation?

Protoporphyrin

What ophthalmological features are seen in tuberous sclerosis?

Harmatomas or retinal hypopigmented patches

How does Bardet-Biedl syndrome present?

Obesity Hypogonadism Retinal degeneration Polydactyly Cardiac defects Renal anomalies T2DM Anosmia

How is Bardet-Biedl syndrome inherited?

What are the features of branchio-oto-renal syndrome?

Ear pits Hearing loss Renal abnormalities (dysplastic kidneys or aplasia)

What is the inheritance of branchio-oto-renal syndrome?

AD - variable penetrance

What chromosome is involved in branchio-oto-renal syndrome?

Chromosome 8 (most commonly)

What chromosomal abnormality is associated with Cr-du-chat syndrome?

5p deletion

What are the typical features of Lesch-Nyhan syndrome?

Overproduction of uric acid - gout and kidney stones Neurological dysfunction Self-mutilating behaviours - such as lip and finger biting

How does Fanconi anaemia present?

Radial ray abnormalities (e.g. absent thumbs) SGA Pancytopenia

How is Fanconi anaemia diagnosed?

Chromosome breakage studies

How is Fanconi anaemia inherited?

How is Cowden disease inherited?

How does FISH work?

Fluorescent dye is attached to chromosomal probes, which then attach to the target DNA to locate each section of the chromosomes

What are the features of Simpson-Golabi-Behmel syndrome in males?

Macrocephaly Coarse facial features Down-slanting palpebral fissures DD

What are the features of Cowden disease?

Multiple hamartomas Increased risk malignancies incl. thyroid and endometrial Macrocephaly Developmental delay

What are the features of mosaic trisomy 8?

Deep-set eyes Everted lower lip Deep palmar and plantar creases Micrognathia Elongated skull Upturned nose

What is the inheritance pattern of Simpson-Golabi-Behmel syndrome?

X-linked recessive

How is Jeune syndrome inherited?

What are the features of Simpson-Golabi-Behmel syndrome in females?

Subtle facial manifestations - large mouth and pointed chin Sometimes a coccygeal appendage

How does Jeune syndrome present?

Lung hypoplasia Poor cartilage development Short thorax and small ribs and limbs Renal abnormalities - cystic kidneys

What mutated gene causes Simpson-Golabi-Behmel syndrome?

GPC3 gene

What is Southern blotting technique?

Demonstration of the presence or absence of specific DNA fragments in a mixture of DNA

What is the unstable trinucleotide repeat in fragile X syndrome?

CGG

In what condition are brushfield spots commonly seen?

T21

What are the features of Beckwith-Wiedemann syndrome?

Large tongue Hepatomegaly LGA Umbilical hernia Macroglossia Macrosomia Hemi-hyperplasia Organomegaly Cleft palate

What are the features of Angelman syndrome?

DD Lack of speech Walking and balance disorders Happy demeanor Jerky movements

What are the features of Pendred syndrome?

Severe, profound bilateral SN deafness Vestibular dysfunction Goitre Bilateral dilated vestibular aqueducts

How is Pendred inherited?

What are the features of Sotos syndrome?

Macrocephaly Prominent forehead Down-slanting palpebral fissures Prominent jaw High and narrow palate Can be assoc. with ventricular dilatation and seizures

What genetic mutation causes Sotos syndrome?

NSD1 gene mutations or deletions affecting 5q35 locus Most are de novo

How does Tay-Sachs present?

Cherry red spot on ophthalmological exam Affects central and peripheral nervous system