Clinical Aspects of Learning Disorders

Question 1

About what % of early miscarriages have abnormalities due to genetic disease?

Answer 1

About 50% of 1st trimester miscarriages.

Question 2

About what % of newborn infants have a major congenital abnormality?

Answer 2

2-3%

Question 3

About what % of childhood deafness, blindness and severe mental retardation is caused by genetic disorders?

Answer 3

About 50%

Question 4

About what % of adult chronic disease is caused by genetic abnormalities?

Answer 4

About 10%

Question 5

What is the role of a clinical geneticist?

Answer 5

• Establish a diagnosis -history, examination, investigations
• Risk assessment
• Communication
• Discussion of options
• Counselling of other family members
• Long-term contact and support

Question 6

What referral indications might be received in the genetics clinic?

Answer 6

• Infant deaths, still-births and miscarriages
• Mental/physical handicap
• Congenital abnormalities
• Maternal medical conditions e.g. epilepsy, diabetes/medication
• Neural tube defects
• Family history of known genetic conditions
• Family history of cancer
• Consanguinity

Question 7

How can learning disorders be defined using IQ?

Answer 7

Learning disorders can be defined based on IQ. Typically an IQ less than 70 will be defined as a learning disorder.

Mild = 50-55 to 70
Moderate = 35-40 to 50-55
Severe = 20-25 to 35-40
Profound = less than 20-25

Question 8

Define Mild learning disorder.

Answer 8

Mild = IQ of 50-55 to 70

Question 9

Define Moderate learning disorder.

Answer 9

Moderate = IQ of 35-40 to 50-55

Question 10

Define Severe learning disorder.

Answer 10

Severe = IQ 20-25 to 35-40

Question 11

Define Profound learning disorder.

Answer 11

Profound = IQ less than 20-25

Question 12

Other than based on IQ scores, how can learning disorders be defined?

Answer 12

Learning disorders can also be defined on a functional basis. This is based on dysfunction or impairment in more than 2 areas of communication, self-care, home living, social/interpersonal skills, use of community resources, self direction, functional academic skills, work, leisure, health and safety.

Question 13

What are the most common causes of mild mental retardation?

Answer 13

Down syndrome, Fragile X and other chromosomal abnormalities.

Question 14

What are the most common causes of severe mental retardation?

Answer 14

Chromosomal abnormalities (including Down), Fragile X, CNS, environmental/prematurity, malformation/syndrome, unknown

Question 15

What is clinical dysmorphology?

Answer 15

A branch of clinical genetics concerned with the diagnosis and the interpretation of structural defects. There are 3 main types of structural defects known as deformations, disruptions and malformations.

Question 16

What are the 3 main types of structural defects in clinical dysmorphology?

Answer 16

There are 3 main types of structural defects known as deformations, disruptions and malformations.

Question 17

What is a deformation in terms of dysmorphology?

Answer 17

A deformation is caused by a mechanical force such as excessive moulding. This often resolves when the mechanical force is removed.

Question 18

What is a disruption in terms of dysmorphology?

Answer 18

A disruption is the breakdown of normal development such as amniotic bands which restrict the supply of blood to the digits and result in amputation.

Question 19

What is a malformation in terms of dysmorphology?

Answer 19

A malformation is an intrinsic developmental defect. E.g. cleft lip and palate.

Question 20

What does the word syndrome mean?

Answer 20

A greek word meaning ‘things that run together’.

Question 21

What is the definition of a syndrome?

Answer 21

A syndrome can be defined as a non-random association of multiple malformations or alterations in body form that are pathogenetically related. Over 4000 syndromes listed on the Winter-Baraitser Dysmorphology Database.

Question 22

Why does it help to make a diagnosis if they have a syndrome?

Answer 22

• For parents it helps to have a name for a condition in order to explain to others what is wrong, to answer whether or not an individual has been responsible for the condition (or passed it on to their offspring) and also to get extra help.
• Once the condition is known we can give information regarding the associated problems, prognosis, inheritance and treatments. In addition, once you have a diagnosis it is often that you do not require further investigations to come up with a further diagnosis.

Question 23

Describe what occurs in a dysmorphology consultation.

Answer 23

• First look at history including the pregnancy, birth, development and medical problems.
• Look at the family history to see if there are other individuals involved with the same condition in the family and if there is any consanguinity.
• Physical examination.
• Examine parents and siblings if necessary. Some features may be familial.
• Also important if you are seeing older children or adults to try and review some younger photos as it is possible in some conditions that the characteristic appearances are only present at certain ages.

Question 24

What is meant by diagnosis by Gestalt?

Answer 24

This is diagnosis by immediate pattern recognition.

Question 25

What anatomical landmarks in the face can we use to define dysmorphology?

Answer 25

- Facial asymmetry - Coarse facial features - Mid-face hypoplasia (excluding malar region)

Question 26

What anatomical landmarks of the ear can we use to define dysmorphology?

Answer 26

- Ear tags - Skin pits - Absence of lobes - lop ears - crumpled ears

Question 27

What anatomical landmarks of the eyes can we use to define dysmorphology?

Answer 27

- Spacing of the eyes (hypo or hyper telorism) - Sloping of the eyes - Epicanthic folds - Coliboma (defect in the iris)

Question 28

What anatomical landmarks of the eyes can we use to define dysmorphology?

Answer 28

- can describe the anatomy including bridge, tip, nostril and nasal septum etc. and can describe abnormalities of these.

Question 29

What anatomical landmarks around the mouth can we use to define dysmorphology?

Answer 29

- philtrum features - Upper lip e.g. thin upper lip and smooth philtrum seen in fetal alcohol syndrome.

Question 30

What disorders of skin pigmentation may be seen?

Answer 30

- Hyperpigmentation

Question 31

How can we define pathologies based on height?

Answer 31

We first look at whether the short stature is normal or abnormal. If it is abnormal then we will look to see if it is pathologic. If it is pathologic then we need to define whether it is proportionate or disproportionate. If it is an abnormality of the skeleton which is usually disproportionate it is known as skeletal dysplasia. For example, individuals may have short limbs or a short trunk.

Question 32

Describe what kind of limb shortening may be seen in skeletal dysplasia.

Answer 32

- Shortening of the proximal limb is known as Rhizomelia. | - Shortening of the distal limb is known as Mesomelia.

Question 33

What is Rhizomelia?

Answer 33

Shortening of the proximal limb in skeletal dysplasia is known as Rhizomelia.

Question 34

What is Mesomelia?

Answer 34

Shortening of the distal limb in skeletal dysplasia is known as Mesomelia.

Question 35

What is Acromelia?

Answer 35

Shortening of the digits in skeletal dysplasia is known as Acromelia.

Question 36

What is polydactyly?

Answer 36

Extra digits

Question 37

What is syndactyly?

Answer 37

conjoined digits

Question 38

What is clinodactyly?

Answer 38

In curving of the little finger

Question 39

What is talipes?

Answer 39

Talipes is a condition that can affect one or both of a baby's feet from birth. In most cases, the front half of the foot turns inwards and downwards. This is called congenital talipes equinovarus (CTE). It is also known as club foot.

Question 40

How do we decide a child is dysmorphic?

Answer 40

Everybody is dysmorphic. Subtle dysmorphic features in themselves don't make a diagnosis, it is the combination of these plus other clues in history. Deciding a child is dysmorphic or not can be difficult (remember to look at parents). Sometimes a parent has the the syndrome.

Question 41

Describe the features of Kabuki Syndrome.

Answer 41

- Developmental delay - Long palpebral fissures - Everted lateral lower lid - Arched eyebrows with sparse lateral 1/3 - Broad nasal tip - Large ears, prominent ear lobes - High palate - Lip pits - Fetal finger pads - Short stature - Premature thelarche (breast development) - CHD, renal anomalies

Question 42

What gene mutation is responsible for Sotos syndrome?

Answer 42

NSD1 gene mutation.

Question 43

What are the issues with correctly diagnosing syndromes in individuals?

Answer 43

- Syndromes can be extremely variable. - syndromes may be very rare and possibly unique to a patient or family. - One syndrome can be caused by different genes (heterogeneity). - One gene can be the cause of a number of different syndromes. - Additional features can develop with time, follow up may be needed to make diagnosis. - Genetic tests have limitations.

Question 44

Why is the identification of dysmorphology important?

Answer 44

- Dysmorphology is important for diagnosis and genetic counselling. - It is important for research in the identification of different syndromes, identification of genes and chromosomal regions responsible for specific syndromes, and the understanding of specific mechanisms and gene pathways.

Question 45

What resources may be utilised by the clinical genetics department in order to define dysmorphology and classify syndromes?

Answer 45

- Karyotyping, FISH, telomeres, skin biopsy, DNA testing, CGH microarrays etc. - Clinical photos - Radiology - Other opinions e.g. opthalmology, dental, cardiac - Databases e.g. Winter-Baraitser - Books, journals, Pubmed, OMIM - Discussion with colleagues - Dysmorphology meetings (national/international) - Fetal pathology meetings

Question 46

List some of the genetic databases available to aid diagnosis.

Answer 46

- BSHG - OMIM - GeneTests - The Winter-Baraitser Dysmorphology Database - European Directory of DNA Laboratories

Question 47

What are the features of a syndrome often termed?

Answer 47

Handles

Question 48

List common syndromic handles from those found in fewest syndromes to those found in most syndromes.

Answer 48

1) . 4/5 syndactyly of hands 2) . Single central incisor 3) . Radial aplasia 4) . Preaxial polydactyly 5) . Anal atresia 6) . Exomphalos 7) . Cleft lip 8) . Micrognathia 9) . Preauricular skin tags/pits 10) . Single palmar crease 11) . Low set ears 12) . Hypertelorism