General Medicine for the Optometrist (3)

Dr Russell Watkins

GENETIC DISORDERS

Genetic disorders are not rare In a population of 100,000

10 children will be born with a genetic disorder

10 individuals will develop a genetic disorder in later life

10,000 adults will develop diseases with strong genetic components

GENETIC DISORDERS

Genetic disorders may be classified as Cytogenetic (chromosomal) Mendelian Mutlifactorial

GENETIC DISORDERS

Cytogenetic disorders may be due to Alterations in the number of chromosomes

• Monosomy (2n-1)• Trisomy (2n+1)• Mosaicism

Alterations in the structure of chromosomes• Translocation• Deletion etc

GENETIC DISORDERS

Examples Trisomy 21 (Down Syndrome) Other trisomies e.g. 18 (Edward’s syndrome)

& 13 (Patau’s syndrome) are rare Cri du chat syndrome (deletion of short arm of

chromosome 5 [5p-]) Klinefelter’s & Turner’s syndromes (sex

chromosomes)

GENETIC DISORDERS

Trisomy 21 (Down Syndrome) 95% have a complete extra ch21 (47, XY,

+21) Translocations make up ~4% (usually 21q to

22 or 14) Mosaicism ~1%

GENETIC DISORDERS

General features Short stature, flattened bridge of nose Enlarged tongue, short fingers Simian crease, cardiac problems (septal) Recurrent infections, leukaemia Alzheimer’s

GENETIC DISORDERS

Ocular features of trisomy 21 Hypertelorism Epicanthus & mongoloid slant Ectropion Blepharoconjunctivitis Strabismus & nystagmus

GENETIC DISORDERS

Ocular features of trisomy 21 Keratoconus Cataract Brushfield’s spots Hypoplastic disc Refractive errors (esp. myopia)

GENETIC DISORDERS

Types of Mendelian disorders Autosomal dominant Autosomal recessive X-linked dominant X-linked recessive

BASIC GENETICS Autosomal dominant examples are

Neurofibromatosis Myotonic dystrophy Retinitis pigmentosa Marfan’s syndrome

X-linked dominant examples are rare Y-linked diseases are as yet unknown

GENETIC DISORDERS

Autosomal recessive examples are Cystic fibrosis Retinitis pigmentosa

X-linked recessive examples are Retinitis pigmentosa Choroideraemia

GENETIC DISORDERS

Multifactorial inheritance The major contribution by genetic factors to

disease Do not follow simple Mendelian patterns Determined by the summation of effects of

multiple alleles at different loci together with environmental factors

GENETIC DISORDERS

Mitochondrial inheritance Maternal transmission only Mitochondria found in cytoplasm -

sperm have no cytoplasm Important example

• Leber’s optic neuropathy

ENDOCRINE DISEASE Acromegaly

Rare Caused by a benign pituitary adenoma in

almost all cases Males & females affected equally Incidence is highest in middle age One-third present with change in appearance

& one-quarter present with visual field defects or headaches

Thyroid Eye Disease

Thyroid disease Thyroid gland may be under- or overactive A goitre may be present Thyroid function may be normal in the

presence of a goitre Hypothyroidism may be

• Autoimmune (commonest cause)• Iatrogenic (e.G. Surgery)• Nutritional ( iodine)

Thyroid Eye Disease

Patient may be euthyroid, hypothyroid or hyperthyroid

HLA association varies with different populations

Associated with other AI diseases F:M = 4:1; average age of onset 50yrs TED is worse in smokers

Thyroid Eye Disease

Untreated hypothyroidism results in Mental slowness Hypertension Slow movement Deafness Anaemia Et al

Thyroid Eye Disease Hyperthyroidism

Fairly common; F>M; affects 2-5% of all women at some time Most common causes are Graves’ disease (IgG

antibodies bind to the TSH receptor stimulating thyroid hormone production)

Toxic solitary nodule Toxic multinodular goitre

Patients lose weight, are irritable, get diarrhoea & have many other symptoms

Graves’ Disease

Uncertain aetiology - the following are theories T-cells active against antigen common to orbit

& thyroid gland TSH-receptor Ig may activate T- & B-cells T- & B-cells may activate orbital fibroblasts

self-perpetuating inflammation with consequent fibrosis & tethering

Thyroid Eye Disease

The Werner Classification is useful to assess severity of TED - “NO SPECS”

No symptoms or signs Only signs, e.g. lid retraction, lid lag, SLK Soft tissue swelling e.g. lid oedema Proptosis - unilateral or bilateral EOM involvement - usually IR & MR Corneal ulceration Sight loss - corneal ulceration, optic

neuropathy, OHT

Thyroid Eye Disease Lymphocytic infiltrate 8x increase in EOM size Later, there is necrosis & scarring Ophthalmologists may

Consult with colleagues about thyroid disease control Give lubricants for corneal protection Perform tarsorrhaphy Reduce IOP Use steroids, RT or orbital decompression to relieve

pressure on optic nerve

HYPERLIPIDAEMIA

Triglycerides & cholesterol are transported around the bloodstream in lipoprotein particles Chylomicrons VLDLs IDLs LDLs HDLs

HYPERLIPIDAEMIA

Hyperlipidaemia is a major risk factor for atherogenesis

Synergistic with other risk factors (smoking, DM, hypertension)

Most hyperlipidaemic patients are asymptomatic