Condition AZ: i

Information and support in the UK for metabolic diseases is provided by Metabolic Support UK (see entry Inherited Metabolic diseases)

There are two main types of idic (15). Type 1 has the more obvious features and usually contains two extra copies of the so-called Prader-Willi-Angelman critical region (PWACR) on chromosome 15. This region may be deleted in patients with Prader-Willi or Angelman syndrome. Except in very rare circumstances, people with idic (15) do not have Prader-Willi or Angelman syndrome. It is the presence of this extra genetic material that is thought to account for the symptoms seen in individuals with this disorder. Those with type 2 do not have extra copies of the PWACR. Type 2 is not usually associated with any problems but, unlike type 1, it is often passed down through a family.

The features associated with type 1 idic (15) are ‘non-specific’; in other words, they tend not to form an easily recognisable syndrome (pattern), and they are seen in a range of other disorders. The most common features are:

• hypotonia (reduced muscle tone). This is often present at birth but usually decreases with age. Babies may appear ‘floppy’ and have difficulty sucking. Motor milestones (rolling over, sitting up and walking) may be delayed, but most individuals are able to walk independently
• seizures (see entry Epilepsy). Many, but not all, affected children and adults have seizures at some point in their lives. These may be occasional or frequent, short or prolonged
• developmental delay (see entry Learning Disability). Learning difficulties vary in severity but are often moderate to severe.

Autistic behaviours (see entry Autism Spectrum conditions) are also associated with idic (15), including hand flapping, poor eye contact, repetitive or poorly developed speech and a need for ‘sameness’ in environment or daily routine. Many share similar facial characteristics including a flattened nasal bridge giving a ‘button’ nose, skin folds, called ‘epicanthi’ at the inner corners of the eyes, downward slanting eyes and full lips.

Individuals with idic (15) have an extra chromosome made up of some material from the 15th pair of chromosomes. This means that there are forty-seven chromosomes (or occasionally forty-eight or forty-nine) in these cells rather than 46. The extra piece of chromosome 15 has been duplicated end-to-end like a mirror image and is referred to as an ‘isodicentric 15’, an ‘inverted duplication 15’, or a ‘supernumerary marker.’

Distinguishing between the two types of idic (15) is important. Most laboratories now use a technique called array comparative genomic hybridization (aCGH) as the front line test (replacing the karyotype) in patients presenting with the clinical features associated with idic (15). This test will show how much extra chromosome material is present and so distinguish between the two types. FISH (fluorescent in situ hybridisation) follow up studies will still be essential to accurately diagnose idic (15) chromosomes when an imbalance is detected by aCGH.

Treatment is tailored to the individual, and will be based on the features displayed.

Inheritance patterns
Type 1 idic (15) almost always occurs sporadically. In other words, no other family member, brother or sister, is usually affected. However, type 2 idic (15) can be inherited. Genetic advice and counselling should be sought.

Prenatal diagnosis
This is rarely carried out specifically to look for idic (15); however, the diagnosis may be made for the first time by examination of chorionic villus samples (CVS) or amniotic fluid taken for Down syndrome screening. If the idic (15) anomaly is identified, expert advice should be sought.

Information and support in the UK for isodicentric 15 is provided by Unique (see entry Chromosome Disorders).

Individuals with IBS have frequent attacks of abdominal pain or bloating, which are associated with disturbances in defecation (voiding of waste matter or faeces from the bowel), which might be either constipation, diarrhoea or a combination of the two.  In addition to bowel symptoms, sufferers also frequently complain of a variety of other symptoms, especially fatigue, breathlessness, headaches, indigestion, backache, anxiety and depression. Symptoms are commonly brought on by life changes and difficult life situations, but they may also be triggered by food.

IBS can be triggered by an attack of gastroenteritis (especially if this occurs with anxiety and depression), a traumatic event or situation or administration of large or frequent doses of antibiotics.

Studies have shown enhanced gastrointestinal motility and sensitivity, enhanced immune responses, a leaky gut, changes in the composition of bacteria in the large bowel and alterations in the interaction between the brain and gut, but such changes often occur together and may represent a resetting of brain gut function. This can make people with IBS very sensitive to certain foods, especially fats, coffee, wheat, milk, fruits, vegetables and cereal fibre.

There is no specific test for IBS. It is diagnosed by a combination of typical abdominal and bowel symptoms, and the absence of any indications of other chronic abdominal diseases (evacuation of blood or mucus, fever, weight loss, anaemia). In particular, Coeliac Disease and inflammatory bowel disease need to be excluded by tests on samples of blood or faeces. In children, allergies also need to be excluded. 

Symptoms may be eased with antispasmodics, such as Colofac and Spasmonal, and with bowel regulators, such as Imodium and Fybogel. Dietary restriction of fruits and vegetables can alleviate pain bloating, restriction of milk and other dairy products may reduce diarrhoea and reducing intake of fat and coffee can help to prevent abdominal pain. Identification and management of stressful situations can be very helpful in reducing symptoms. Psychological therapies, hypnotherapy and complementary therapy may be helpful when other measures fail.

IBS can tend to run in families, but there is no specific combination of genes for IBS. The association is more likely to be that families share the same diet, experience the same stress and harbour the same bacteria in the colon.

The IBS Network

Tel: 0114 272 32 53
Email: info@theibsnetwork.org
Website: theibsnetwork.org

The IBS Network is the national charity registered in England and Wales no. 1173208 supporting people living with Irritable Bowel Syndrome. Our mission is to provide information, advice and support for people living with IBS and those who care for them and to work alongside health care professionals to facilitate self-care.  

Group details last updated October 2017.

Metabolic Support UK (Formerly CLIMB)

Helpline: 0845 241 2173
Email: via website
Website: metabolicsupportuk.org

The Organisation is a Registered Charity in England and Wales No. 1089588. It offers information and support on metabolic diseases to young people, adults, families and professionals. The Organisation also funds educational and primary research programmes and investigates treatments and medical services.

Group details last reviewed December 2023.

Features on the skin include:

• in the first months of life, skin redness with lines of blisters affect all areas except the face
• as the blisters heal, warty areas occur on the skin of the hands and feet. These usually clear by six months of age
• excessive brown pigmentation occurs in streaks on the body. These fade in adolescence. These give IP its name
• in adulthood pale hairless streaks or patches appear.

Other features include:

• missing, small or misshapen teeth
• alopecia (baldness) or coarse, dull hair
• nail ridging or pitting.

The eyes are often mildly affected. A third of people with IP have a squint. Around 40 per cent have abnormalities of the blood vessels at the back of the eye (retina). Rarely this can lead to retinal scarring and detachment which may cause vision loss, usually in one eye. Screening is advised to avoid this.

Occasionally, seizures (see entry Epilepsy) and learning disability occur. People with IP live as long as people without the condition.

IP is caused by mutations in the NEMO gene on the X chromosome.

• A doctor may observe features of IP.

• A skin biopsy (removal of a small skin sample) can confirm the diagnosis of IP but is not often needed.
• A genetic test, (DNA test), looking for mutations in the NEMO gene, can confirm the diagnosis in most people.
• Testing can also identify family members who carry the genetic mutation causing IP, but are not affected by the condition.

There is no cure for IP.

Management aims to prevent or treat infection of blisters by locally applied medications. This doesn’t shorten the period in which blisters occur. Pigmented (darkly coloured) areas can be camouflaged with creams or cosmetics. A wig may be necessary in rare cases.

An eye examination should be performed soon after birth. IP patients should be reviewed regularly by an ophthalmologist (eye doctor), aiming to prevent eye complications or treat them early to avoid visual problems. Any changes in vision must be reported quickly.

A dentist should check the child’s teeth regularly and specialist referral made if necessary.

Inheritance patterns
X-linked dominant.

Prenatal diagnosis
Genetic counselling is recommended. Prenatal testing is available for families already known to be affected.

Information and support in the UK for incontinentia pigmenti is provided by the Ectodermal Dysplasia Society (see entry Ectodermal Dysplasia).

ITP is usually suspected because of the occurrence of abnormal bruising, small pin-point bleeds into the skin, and occasionally nosebleeds or other abnormal blood loss. It often follows a viral infection.

In ITP, platelets are removed by the body’s immune system as they are inappropriately regarded as ‘foreign’. ITP is thus a type of autoimmune disorder, meaning that the body is inappropriately attacking itself rather than foreign bodies, such as bacteria and viruses.

Mostly we do not know what triggers patients to get ITP. It may occur after infections such as measles, mumps, rubella or chicken pox. Research has also suggested an association between the measles, mumps and rubella (MMR) vaccination and ITP in young children although these episodes appear to be very rare and are mild and acute (short-lasting) with no children going on to develop serious permanent complications.

The diagnosis of ITP involves excluding other things that can cause a low platelet count. For example, some viruses, some drugs and some other haematology conditions can result in a low platelet count and bleeding.

In about 90 per cent of children, ITP is a trivial and rapidly self-correcting condition (acute ITP). The risk of serious bleeding in childhood ITP is very small and, usually, no treatment is necessary other than avoidance of aspirin or ibuprofen – these are part of a class of drugs called non-steroidal anti-inflammatory drugs (NSAIDs), which stop the platelets from working and further increase the risk of bleeding.

Treatment, if required, is aimed at suppressing the immune system to stop the inappropriate destruction of platelets, so reducing the risk of serious bleeding. This is usually achieved by either a short course of steroid drugs, which suppress the immune system, or injection of large amounts of intravenous immunoglobulin (a human, soluble antibody protein), which interfere with the destruction of platelets by the immune system.

In a few children, ITP runs a more prolonged course (chronic ITP). These children will usually be investigated further, including having a bone marrow test. They are also more likely to require treatment. A few children have persistent or chronic and troublesome ITP associated with bleeding. These patients should be referred to a haematology centre with experience in managing children with ITP.

There are a number of new treatments available for people who have persistent or chronic ITP:

• rituximab is a monoclonal antibody. It destroys B cells, which produce the antibodies that destroy the platelets. Good responses have been seen in children with ITP
• romiplostin and eltrombopag are licensed for use in adults and children with chronic ITP both in Europe and in the USA and have shown very good results, with an increase in the platelet count in most people, without many side effects. These drugs work in a different way, by stimulating the bone marrow to produce more platelets rather than suppressing the immune system. They need careful monitoring because the counts can fluctuate quite a lot. These should only be prescribed by a specialist centre where doctors have experience in how to use them.
• Immunosuppression with azathioprine or MMF can be used in patients not responsive to initial treatments
• Rarely children may need to have a splenectomy (this is where the platelets are destroyed). It is not common to take the spleen out for children with ITP now, because of other options. This should only be considered in a specialist centre.

Inheritance patterns
None.

Prenatal diagnosis
Not applicable.

The ITP Support Association

Email: info@itpsupport.org.uk
Website: itpsupport.org.uk

The ITP Support Association is a Registered Charity in England and Wales No. 1064480. It provides information and support to patients, families and health professionals affected by Immune Thrombocytopenia.

Group details last reviewed July 2018.

Headache is the most common symptom in IIH, occurring in 90 per cent of patients with this condition. It is most severe in mornings and worsens with coughing or sneezing.

Visual disturbance is reported in 35 to 80 per cent of IIH patients and includes:

• temporary vision loss or ‘blacking out’
• gradual vision reduction
• peripheral vision loss
• double vision.

These episodes can occur without the patient realising and may not be totally eliminated even with successful treatment of IIH.

Other symptoms of IIH include dizziness, nausea and tinnitus.

True benign intracranial hypertension means that there is no underlying cause but the many other possible causes of similar conditions need to be excluded. There is an association with medications given for various conditions including tetracyclin, istotretinoin, trimethoprim, sametadine, lithium, naradoxic acid and tamoxifen. If symptoms of benign intracranial hypertension develop in the presence of these medications, then they should be stopped if possible. The patient themself can help the situation by weight loss and it is reported that simply by losing weight, the symptoms can be resolved spontaneously.

The following tests are used to diagnose IIH:

• brain scan (computed tomography scan (CT)/magnetic resonance imaging (MRI)); these should be normal
• eye examination
• lumbar puncture (a process in which CSF is removed from the lower back).

IIH is monitored closely through outpatient examinations, which include regular visual testing. Headache diaries are helpful in monitoring. If an underlying cause of IIH is identified, its treatment will usually control IIH. Excess weight will need addressing and loosing seven to ten per cent of body weight may improve headaches and vision. Weight loss should be achieved through a dietician-lead calorie-controlled diet plus exercise. When there is no clear cause, IIH can be treated through lumbar punctures, medicines or surgery.

Lumbar puncture involves draining CSF from the lower back, thus reducing ICP. A lumbar puncture is performed under local or general anaesthetic, usually general anaesthetic for children. Intermittent lumbar puncture to reduce pressure is usually an effective treatment for IIH.

Treatment with acetazolamide reduces CSF production and thus reduces ICP. Other dehydrating medicines, such as furosemide, can be tried but are less effective. Steroids can also be tried as alternative.

When lumbar puncture or drug therapies are unsuccessful or when vision is deteriorating, surgical treatment will be considered. Shunts (a tube draining CSF from the brain or spine into the abdomen) can be used to reduce ICP and there are many different types available. A subtemporal decompression, a technique whereby a ‘window’ is made in the side of the skull thus reducing ICP, can also be performed. Optic nerve fenestration or decompression is another surgical option. In this procedure, slits or a large hole are placed in the optic nerve sheath and fluid drains out, thereby taking pressure off the optic nerve and preventing sight loss.

Inheritance patterns
IIH is not inherited, but may occur in families.

Prenatal diagnosis
Not applicable.

Idiopathic Intracranial Hypertension (IIH) UK

Email: info@iih.org.uk
Website: iih.org.uk

IIH UK is a Registered Charity in England and Wales No. 1143522. It provides information and support to sufferers, their families and friends. It has an online support forum and holds regional social gatherings. 

Group details last updated August 2014.

Information and support in the UK for idiopathic intracranial hypertension is also provided by SHINE (Spina Bifida•Hydrocephalus•Information•Networking•Equality; see entry Spina Bifida).

The most common presenting symptom of I/HPAH is breathlessness (dyspnea) and this is often associated with tiredness. Dizziness and fainting spells (syncope) are also typical early symptoms. Individuals may experience chest pain, palpitation (a feeling of rapid heartbeats in the chest) and a dry cough. The range and severity of symptoms varies between individuals and can occur at rest, whilst walking or during periods of mild exercise. In the more advanced stages, an individual is able to perform only minimal activity and has symptoms even when resting. Ankle or abdominal swelling may occur. In general, the more severe the symptoms, the more advanced the disease.

Pulmonary hypertension may be associated with other conditions such as pulmonary embolism (blood clots in the lungs)lung disease and heart disease. Pulmonary arterial hypertension may be associated with drugs and toxins (typically the anorexigens which are drugs used to cause weight loss in the past), some types of congenital heart disease, autoimmune disorders, portal hypertension, HIV and schistosomiasis (an infection caused by a parasitic worm).

IPAH occurs when no cause is found. Normally, oxygen-poor blood is pumped from the right ventricle, one of the pumping chambers of the heart, to the lungs via a blood vessel known as the pulmonary artery. When blood reaches the lungs, it collects oxygen and flows to the left ventricle, another pumping chamber of the heart. Oxygenated blood is pumped to the rest of the body through a blood vessel known as the aorta.

In an individual with I/HPAH, the blood pressure in the pulmonary artery (the blood vessel which carries oxygen-poor blood from the heart to the lungs) is far higher than normal. The high blood pressure is a consequence of the disease of the blood vessels in the lungs. This causes a high resistance to blood flow. In order to maintain adequate blood flow through the lungs, the heart works harder to try to force blood through the lungs. This places a strain on the right ventricle of the heart, which ultimately fails.

Changes in genes (of which BMPR2 is the commonest) have been associated with HPAH and some people with IPAH. However, many people who have the mutation do not develop pulmonary hypertension and so it has been suggested that an environmental trigger may be necessary.

The symptoms of I/HPAH are non-specific – in other words, they may be due to a number of other conditions. I/HPAH is therefore difficult to diagnose at both early and later stages. A number of imaging tests are required as well as measurement of the pressures in the heart and blood vessels (cardiac catheterisation).

I/HPAH are treated with specialist drug therapies which in the UK are prescribed by specialist pulmonary hypertension centres. There are 3 groups of drugs: prostacyclins, endothelin receptor antagonists and phosphodiesterase 5 inhibitors and they may be used in combination. These drugs improve symptoms and survival. Some patients who deteriorate on drug therapies may be considered for lung transplantation.

Inheritance patterns
Patients with I/HPAH should be advised about the availability of genetic testing and counselling. Genetic counselling and genetic testing is offered by specialist pulmonary hypertension centres to patients with IPAH considered to be sporadic or induced by anorexigens as well as to patients with a family history of pulmonary arterial hypertension.

Prenatal diagnosis
None at present.

Pulmonary Hypertension Association (PHA UK)

Tel: 01709 761 450
Email: office@phassociation.uk.com
Website: phauk.org

The Association is a Registered Charity in England and Wales No. 1120756. It provides information and support to people affected by pulmonary hypertension. The Association offers events including family weekends and conferences.  

Group details last updated April 2016.

There are several different types of ichthyosis. Some mainly affect the skin, such as:

• ichthyosis vulgaris
• X-linked ichthyosis
• congenital ichthyosiform erythroderma (also known as non-bullous ichthyosiform erythroderma)
• lamellar ichthyosis
• epidermolytic hyperkeratosis (also known as bullous ichthyosiform erythroderma)
• harlequin ichthyosis.

Others are multi-system disorders, affecting other body systems, such as the nervous or immune systems, such as:

• Netherton syndrome
• Sjögren Larsson syndrome
• Refsum disease
• trichothiodystrophies
• neutral lipid storage disease
• KID syndrome (a rare congenital disorder characterised by keratitis, ichthyosis, and deafness)
• Conradi-Hunermann syndrome.

Scaling varies in severity, from relatively mild scaling in ichthyosis vulgaris to the severe constricting plate-like scale of harlequin ichthyosis. Depending on the condition there may also be redness or blistering.

Ichthyosis is due to a mutation in a gene responsible for a normal skin structure. Each type of ichthyosis is due to a different gene mutation.

A dermatologist will diagnose ichthyosis simply from the appearance of the skin. Diagnosing the precise type of ichthyosis may require referral to other specialists and investigations such as blood tests (for genetic testing) and occasionally skin biopsy (where a small piece of skin is removed for analysis).

There is no cure for ichthyosis but the condition can be alleviated. The mainstay of treatment is to moisturise and exfoliate the skin, to minimise dryness, scaling, cracking and build-up of skin. A variety of moisturisers is available. Steroid creams are not appropriate treatment for ichthyosis. Retinoid drugs such as acitretin are beneficial for some types of ichthyosis but can have serious side effects so their use is restricted to severe cases.

Sometimes additional treatments are required, such as antiseptics or antibiotics for infection, suction clearance of the ear canal for blockage by scales, physiotherapy and night-time splinting to prevent joint contractures. Tight skin may prevent the eyelids from closing fully, so the exposed eye must be protected by lubricants and checked regularly by an ophthalmologist.

The appearance of the skin often attracts unwanted attention and remarks, causing distress to patients of all ages and their families. Counselling and psychological support should be requested if necessary.

Inheritance patterns
Some types of ichthyosis are simply passed from one generation to the next (autosomal dominant, eg ichthyosis vulgaris); X-linked ichthyosis affects only males, while females can be carriers. Most severe types of ichthyosis are inherited as autosomal recessive traits; parents appear unaffected but carry one copy of the mutant gene, while a child receiving two copies of the mutant gene will have ichthyosis. Once the type of ichthyosis has been diagnosed, patients may be referred to a clinical geneticist to discuss the inheritance pattern and risks to future pregnancies.

Prenatal diagnosis
Prenatal diagnosis is available for most severe types of ichthyosis, using chorionic villus sampling, and requires careful counselling by a clinical geneticist.

Ichthyosis Support Group

Tel: 0845 602 9202
Email: isg@ichthyosis.org.uk
Website: ichthyosis.org.uk

The Group is a Registered Charity in England and Wales No. 1142457.  It provides information and support to anyone affected by ichthyosis, and offers events and a family conference. 

Group details last updated February 2016.