Condition AZ: a

The skull is made up of several flat, plate-like bones (cranial bones) connected by seam-like joints (sutures). These sutures allow neighbouring cranial bones to slide over each other during birth, and allow growth of the brain without restriction during childhood. The growth of the face involves similar sutures between the facial bones.

In Apert syndrome, cranial and facial sutures begin to fuse early (craniosynostosis). This early fusion alters the shape of the skull, which can raise pressure within the skull (intracranial pressure) and has consequences for development of the brain.

Children with Apert syndrome are also born with the skin and bones of the fingers and toes fused (syndactyly).

Common problems found in children with Apert syndrome include:

• abnormal shaped head and face
• malformations of the brain – these are usually fairly minor
• increased pressure inside the skull (raised intracranial pressure)
• cleft palate (see entry Cleft Lip and/or Palate)
• prominence of the eyes. The eyes can be damaged if they cannot close fully
• increased risk of ear infections, which can lead to hearing loss (see entry Deafness)
• obstruction of the airways
• dental problems related to wrongly positioned teeth
• variable learning disability – usually mild to moderate

Problems with the heart and blood vessels, stomach, intestines, kidneys and genitals can also occasionally occur.

Specific mutations in the FGFR2 gene cause Apert syndrome. This gene produces a protein that stimulates cells to develop as bone cells while the baby is developing in the womb. The mutation causes bone development to occur more rapidly than normal.

Apert syndrome is usually diagnosed by physical examination, paying particular attention to the combination of facial features and syndactyly of the fingers and toes. Associated craniosynostosis is investigated by X-rays and CT scanning, and genetic testing is used to identify the causative mutation in the FGFR2 gene.

Treatment is given to improve symptoms and prevent complications. Early diagnosis can ensure that appropriate surgical intervention is carried out.

A child with Apert syndrome will need a coordinated programme of care, and will see a number of specialists including speech therapists, orthodontists, psychologists and ophthalmologists. In the UK a number of specialist craniofacial centres are funded to provide coordinated care for children with Apert syndrome.

Inheritance patterns
Over 98% of cases arise from a new mutation; the risk for unaffected parents to have another affected child is well under 1%, if their own FGFR2 test is normal. An affected person has a 50% chance of passing the condition to each of their children.

Prenatal diagnosis
In high-risk pregnancies, prenatal diagnosis is available by chorionic villus sampling or amniocentesis, with specific testing of the FGFR2 gene. Preimplantation diagnosis would also be feasible. For lower risk pregnancies (for example, where neither partner is affected), careful ultrasound scanning from 12 weeks can provide reassurance that the baby is unlikely to have Apert syndrome. However, it should be noted that the routine 18 to 20 week scan offered to all pregnant women sometimes fails to detect the condition. Non-invasive prenatal diagnosis (NIPD) has recently become available by means of a maternal blood sample after 9 weeks of pregnancy.

Information and support in the UK for Apert syndrome is provided by Headlines (see entry Craniofacial conditions).

Individuals experience an intense sense of panic usually associated with physical sensations including breathlessness (which may lead to over-breathing), racing heart, tremor, sweating, dry mouth and faintness.  Individuals actively avoid situations which may bring them in to contact with the feared object or situation.  Even thinking about the feared object or situation can bring on a panic attack.

Anxiety can run in families, suggesting a genetic predisposition in some instances. Temperament and learning from parental behaviour is also important.  Specific adverse life experiences can trigger anxiety and phobias.  Some objects or activities seem particularly prone to produce anxiety and panic (snakes, dentists, heights) whilst others usually do not (lambs, houses).

Diagnosis is based upon the above features, sometimes with history of feared or distressing situations having produced particular anxieties, as happens in Post-Traumatic Stress Disorder.

For all forms of anxiety disorder, cognitive and behavioural psychotherapies are strongly supported by research evidence.  Medication may have a limited role in extreme circumstances, but only on a short-term basis in order to facilitate psychological approaches.  Medication should always be in addition to psychological therapies, time-limited, and as a means to an end; never an end in itself.

Inheritance patterns
There may be a familial tendency, but usually this is not the case.  Prenatal diagnosis is not possible.

Anxiety UK

Tel: 03444 775 774
Email: [email protected]
Website: anxietyuk.org.uk

The Organisation is a Registered Charity in England and Wales No. 1113403. It provides information and support to those living with anxiety disorder. Services include 1:1 therapy, and help with specific phobias.  

Group details last updated June 2019.

The condition is likely to occur because the delicate sequence of early developmental steps to form the eye is disrupted in some way. This could be because of changes in genes or through external factors acting on the developmental processes during pregnancy or a combination of the two. Anophthalmia and microphthalmia have been related to some illnesses during pregnancy such as rubella  and chicken pox. They have also been linked to some drugs taken during pregnancy, including recreational drugs and thalidomide.

Over the last few years, several genes have been described as important in anophthalmia and microphthalmia. These eye development genes include SOX2, OTX2, BMP4, RX, SHH (sonic hedgehog), CHX10 (also called VSX2), BCOR, BMP7, RAB3GAP, FOXE3, PITX2, FOXC1, MITF, HCCS, CHD7, CRYBA4, GDF6, LRP6, STRA6 and PAX6. Whilst many of these genes have only been described so far in association with a few families worldwide, SOX2 seems to be important in around 10-15 per cent of children with anophthalmia.

It is not possible to restore sight to a baby with anophthalmia affecting both eyes. However artificial eyes, usually made of acrylic and painted to look like real eyes, are used to help with the cosmetic appearance. Treatment is beneficial for these babies from a very early age, as the eye socket does not receive the correct signals to grow properly. Therefore, it is important that babies born without an eye or with a very small eye are referred for assessment at a specialist centre as soon as possible. In this way, the socket can be stimulated to grow using soft expanders or conformers as early as possible, and then artificial eyes can be fitted to improve cosmetic appearances.

Inheritance patterns
Although many cases of anophthalmia or microphthalmia appear to be isolated cases within a family, this may be due to a new change in a gene that could be passed on to future generations, or the variable expression of a change in a gene that is inherited. Therefore, it is very important for families to obtain genetic counselling.

Prenatal diagnosis
In families where a causative gene has been identified, prenatal testing may be possible. Although it may occasionally be possible to diagnose anophthalmia on an ultrasound scan after six months of pregnancy, it is very difficult to diagnose microphthalmia or related eye anomalies.

MACS (Microphthalmia, Anophthalmia and Coloboma Support)

Helpline: 0800 169 8088
Email: [email protected]
Website: macs.org.uk

The Society is a Registered Charity in England and Wales No.1161897. It provides information and support for the families of children born without eyes or with underdeveloped eyes. The Society offers financial assistance, respite holidays, practical advice around health and benefits, and has a network of regional support groups. 

Group details last updated August 2017.

Aniridia Network

Tel: 0330 120 1816
Email: [email protected]
Web: https://aniridia.org.uk/

The Aniridia Network is a Registered Charity in England and Wales no. 1176792. They support people in the UK affected by aniridia including families and professionals. The Aniridia Network organise conferences, meetups and befriending, provide access to professionals and distribute or signpost to useful information.

Group details added November 2024.

Angelman UK

Tel: 0300 999 0102
Emai: [email protected]
Website: angelmanuk.org

Angelman UK is a Registered Charity in England and Wales No. 1021882. It provides information and support to families and carers of people with Angelman Syndrome and to professionals. 

Group details last reviewed December 2025.

An affected infant has no virilisation (development of male sexual characteristics in a female), either during fetal life or during adult life. However, the presence of a testis does not allow the development of any internal female genitalia (no fallopian tubes, uterus or upper two-thirds of the vagina) despite having female external genitalia. The child is born an apparently normal girl. At puberty, the testes produce a large amount of the male hormone testosterone but, in the absence of its receptor, this has no effect. However, testosterone is converted to oestrogen and the girl will have normal breast development, without pubic or axillary hair (under the armpit), and will have no periods (as there is no uterus or vagina). Because the testes are usually found in the abdomen in girls with AIS, there is a risk of them becoming cancerous. 

This condition is caused by a genetic defect in the androgen (male hormone) receptor, which enables the male hormone, testosterone, to have its affect.

AIS is not usually diagnosed at birth. The usual presentation is during childhood with a girl who has bilateral inguinal hernias, often containing the testes. Presentation may not be until the middle teenage years, when the girl enters puberty, but has no periods and also no, or minimal, pubic or axillary hair.

The most important part of the management of AIS is the explanation and counselling given to the parents as to what and how to tell the child. This should involve an expert psychologist. Unlike partial androgen insensitivity (see below), the problem is compounded by not being diagnosed at birth. Certainly, full revealment of the diagnosis, including the chromosome abnormality, should be given by the time the child has become an adult.

The testes are usually removed when the diagnosis is made. Puberty should be induced at the normal age and then an accurate assessment of the vaginal size can be made. The assessment of whether to perform a vaginal dilation or a vaginoplasty (an operation to create a vagina) should be made by a gynaecologist who is expert in this field. Certainly, the girl should be counselled not to attempt intercourse until the vagina is an adequate size. There may be longer-term problems such as osteoporosis (see entry Osteoporosis (Juvenile)).

In partial androgen insensitivity, the genetic abnormality in the androgen receptor produces an incomplete block of male hormone action. In this case, the child is usually born with ambiguous genitalia and appears a poorly virilised male (inadequate development of male sexual characteristics). The child may be brought up as either a male or a female and the management very much depends on the severity of the condition in the individual.

Inheritance patterns
X-linked recessive

Prenatal diagnosis
This is possible, through chorionic villus sampling at ten to 12 weeks and/or amniocentesis at about 16 weeks, but seldom indicated.

Androgen Insensitivity Syndrome Support Group (AISSG)

Email: [email protected]
Website: aissg.org

AISSG is a peer support group for families and adults affected by androgen insensitivity syndrome and other XY-female conditions. It provides information, holds meetings and runs an online news group. The Group works closely with selected specialist clinicians and researchers to improve the way the conditions are dealt with, medically and psychosocially. It is in touch with several hundred affected families/individuals in the UK and has sister groups in other countries.

Group details last updated January 2016.

Anaphylaxis UK

Helpline: 01252 542 029
Email: [email protected]
Website: anaphylaxis.org.uk

Anaphylaxis UK is a Registered Charity in England and Wales No. 1085527. It provides information and support to anyone affected by anaphylaxis and the risk of severe allergic reactions. They run local support group meetings and regional medical meetings, works to educate schools, nurseries, colleges, universities and youth groups in allergy management, and provides online training programmes for families, individuals, carers and healthcare professionals. 

Group details last reviewed December 2025.

Alternating hemiplegia causes short-term weakness of either, or both, sides of the body. The attacks may alternate or sometimes overlap, meaning the second side is affected before the first recovers. The attacks last from less than an hour, which is unusual, to several days. When the attacks are prolonged, the manifestations are not apparent during sleep or for the first fifteen to twenty minutes on waking when they then return. This is a very characteristic finding and when there are bilateral attacks this may allow feeding and drinking to occur in that short clear period after waking. The episodes of hemiplegia are not epileptic in nature but epileptic seizures also occur in about half of those affected and require separate anti-epileptic drug treatment (see entry Epilepsy).

Alternating hemiplegia is now known to be caused by mutations in ATP1A3, which is one of the genes responsible for the structure of a membrane protein involved in maintaining cell function.

Clinical diagnosis is based upon display of symptoms in the first 18 months of life, though a range of tests and scans may also be carried out to rule out other conditions.

The treatment most commonly used is flunarizine (a calcium channel blocker). Other drugs have not been found to be consistently helpful. Management can be complex due to the unpredictable timing of attacks, and bilateral attacks may pose additional hazards for nutrition, hydration and breathing.

Inheritance patterns
It is autosomally recessively inherited, meaning that a person must inherit two copies of the mutated gene, one copy from each parent, to be affected by the disorder. If a person inherits just one copy of a mutated gene and one normal copy then, in most cases, the person will not be affected by the condition but is a healthy ‘carrier’

Prenatal diagnosis
It can theoretically be found by appropriate gene testing following a first case in the family, although this has never been done, and second cases are extremely rare.

Alternating Hemiplegia Support Group

Tel: 01344 560 226
Email: [email protected]
Website: ahcuk.org

The Group is a self help group, established in 1993. It provides a listening ear and holds an annual family meeting. The Group is in touch with 26 families.

Group details last updated March 2014.

HemiHelp

HemiHelp is a membership organisation supporting children and young people with hemiplegia and their families.

From 1 April 2018, HemiHelps’ services are being provided by our team at Contact.

These services include:

• The provision of information specifically for families with hemiplegia
• The online support group currently run on Facebook: HemiHelp – a Facebook group for people affected by hemiplegia
• Providing the opportunity to attend local events and workshops for families living with Hemiplegia

For more information you can email [email protected]

Group details updated April 2018.

Cone Rod Dystrophy- this is often the first symptom noticed within the first few months of life. Parents may notice that their child’s eyes are ‘wobbling’ and this is later confirmed by an ophthalmologist (eye specialist) to be nystagmus. Young people also develop photophobia and become extremely sensitive to light. The majority of young people are registered severely sight impaired by the age of five although they may retain some useful vision for some time.

Sensorineural Hearing Loss- usually detected before the age of 10 and many young children will also suffer from glue ear and a constant runny nose.

Obesity-children can put on weight rapidly despite the fact that they may eat similar portions of food to their peers. This may relate to reduced exercise ability with sensory deficits, and increased hunger.

Type 2 Diabetes– diabetes is common amongst the majority of people with Alström Syndrome from teenage onwards, and regular blood tests are carried out to detect early signs.

Dilated Cardiomyopathy– around 40% of young people may develop heart failure within the first few months of life and this is often initially thought to be the result of some kind of virus. They often tend to recover, although not completely and there is a possibility that this can re-occur in future. All people with Alström Syndrome are at risk of developing cardiomyopathy at some point in their lives.

Other symptoms may include liver and kidney disease, scoliosis, urological (urinary system) and respiratory problems.

It is important to note that not everyone diagnosed will experience all of these symptoms. Alström Syndrome should be considered if a person presents with two or more of these symptoms.

Alström syndrome is caused by mutations of the ALMS1 gene located on chromosome 2. The gene normally codes for a protein linked with a tiny hair, called a cilium, on all of our cells which also links with tubules within cells carrying receptors to the surface of the cell.

Observation of the characteristic symptoms may indicate Alström syndrome. Genetic testing can confirm the presence of a defect in the ALMS1 gene. The complex symptoms found in Alström Syndrome overlap but are distinct from those of other genetic disorders affecting cilia, and other causes of infant blindness.

Specialised multi-disciplinary clinics, funded by NHS England, are available in Birmingham to all patients throughout the UK and they provide the opportunity to be reviewed by a variety of different specialists to screen for known complications; and a number of tests are carried out.

Unfortunately there is no cure for Alström Syndrome but it is felt that these screening clinics, combined with a healthy balanced diet and regular exercise can improve the health outcomes for people diagnosed.

Inheritance patterns
Alström syndrome is inherited in an autosomal recessive manner, meaning that both parents must carry one copy of the ALMS1 gene with a significant mutation to have an affected child. Genetic testing may be possible by amniocentesis or chorionic villus sampling if the gene defect in a family is known. Genetic counselling should be sought for families affected by the condition.

Prenatal diagnosis

Prenatal testing and pre-implantation genetic diagnosis may also be available.

Alström Syndrome UK

Tel: 01803 613 117
Email: [email protected]
Website: alstrom.org.uk

The group is a Registered Charity in England and Wales No. 1071196. It provides information and support for families and individuals affected by Alström Syndrome in the UK and throughout Europe.

Group details last updated July 2016.

Boys affected by ATR-X syndrome may experience the following:

• learning disability and delayed development – boys show a varied range of learning difficulty/intellectual disability and delay in meeting developmental milestones
• lack of language – this is common with some boys only learning to sign a few words
• hypotonia (weak muscle tone) – which delays motor skills, such as sitting, standing and walking and can affect feeding as well
• distinctive facial appearance – including widely spaced eyes, a small nose with upturned nostrils and low-set ears
• alpha thalassaemia – most boys have mild signs of this. The condition reduces the production of haemoglobin which carries oxygen around the body. Sometimes red blood cells may be small in size (microcytic anaemia)
• microcephaly (small head size)
• short stature
• skeletal abnormalities
• gastrointestinal problems – gastroesophageal reflux (backflow of stomach acid into the food pipe) and constipation
• genital abnormalities – affected males may have undescended testicles, hypospadias (opening of the urethra on the underside of the penis), or ambiguous genitals (those that do not look male or female).

ATR-X syndrome is caused by a mutation in the ATRX gene. Although the exact function of the ATRX gene is unknown, it is thought to be involved in regulating the expression of other genes in the body.

How is it diagnosed?

By using a specific stain, the red blood cells of someone affected by ATR-X syndrome have a golf ball-like appearance under the microscope which allows the diagnosis of ATR-X to be confirmed by a simple blood test in 85% of cases.

Testing the DNA to look for the change (mutation) in the ATRX gene can confirm the diagnosis.

Boys affected by the condition require support in various areas to develop to their full potential. Infant stimulation, early intervention and special education are very important to encourage development. Alternative forms of communication, such as signing, PECS and Makaton may be used. Infantile hypotonia is common and is associated with difficulty sucking, so extra nutritional support may be needed (such as special teats and tube feeding into the stomach). Medications may be used to alleviate gastroesophageal reflux. Physical therapy may be needed to help movement and also relieve spasticity (tightness in muscle) if it occurs.

The anaemia associated with alpha thalassaemia is usually mild and very few cases need treatment. Undescended testes should be monitored with scanning, as the testicles may become cancerous if left inside the abdomen.

Inheritance patterns
This condition is transmitted in an X-linked recessive manner. Affected families should be referred to a genetics centre for information and support.

Prenatal diagnosis
This may be possible in some families where the mutation in the family has been identified.

ATR-X Support Group

Tel: 01606 44943
Email: [email protected]

The group offers support for people affected by Alpha Thalassaemia and their families. It links families where possible, and welcome calls from anyone with an interest in this condition.

Group details last updated January 2016.

There is a very active international Facebook page for affected families. It’s a closed group but can be reached at: https://www.facebook.com/groups/163849465337/

Alopecia UK

Tel: 0800 101 7025
Email: [email protected]
Website: www.alopecia.org.uk

The Organisation is a Registered Charity in England and Wales No. 1111304. It provides information, advice and support for people with all types of alopecia, including information for children and young people. The website offers information, a discussion forum, and details of local or online support groups across the UK.

Group details last reviewed December 2025.

Allergy UK

Tel: 01322 619 898
Email: [email protected]
Website: www.allergyuk.org

Allergy UK is a Registered Charity in England and Wales No. 1104845 and Scotland No: SC039257. It provides information and support for allergy sufferers in the UK through its dedicated helpline, support network and online forum for those with allergy and intolerance.  

Group details last reviewed December 2025.

AKU may discolour the outer ears, nose and whites of the eyes with bluish-black pigment. Vision is not affected. The teeth and nails may also be a bluish-black colour. A dusky discolouration on the skin of the hands may be apparent. Pigment appears when individuals perspire, causing discolouration of clothing. Homogentisic acid (HGA) accumulated in the urine causes it to turn black. Darkening may not occur for several hours after urinating and many individuals never observe any abnormal colour in their urine. In later life, AKU may affect the heart, kidney and prostate. The condition does not cause developmental delay or cognitive impairment and lifespan of affected individuals is generally not reduced.

AKU is caused by the deficiency of an enzyme known as homogentisic acid oxidase (HGAO). Normally, this enzyme performs a crucial step in a metabolic pathway by converting a chemical, homogentisic acid (HGA), into another form to meet the body’s needs. As normal amounts of the HGAO enzyme are missing, HGA is not broken down and accumulates in the body. Some is eliminated in the urine, and the rest is deposited in body tissues where it is harmful. The result is ochronosis (a blue-black discolouration of connective tissue, including bone, cartilage and skin.

The build-up of HGA leads to premature progressive degeneration in the joints. Chronic joint pain is one of the first symptoms of AKU. Arthritis of the spine, knees and hips causes symptoms of stiffness, pain, swelling and limited motion. Males tend to have an earlier onset of arthritic symptoms with a greater degree of severity than females. Deposits of pigment may cause cartilage to become brittle and eventually to fragment.

High degree of alertness is needed to recognise that black urine even early in life may be due to alkaptonouria. The presence of black urine in an older person with pigment in eye and ear should alert a clinician to consider the diagnosis. It can be confirmed by a simple urine test for high levels of HGA in a reliable laboratory.

The main treatment at present is pain killers. When this fails, joint replacement will be required. There are at present no other approved treatments for AKU.

Inheritance patterns
AKUis inherited in an autosomal recessive manner. Changes in the HGD gene on chromosome 3 are associated with the features of AKU. This condition was one of the first ‘inborn errors of metabolism’ discovered and one of the first conditions for which recessive inheritance was proposed.

Prenatal diagnosis
This may be possible and further information, including genetic counselling, should be sought from a doctor.

Alkaptonuria Society (AKU Society)

Tel: 01223 322 897
Email: [email protected]
Website: www.akusociety.org

The Society is a Registered Charity in England and Wales No. 1101052. It provides information and support to individuals and families affected by alkaptonuria (AKU).

Group details last updated August 2016.

The infantile form generally appears by age two, with features including megalencephaly (large head), developmental delay, persistent vomiting, weight loss, seizures, muscle stiffness and reduced movement. Hydrocephalus (water on the brain) may be present, sometimes picked up by antenatal ultrasound scans.

The juvenile form appears slightly later, around 3-12 years old, with trouble speaking or swallowing, possibly psychiatric problems, but rarely seizures.

The adult form is the most varied and can occur from 13-70 plus. Symptoms may appear gradually, and include difficulty eating or speaking, very early or late puberty, deterioration of cognition (reasoning, memory or attention), changes in walking pattern, palatal myoclonus (spasm of the roof of the mouth), nystagmus (uncontrolled eye movements), sleep apnoea, bowel or bladder problems, and kyphoscoliosis (curving of the spine). Some adults are misdiagnosed with Multiple Sclerosis (MS) or Alzheimer’s Disease.

Symptoms are caused by failure of nerve signals in the brain. This occurs because the myelin sheaths surrounding nerve axons degenerate, disrupting electrical conduction. This is comparable to the plastic coating of electrical cables wearing down, allowing damage to the wires inside. The first step happens in astrocyte cells,which are important for supporting the normal function of neurons (nerve cells) and oligodendrocytes (which make myelin). Alexander disease is caused by a change in the GFAP gene, producing abnormal GFAP proteins, which clump together with healthy proteins and form structures called Rosenthal fibres.These fibres cause damage themselves, but may also cause problems through ‘mopping up’ normal, healthy GFAP or other proteins which are important for the healthy functioning of astrocyte cells.

If Alexander Disease (AxD) is suspected based on symptoms, patients may have blood tests to rule out other conditions, a magnetic resonance imgaging(MRI) scanto look for the specific pattern of myelin deterioration, and agenetic testto look at the GFAP gene, using a blood or saliva sample. Some (generally older) children have less typical symptoms, which could make diagnosis more difficult. In 5% of people with AxD, no GFAP mutation is found, possibly because it is missed by the test, or because another gene is mutated (changed), with an indirect effect on GFAP function.

Alexander disease is managed by supporting the patient / family to maximise quality of life. This may include physiotherapy, seizure medication, anti-sickness medications or feeding tubes. Unfortunately, there is currently no treatment available to prevent the disease progressing and most patients will have a severely shortened lifespan, with some children only surviving a few years. The exact life expectancy is dependent on individual circumstances.

Inheritance patterns
Alexander disease is occasionally inherited (less than 0.1 per cent), so affected families may want genetic testing. 

Prenatal diagnosis
If there is a risk of future children being affected, antenatal genetic testing may be possible by chorionic villus sampling or amniocentesis.

Information and support in the UK for Alexander disease is provided by Metabolic Support UK (see entry Inherited Metabolic diseases). Support for dementia can be obtained from the Alzheimer’s Society.

Alzheimer’s Society

Helpline: 0300 222 11 22
Email: via website
Website: www.alzheimers.org.uk

TThe Society is a Registered Charity in England and Wales No. 296645, established in 1979. It offers information and advice on all forms of dementia and a network of carers groups, carers’ contacts, befriending projects and helpline. It publishes a monthly newsletter and has information available. The Society has over 25,000 members.

Group details last confirmed June 2017.

AHO with pseudohypoparathyroidism (PHP) In addition to AHO, in PHP the body is unable to respond to various hormones. One such hormone is parathyroid hormone (PTH), which maintains levels of calcium and phosphate in the blood. In PHP, parathyroid hormone is produced in normal or increased amounts by the parathyroid glands and released into the blood. However, the body is resistant to its effects causing hypocalcaemia (low calcium levels), and hyperphosphatemia (high phosphate levels). Signs of hypocalcaemia include tingling in the fingers, muscle cramps, possible seizures (fits) and, in the longer term, cataracts. Hypocalcaemia typically begins in mid-childhood. Individuals with PHP are often resistant to thyroid stimulating hormone (TSH), which makes the thyroid gland produce thyroid hormone. The effects of lack of thyroid hormone are a tendency to gain weight easily and to feel the cold, dry skin and hair, and a lack of energy.

Pseudo-pseudohypoparathyroidism (PPHP) People with this condition have the physical characteristics of AHO but they do not have any hormone abnormalities (that is, they just have AHO). The complicated name arose for historical reasons.

Mutations in a gene called GNAS1 carried on chromosome 20 cause these conditions. Pseudohypoparathyroidism can also occur on its own without AHO and is caused by a different type of genetic change affecting the same GNAS1 gene.

The physical features of AHO are diagnosed by examination usually by an experienced clinical geneticist or endocrinologist. It may be necessary to do X-rays particularly of the hands, feet and spine to confirm the diagnosis. Many of the features of AHO are not specific to this condition, that is, they can have many different causes of which genetic changes in the GNAS1 gene are only one. Chromosome testing may be requested to look for some other conditions that can resemble AHO.

PHP is diagnosed by testing of the blood and urine for biochemical changes associated with resistance to PTH and TSH, such as low calcium, raised phosphate, high PTH, low thyroxine and high TSH levels. In people in whom the diagnosis is strongly suspected, specific testing for genetic changes (mutations) in the GNAS1 gene is available, which picks up an abnormality in about 70 per cent of affected people. 

Fortunately, the low calcium levels experienced with this condition can be treated with vitamin D, and low thyroid levels can be treated with thyroxine.

Inheritance patterns
AHO is inherited as an autosomal dominant trait but the presence or absence of PHP depends on the parent of origin. We each have two copies of the GNAS1 gene, one from each parent. People with AHO have a mutation (genetic change) in one GNAS1 gene copy. If the copy with the mutation is the one they inherited from their mother, they usually have associated PHP. If it is the one they inherited from their father then they do not usually have any hormone abnormalities (that is, they have PPHP).

A person with AHO has a 50 per cent chance in each pregnancy that their baby will inherit the GNAS1 mutation, regardless of the sex of the baby. However, many individuals with AHO have unaffected parents because the mutation has arisen sporadically.

Prenatal diagnosis
AHO can be tested for using chorionic villus sampling or amniocentesis during pregnancy, but only if the specific genetic change causing AHO in the family has been identified. Genetic counselling is strongly recommended for individuals and families affected by this condition.

There is no support group for Albright hereditary osteodystrophy in the UK. Cross referrals to other entries in The Contact a Family Directory are intended to provide relevant support for those particular features of the disorder. Organisations identified in those entries do not provide support specifically for Albright hereditary osteodystrophy.

Families can use Contact’s freephone helpline for advice, information and, where possible, links to other families.

There are two main types of albinism:

Ocular albinism (OA)
Predominantly affects the eyes, with affected individuals often having only slightly lighter skin and hair colour than other family members and it usually leads to nystagmus (see entry). Many individuals may have been given a diagnosis of ‘idiopathic nystagmus’, meaning that the cause is unknown.

Oculo-cutaneous albinism (OCA)
Affects the eyes and skin to a very variable extent.

There are rare variants of OCA:

• Hermansky-Pudlak syndrome – this presents with easy bruising and affected individuals may have lung, bowel and bleeding features
• Chediak-Higashi syndrome – in which there is an increased susceptibility to infection and bleeding.

Most individuals with albinism do not have any associated health problems.

Albinism is caused when there is a fault in one of the many different genes that control the production of melanin and the development of the eye and vision pathways.

Diagnosis can be made by the observation of the characteristic features of the disorders. An ophthalmologist will be involved in identifying the ocular features (those related to the eyes). In some cases that are not obvious, especially if the individual has some pigmentation, the characteristic abnormalities of the visual system are confirmed by a visually evoked potential (VEP) test. This test shows a detailed record of electrical activity in the visual pathways to the brain. Genetic tests are not yet available except rarely on a research basis.

Treatment for albinism is symptomatic and aims to reduce the problems caused by the disorder. High sun protection factor (SPF) sunscreen, sun glasses and clothing to protect the skin can all be helpful.

A range of telescopic and microscopic optical devices can provide great improvement in visual acuity by spreading the features of the object being viewed over a larger area of the abnormal macula (the central part of the retina).

Inheritance patterns
Ocular albinism is X-linked or autosomal recessive. OCA is autosomal recessive. Genetic counselling should be sought by families who are affected by the condition.

Prenatal diagnosis
Not currently available.

Albinism Fellowship

Helpline: 01282 771 900
Email: [email protected]
Website: www.albinism.org.uk

The Fellowship is a Registered Charity in Scotland No. SC009443. It provides information and support for people with albinism and their families in the United Kingdom and Ireland.

Group details last updated December 2014.