Condition AZ: k

Also known as: Klippel-Trenaunay-Weber syndrome

Background

Klippel-Trenaunay syndrome is a rare congenital disorder of blood vessel abnormalities affecting one or more limbs. It is characterised by superficial capillary (tiny blood vessel) malformations or port wine stains (see entry Vascular Birthmarks), varicose veins (swollen and enlarged veins that are usually blue or dark purple) and hypertrophy (increased growth) of the limb. It is named after the two French doctors who described the condition in 1900.

Credits

Medical text written October 1998 by Professor J Harper. Last updated November 2010 by Professor John Harper, Consultant in Paediatric Dermatology, Great Ormond Street Hospital, London, UK.

What are the symptoms?

The port wine stain is a flat, red or purple mark on the skin that is often the only noticeable symptom of Klippel-Trenaunay syndrome at birth.

Varicose veins are generally seen along the length of the limb. The symptoms associated with varicose veins, like swelling and aching of the leg, can be reduced by wearing support stockings from an early age. There is a small risk of blood clots developing in patients with Klippel-Trenaunay syndrome. A specialist will provide appropriate advice.

The increased growth of the limb is not always noticeable at birth and needs to be monitored in early childhood. The limb can be increased in girth and length. The main functional problem relates to leg length and it is therefore important to be seen regularly by an orthopaedic surgeon if the leg length difference is significant. This becomes of concern if it is greater than 2.5 cm. In this situation, it is possible to stop the longer leg growing when the child is about 11 to 13 years old by a straightforward operation called epiphysiodesis, allowing the shorter leg to catch up. Rarely leg length asymmetry can affect the lower spine and cause backache.

Klippel-Trenaunay syndrome can be part of a more extensive complex blood vessel/lymphatic malformation. It may be associated with bleeding, for example, rectal bleeding if it involves the pelvis. It can cause significant discomfort of the limb and reduced mobility.

What are the causes?

The cause is genetic but the genetic defect of Klippel-Trenaunay syndrome has not as yet been identified, therefore genetic testing is not part of diagnosis.

How is it diagnosed?

Diagnosis is based on clinical features and most cases require ultrasound and magnetic resonance imaging (MRI), both techniques that allow images of the inside of the body to be viewed, to more accurately define the extent of the blood vessel abnormality.

How is it treated?

Medical care needs to be tailored to the individual patient and requires multidisciplinary management involving orthopaedics in relation to leg length inequality, compression bandages, laser treatment for the port wine stain, surgical intervention if appropriate and psycho-social support. The varicose veins may be helped by sclerotherapy, which involves the injection of a sclerosant liquid to chemically seal the enlarged veins.

Inheritance patterns and prenatal diagnosis

Inheritance patterns
The condition occurs sporadically as a congenital/developmental abnormality and does not seem to run in families.

Prenatal diagnosis
None.

Is there support?

Information and support in the UK for Klippel-Trenaunay syndrome is provided by the Proteus Family Network (see entry Proteus syndrome).

Also known as: Galactosylceramidase Deficiency; Galactosylcerebrosidase Deficiency; Globoid Cell Leukodystrophy

Background

Krabbe disease is a rare genetic condition in which the white matter of the nervous system degenerates. It is one of a disease group, the leukodystrophies – a term originating from the Greek, ‘leuko’ (referring to the ‘white’ matter of the nervous system); and ‘dystrophy’, which refers to imperfect growth or development. The white matter of the nervous system is composed of myelin – a fatty cover which acts as an insulator around nerve fibres. Krabbe disease may be identified by the presence of globoid cells (large scavenging cells usually with more than one nucleus) in association with a breakdown of the protective myelin coating of nerves – ultimately with loss of brain cells.

Credits

Last updated April 2015 by Professor T Cox, Professor of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, UK.

What are the symptoms?

The onset of Krabbe disease usually occurs between the ages of three to six months. Features include irritability, choking, loss of developmental and motor skills, myoclonic and general seizures (see entry Epilepsy), blindness, spasticity (stiffness of the limbs), paralysis and weight loss; unexplained fevers are noted in the last phases.

There are three stages of the condition:

  • stage I – general irritability, stiffness, arrest of motor and mental development and episodes of high temperature without the presence of an infection
  • stage II – infants may have severe arching of the back and have myoclonic-like jerks of the arms and legs, hypertonic fits, bouts of fever and loss of learned skills
  • stage III – infants are severely impaired with no voluntary movement.

The average age of death is between 13 months to 2 years, although infections and respiratory failure may bring about an earlier death.

Besides this most frequent infantile form, there are also juvenile and adult forms of Krabbe disease. These variants become apparent later, progress more slowly and those affected may live well into middle age – with perhaps only leg stiffness and sometimes painful nerve roots.

What are the causes?

The myelin sheath is a complex of many components. Krabbe disease is caused by reduced activity of an enzyme known as galactocerebrosidase (GALC), which is encoded as a gene on chromosome 14.

How is it diagnosed?

Although characteristic features of Krabbe disease may be identified in brain tissue, diagnosis of this condition is usually suspected from MRI appearances and confirmed by a special blood test that measures the activity of GALC. In some cases analysis of the GALC gene is carried out to confirm the diagnosis.

How is it treated?

Although there is no specific cure for Krabbe disease, the results of umbilical cord blood transplantation from unaffected donors has been reviewed. Neonatal transplant of umbilical cord blood significantly modifies a severe disease when given to newborn infants who are known to carry two copies of the causal gene. However, there are long-term risks from the procedure and the appearance of Krabbe disease is not prevented by this treatment. Bone marrow or now blood stem-cell transplantation (HSCT) may have a role in late-onset or adult forms of the condition where it may prevent further progression of the established disease.

Treatment of infants when manifestations are evident is limited to supportive care to control irritability and spasticity. Some symptoms, however, can be treated and physical therapy can help muscle tone and coordination.

Inheritance patterns and prenatal diagnosis

Inheritance patterns
Krabbe disease is inherited as an autosomal recessive trait and, because of this, the disorder may appear suddenly with no prior history in the family.

Prenatal diagnosis
Where requested, enzymatic and genetic tests can be used to carry out prenatal diagnosis in specialised laboratories.

Is there support?

Krabbe UK

Email: [email protected]
Website: krabbeuk.org

Krabbe UK is a Registered Charity in England and Wales No.1174472 and in Scotland No. SC047927. They provide information and support to families whose children are affected by Krabbe Leukodystrophy, champion research and raise awareness.

Group details added July 2019.

Information about all metabolic disorders is also available from Metabolic UK (see entry Inherited Metabolic diseases).

Support for the dementia aspects of Krabbe disease in adults can be obtained from the Alzheimer’s Society (see entry Alexander disease).

Background

Klippel-Feil syndrome is a rare disorder caused by failure of the division of the bones in the cervical (neck) section of the spinal column during embryonic development. Presentation may occur at any time of life and due to its variable nature it may be an incidental finding when a patient is being investigated for another reason.

Three types of Klippel-Feil syndrome have been described and these depend upon the number of vertebrae joined together and whereabouts in the spine they are joined.

Type I involves fusion of a number of bones in the neck and the upper part of the back resulting in the formation of bony blocks.

Type II is the commonest type of Klippel-Feil syndrome and involves the whole spine from the neck down to the low back. Commonly, two or three bones are joined together, but there may also be some abnormally shaped vertebrae such as hemi-vertebrae (this means the absence of half a bone).

Type III involves almost the whole of the spine from the neck down to the lower back.

Credits

Medical text written October 2002 by Contact a Family. Approved October 2002 by Dr K Metcalfe, Consultant Clinical Geneticist, St Mary’s Hospital, Manchester, UK. Last updated October 2009 by Dr K Leask, Specialist Registrar in Clinical Genetics, St Mary’s Hospital, Manchester, UK.

What are the symptoms?

Common signs are short neck, impaired movement of the head and neck especially from side to side and a low hairline at the back of the neck and low-set or underdeveloped ears. The extent to which individuals are affected by these features can vary widely, ranging from mild cosmetic concerns to more severe impairment. Those with more severe problems tend to present earlier in life.

Other features associated with Klippel-Feil syndrome include: scoliosis; spina bifida occulta, an extremely mild form of spina bifida; one shoulder blade higher than the other (sprengel deformity of the shoulder); kidney and urinary tract problems; cleft palate (see entry Cleft Lip and/or Palate); fusion of two or more ribs; problems with movements including when one side of the body is moved, the other side wanting to do exactly the same (otherwise known as mirror movements); and hearing problems (see entry Deafness). Sometimes the larynx (voice box) can be involved causing problems with vocalising.

Patients may present with symptoms at any age and therefore a diagnosis may not be made until later in life. Diagnosis is made clinically on examination of the patient, in conjunction with the specific X-ray findings. Typically, these involve at least two of the seven bones in the neck (otherwise known as the cervical vertebrae) being joined together or fused. Fusion or anomalies of vertebrae in the thoracic (chest area) or lower back may also be seen in Klippel-Feil syndrome.

Klippel-Feil syndrome is associated with conditions including MURCS Association and Wildervanck syndrome.

Only females are affected with MURCS Association. In this condition the Klippel-Feil anomaly is associated with kidney abnormality and underdevelopment of the female reproductive organs, the uterus, fallopian tubes and vagina. The problems may range from very mild, in which all the organs are present but the uterus may be slightly small or an unusual shape, to more severe when the uterus and tubes may be completely absent. Sometimes, there may actually be a double uterus and vagina. MURCS may be found to be the problem when a woman has fertility problems.

Wildervanck syndrome is also more likely to be found in females than males. The Klippel-Feil anomaly is associated with sensorineural (nerve) deafness and eye problems so that there is a squint with the eyes looking inwards. This specific eye problem associated with Wildervanck syndrome is known as Duane Retraction syndrome.

How is it treated?

Complications associated with Klippel-Feil syndrome do not normally develop before the age of 25 years and may be treated surgically. Individuals with Klippel-Feil syndrome usually have a normal lifespan. Activities that can injure the neck should be avoided.

Inheritance patterns and prenatal diagnosis

Inheritance patterns
Most cases of Klippel-Feil occur sporadically. In these cases, no other family members are affected. In a few families, Klippel-Feil syndrome is inherited as an autosomal dominant or an autosomal recessive trait.

Prenatal diagnosis
Some of the features of Klippel-Feil syndrome outlined above may be identified by ultrasound examination.

Is there support?

There is no support group for Klippel-Feil syndrome in the UK . Information and support in the UK for Klippel-Feil syndrome is provided by Metabolic Support UK (see entry Inherited Metabolic diseases).

Families can use Contact’s freephone helpline for advice and information. To meet other families with disabled children, join Contact’s closed (private) Facebook group.

If your child is affected by a medical condition or disability we can help. Call our freephone helpline on 0808 808 3555 to get information, support and advice. You can also browse our range of parent guides on aspects of caring for a disabled child in our resource library.

To meet other parents see support groups below or meet other parents online in our closed Facebook group

You may find it more helpful to search for a particular or specific kidney condition in our online A-Z of Medical Information.

Other UK sites with trusted health information:

NHS website
www.nhs.uk

Patient UK
www.patient.co.uk

Although alternative links have been selected with great care, Contact cannot accept responsibility for any inaccuracies or errors. Alternative information providers give details of their quality control procedures on their website, which includes review of information by a qualified medical professional.

Is there support?

Kidney Care UK

Tel: 01420 541 424
Email:[email protected]
Website: kidneycareuk.org

Kidney Care UK is a Registered Charity in England and Wales No. 270288. It provides information, support and grants to kidney disease patients and their families in the UK. 

Group details last reviewed September 2023.

Kidney Research UK

Helpline: 0300 303 1100
Email: [email protected]
Website: kidneyresearchuk.org

Kidney Research UK is a Registered Charity in England and Wales No. 252892. It provides information for patients, raises awareness of kidney-related issues, and funds research into the causes and prevention of kidney disease.

Group details last reviewed September 2023.

National Kidney Federation

Helpline: 0800 169 09 36
Email: via website
Website: kidney.org.uk

The Federation is a Registered Charity in England and Wales No. 1106735 and in Scotland No.SC049431. It is the national organisation for Kidney Patient Associations attached to renal units. The Federation provides information and support to kidney patients and their carers, including medical information for children and their families.

Group details last reviewed September 2023.

Also known as: Corneal ectasia

Background

Keratoconus is a progressive eye condition where the cornea (front surface of the eyeball) becomes thinned and the area then becomes conical or cone-shaped. It usually occurs asymmetrically in both eyes. The incidence is around 1 in 3,000 to 1 in 10,000 depending on ethnic groups and where in the world people live. 

Keratoconus rarely appears in an individual until puberty. Although it is uncertain how far keratoconus will develop, the condition is most unlikely to cause blindness. With the current treatment available, most people with the condition should be able to lead a normal life.

Credits

Updated October 2019 by Ms L Speedwell, Head of Optometry, Great Ormond Street Hospital and Principal Optometrist, Moorfields Eye Hospital, London, UK.

Although great care has been taken in the compilation and preparation of all entries to ensure accuracy, we cannot accept responsibility for any errors or omissions. Any medical information provided is for education/information purposes and is not designed to replace medical advice by a qualified medical professional.

What are the symptoms?

Reduced clarity of vision: An eye test will reveal increased astigmatism (spectacle prescription needed when the eye is more rugby ball shaped rather than spherical). The vision worsens as the astigmatism becomes more irregular and spectacles become less effective.

What are the causes?

The cornea becomes stretched and thin near its centre and bulges resulting in increased short-sight, astigmatism and distorted vision.

Keratoconus is often associated with atopic conditions (asthma, eczema, hayfever) and can be made worse if the eyes are itchy and rubbed a lot. It can be associated with other conditions, such as Down syndrome or it can have a genetic cause and affect other members of the family.

How is it diagnosed?

It is diagnosed using a slit lamp (special microscope) and with corneal topography (surface mapping) which shows the irregular corneal contour.

How is it treated?

People with early or mild keratoconus can often manage with spectacles or soft contact lenses but if it is more advanced, rigid contact lenses are usually necessary to improve the vision.  Contact lenses do not slow down the rate of progression but they provide good vision while being worn.

If the eyes are itchy, eye rubbing should be avoided and if necessary, treatment such as antiallergy eye drops or medication should be used.

As well as correcting the vision, regular topography scans (corneal mapping) should be carried out.  If the keratoconus is becoming worse, a treatment called corneal cross-linking (CXL) may be advisable.  CXL is a procedure where the cornea is treated with riboflavin (Vitamin B2) eye drops and ultraviolet light in order to strengthen it and slow down or halt the changes.  However, CXL is not suitable for everyone and it may not prevent keratoconus from progressing.

In a small percentage of cases, where keratoconus is advanced and contact lenses are either not tolerated or do not improve the vision sufficiently, the cornea may need to be replaced surgically with a corneal transplant or graft. Contact lenses are frequently needed after a corneal transplant to achieve good vision.

Inheritance patterns and prenatal diagnosis

Inheritance patterns
The causes of keratoconus are thought to be a combination of environmental and genetic, the latter being multi-factorial. Many cases are sporadic but some are known to be familial.

Prenatal diagnosis
Not applicable.

Is there support?

Keratoconus Self Help and Support Group

Tel: 020 8993 4759
Email: [email protected]
Website: keratoconus-group.org.uk

A Registered Charity in England and Wales No. 1057629. It provides information and support for people with Keratoconus in the UK. The Group organises regular meetings for members, holds a bi-annual conference, raises money for research and works to raise awareness of the condition.

Group details last updated October 2019.

If your child is affected by a medical condition or disability we can help. Call our freephone helpline on 0808 808 3555 to get information, support and advice. You can also browse our range of parent guides on aspects of caring for a disabled child in our resource library.

To meet other parents see support groups below or meet other parents online in our closed Facebook group

Please see below for reliable medical information on Kawasaki disease produced by alternative providers.

NHS website
www.nhs.uk/conditions

Although alternative links have been selected with great care, Contact cannot accept responsibility for any inaccuracies or errors. Alternative information providers give details of their quality control procedures on their website, which includes review of information by a qualified medical professional.

Is there support?

Kawasaki Support Group

Helpline: 02476 612 178
Email: [email protected]
Website: kssg.org.uk

A parent-led group that provides information and support to families affected by Kawasaki disease. The group offers a telephone helpline and family linking service, and promotes research into the condition.  

Group details last reviewed June 2024.

Also known as: Kabuki Make-up syndrome; Niikawa-Kuroki syndrome

Kabuki syndrome is a genetic condition that results in a typical pattern of physical and developmental problems. The facial features of the affected individuals resemble the characters in the Japanese Kabuki theatre, hence the name of the condition.

In this article

What are the symptoms of Kabuki syndrome?

Children and adults have a distinctive facial appearance with long eye openings that may slant upwards, arched eyebrows and prominent ears.

Almost half the children with Kabuki syndrome have congenital heart defects (see entry Heart Defects). Other physical features include cleft palate or palatal dysfunction (see entry Cleft Lip and/or Palate), kidney, bowel and/or dental problems. Most infants with Kabuki syndrome are hypotonic (floppy) and loose jointed. Many children require tube feeding in infancy and some need a gastrostomy. Feeding difficulties tend to resolve with age.

Young children with Kabuki syndrome are susceptible to infections, especially ear infections and many require surgery for middle ear problems. Immunological abnormalities may include ITP (see entry Immune Thrombocytopenia) and haemolytic anaemia.

Kabuki syndrome is associated with speech (see entry Speech and Language Impairment) and motor delay with mild-to-moderate learning disability. Most children require extra help in school. The degree of learning disability varies considerably, and a few individuals have almost age-appropriate general intelligence.

Some children have a growth hormone deficiency, but most children grow slowly and their final height is usually below that which would be predicted by parental heights. Many children have a head size which is below the normal range. Many individuals tend to put on weight, particularly around the trunk, from mid-childhood.

What are the causes of Kabuki syndrome?

About 55-80 per cent of patients have a mutation in the KMT2D gene (previously called MLL2), located on chromosome 12, and around five per cent have mutations in the KDM6A gene (also called UTX) located on the X-chromosome. In a small proportion of cases of Kabuki syndrome, the underlying genetic abnormality remains unknown.

How is Kabuki syndrome diagnosed?

Kabuki syndrome is usually diagnosed on the basis of the clinical and developmental features, and is confirmed by testing of the KMT2D and KDM6A genes.

How is Kabuki syndrome treated?

There is no curative treatment, but the majority of the physical problems can be treated symptomatically.

Children with Kabuki syndrome usually learn at a slower rate than normal. Special educational input can help them achieve their full potential.

Inheritance patterns and prenatal diagnosis

Inheritance patterns
In the majority of children with Kabuki syndrome, the KMT2D or KDM6A gene change is a new event (sporadic) with neither parent carrying the mutation. The recurrence risk for parents in such sporadic cases is extremely low. However, an individual with Kabuki syndrome will have a 50 per cent chance of passing the mutation to their children in every pregnancy. The effect of the mutation depends on the causative gene. If Kabuki syndrome in the individual is due to a KMT2D mutation (commoner cause) then the child who inherits the genetic change will be affected with the condition. On the other hand, if Kabuki syndrome is due to a mutation in the X-linked KDM6A gene, then the effect will depend on the gender of the child who inherits the mutation. Males are usually more severely affected with KDM6A mutation than girls. Some girls with KDM6A mutation may hardly show any problems.

Prenatal diagnosis
In families where the risk is high and where a gene change has been identified, prenatal diagnosis is now possible.

Is there support for people affected by Kabuki Syndrome and their families?

If your child is affected by a medical condition or disability, we can help. Call our freephone helpline on 0808 808 3555 to get information, support and advice. We also offer emotional support for parents via our Listening Ear service.

We have a range of parent guides on aspects of caring for a disabled child in our resource library. You may also find our Early Years Support useful, which contains links to parent carer workshops and help for families going through the diagnosis process.

We’ve listed some support groups below and you can also meet other parents online in our closed Facebook group.

Kabuki UK

Email: Via website
Website: kabukiuk.org.uk

Kabuki UK is a Registered Charity in England and Wales No. 1150972. It provides information and support to families affected by Kabuki Syndrome. The Charity raises awareness of the syndrome, provides advice to newly-diagnosed families and organises events that enable families all over the UK to get together. 

Group details last reviewed November 2020.

Credits

Last reviewed November 2020 by Dr Siddharth Banka, Consultant Clinical Geneticist, Manchester Centre for Genomic Medicine, St Mary’s Hospital, Manchester, UK.

Although great care has been taken in the compilation and preparation of all entries to ensure accuracy, we cannot accept responsibility for any errors or omissions. Any medical information provided is for education/information purposes and is not designed to replace medical advice by a qualified medical professional.

Klinefelter syndrome was first described in 1942 by Dr Harry Klinefelter and colleagues. It is a chromosomal abnormality that only occurs in 1 in 500 to 1,000 newborn boys. A female usually has an XX pair of sex chromosomes and a male an XY pair. Klinefelter syndrome occurs due to an extra copy of the X chromosome in males.

In this article

What are the symptoms of Klinefelter syndrome?

The most common symptom is infertility. Other symptoms include abnormal body proportions (long legs, short trunk, shoulder equal to hip size), less than normal amount of pubic armpit and facial hair, small, firm testicles, reduced muscle and tall stature. Breast development may appear after puberty in 25 per cent of those affected. In some cases, intellectual difficulties, especially in verbal skills, may be experienced. Additionally psychological problems with self-image may be experienced by adolescent boys and adult men.

Other chromosome abnormalities involving more than two X chromosomes in males may lead to more severe learning difficulties.

What are the causes of Klinefelter syndrome?

Males affected by Klinefelter syndrome have two X chromosomes, as well as one Y, resulting in the formation XXY. A mosaic form also occurs where only a percentage of body cells contain XXY while the remainder carry XY. The extent of the affect will depend upon the proportion of XXY to XY throughout the body. Males with Klinefelter syndrome typically have small testes that do not produce enough testosterone, which is the hormone that directs male sexual development before birth and during puberty.

How is Klinefelter syndrome diagnosed?

Klinefelter syndrome may first be diagnosed when a man comes to the doctor because of infertility, as it is the most common symptom. Examining sex chromosomes to determine number (karyotyping) can confirm the diagnosis. It may also be necessary to test hormone levels, including estradiol (a type of oestrogen), follicle stimulating hormone, luteinising hormone and testosterone.

How is Klinefelter syndrome treated?

Boys diagnosed with Klinefelter syndrome may benefit from speech and language therapy and other support to learn to express themselves. They may also benefit from educational support and occupational therapy to increase muscle tone. Testosterone therapy may be prescribed to help grow body hair, improve appearance of muscles, improve mood and self-esteem, increase energy and sex drive and increase strength.

Most men with this syndrome will be unfertile so referral to a fertility specialists for advice may be required. In some cases, surgical microdisection of the testes may reveal sperm and allow fertility using intracytopalsmic sperm inoculation or of an egg and in vitro fertilisation.

More advice from Contact

Early years support

From diagnosis and common concerns to childcare and early years education, we’re here for you and your child.

early years support

Inheritance patterns and prenatal diagnosis

Inheritance patterns
Klinefelter syndrome usually occurs as a sporadic event. Women who get pregnant after age 35 years are slightly more likely to have a boy with this syndrome than younger women.

Prenatal diagnosis
Chorionic villus sampling at 10 to 12 weeks or amniocentesis at about 16 weeks is available to older mothers to determine if the child is at risk of Klinefelter syndrome.

Is there support for people affected by Klinefelter syndrome and their families?

If your child is affected by a medical condition or disability, we can help. Call our freephone helpline on 0808 808 3555 to get information, support and advice. We also offer emotional support for parents via our Listening Ear service.

We have a range of parent guides on aspects of caring for a disabled child in our resource library. You may also find our Early Years Support useful, which contains links to parent carer workshops and help for families going through the diagnosis process.

We’ve listed some support groups below and you can also meet other parents online in our closed Facebook group.

Klinefelter Syndrome Association (KSA)

Tel: 0300 111 4748
Email: [email protected]
Website: ksa-uk.net

The Association is a Registered Charity in England and Wales No. 1058319. It provides information and support to all affected by, or having an interest in, Klinefelter’s Syndrome. The Association holds an annual conference and AGM in June and runs an activity weekend in spring and autumn. 

Group details last reviewed May 2023.

Credits

Medical text written November 1991 by Contact a Family. Approved November 1991 by Professor M Patton, Professor of Medical Genetics, St George’s Hospital Medical School, London UK and Dr JE Wraith, Consultant Paediatrician, Royal Manchester Children’s Hospital, Manchester, UK. Last updated March 2012 by Dr R Stanhope, Consultant Paediatric Endocrinologist, The Portland Hospital, London UK.