Condition AZ: x

Background

Xeroderma Pigmentosum (XP) is a rare disorder where the skin has impaired ability to repair damage from ultraviolet (UV) light, including sunlight. This results in premature ageing of skin, significantly increased tendency to develop skin tumours, eye damage and in some cases neurological damage.

Credits

Last updated September 2020 by Dr Rubeta Matin, Consultant Dermatologist, Churchill Hospital, Oxford, 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?

Symptoms occur from early infancy in 50 per cent of affected individuals:

  1. Extreme sensitivity to sunlight including severe blistering sunburns
  2. Persistent redness (sunburn) even upon minimal sun exposure
  3. Marked freckling in sun-exposed areas in a child under 2 years old.

Degrees of pigmentary change of the skin occur including freckling, dryness, premature skin ageing and development of skin cancers in childhood.

UV light causes damage to the surface of the eyes including the cornea, conjunctiva and eyelids. Neurological abnormalities occur in approximately 30 per cent of patients and include learning disability (see entry Learning Disability), spasticity (stiffness or tightness of muscle), poor coordination and deafness. XP patients may be of small stature and demonstrate developmental delay.

What are the causes?

There is a defect in one of seven genes that produce proteins involved in skin repair following UV light induced DNA damage. There are at least eight different subtypes of XP; seven different genes (XP group A-G genes) are affected and an XP variant is also reported. Severity and nature of the disease relates to which gene is affected, although exceptions can occur due to different gene mutations. In general, XP group C, E and F patients (and XP variants) are spared neurological problems, whilst these variably occur in groups A, D and G.

How is it diagnosed?

The first symptoms of XP typically appear between age 1-2 years old and diagnosis is made based on skin, eye and neurological symptoms. Testing for XP involves measuring activity of DNA repair enzymes in a skin biopsy specimen taken from the upper arm. Once XP is considered a possibility, parents should reduce, if not totally avoid, UV light exposure in their child, as early avoidance can delay the onset of complications.

How is it treated?

Treatment includes rigorous protection against UV light with sunscreens, wearing of UV-blocking clothing and eyewear, and lifestyle modifications to minimise UV exposure. Patients should be monitored carefully for signs of skin cancers and treated as soon as possible. Pre-cancerous skin growths should be treated early because of their potential to become cancerous. This can involve cryotherapy (freeze-treatment), topical immunomodulators (cream/ointment applied to the affected area to alter the immune system response such as 5-fluorouracil or imiquimod) or surgery.

Vitamin D is produced by skin when exposed to UV radiation. Children who are diagnosed with XP early in life are UV-protected and have very low vitamin D levels, making them prone to bone fractures. Supplementation is recommended.

Inheritance patterns and prenatal diagnosis

Patterns of inheritance
XP is inherited in an autosomal recessive pattern. The parents of an individual with XP will be carriers of a mutation in one of the XP genes.

Prenatal diagnosis
This may be offered for families in which the disease-causing mutations have been identified. This can be performed by amniocentesis or chorionic villus sampling.

Is there support?

XP Support Group

Tel: 01494 890981
Email: info@xpsupportgroup.org.uk
Website: xpsupportgroup.org.uk

The Group is a Registered Charity in England and Wales No. 1075302. It provides information and support to people with Xeroderma Pigmentosum (XP) and other ultraviolet related disorders, and their families. The Group gives grants for UV protective equipment and products, and assists families to attend night time camps or respite in a protective environment.

Group details last updated September 2020.

Teddington Trust

Tel: 01233 645360/ 01339 883838
Email: support@teddingtontrust.com
Website: teddingtontrust.com

The Teddington Trust is a Scottish Regulated Charity no. SC045465. They provide practical and emotional support and distribute UV protective visors and gloves to patients and families affected by Xeroderma Pigmentosum, along with patient information. They offer lots of resources aimed and children, featuring the Little Ted character, which help individuals to understand their condition along with their peers. They run an in-schools educational programme for XP awareness and sun safety for all.

Group details reviewed September 2020.

Also known as: Familial Hypophosphatemic Rickets; Vitamin D Resistant Rickets

Overview

X-linked hypophosphataemia is a rare condition that causes low phosphate levels in the blood (hypophosphataemia), associated high phosphate excretion in the urine (hyperphosphaturia), and symptoms of rickets such as bowed or knock-kneed legs. Dental problems are also common. The gene that is changed (mutated) in this syndrome is called PHEX, and is located on the X chromosome. Diagnosis is made by blood tests, which show a low phosphate level and high alkaline phosphatase level. Treatment  involves improving the blood phosphate level using oral phosphate supplements, and an active vitamin D hormone such as  1-alpha D3 (alfacalcidol) or 1,25 D3 (calcitriol). Regular blood tests for phosphate and alkaline phosphatase levels, and ultrasound examination of the kidneys to check for calcium crystals as a side-effect of Vitamin D treatment, are part of the standard care associated with this condition. Occasionally, surgery is needed to shorten, lengthen, or change the angle of a leg bone. The gene causing the condition can be inherited, or the condition can occur sporadically (with no family history). Affected families should be referred to a specialist centre for information and support.

This overview is intended to be a basic description of the condition. It is not intended to replace specialist medical advice. We advise that you discuss your child’s case with a qualified medical professional who will be able to give you more detailed information.

Credits

Medical text approved January 2013 by Dr C Reid, Paediatric Nephrologist, Evelina Children’s Hospital and Dr M Champion, Contact a Family Medical Advisory Panel.

Is there support?

XLHuk

Email: via website
Website: xlhuk.org

XLHuk is a registered charity in England and Wales no.1182964. Their mission is to promote XLH and related disorders, awareness and education for affected families, medical professionals and the community at large within the UK.

Group added November 2019.

Background

XYY syndrome is a chromosomal condition which occurs only in males. A chromosome is a rod-like structure present in the nucleus of all body cells, with the exception of the red blood cells. Normally humans have 23 pairs of chromosomes, 46 chromosomes in total. The twenty-third pair are referred to as the sex chromosomes: a female has a XX pair and a male has a XY pair. A male affected by XYY syndrome has an additional Y chromosome. The additional Y chromosome may only be present in only some of the cells of the body – which is known as a mosaic form of XYY syndrome. The extent to which such an individual is affected by XYY syndrome depends upon the proportion of XYY cells to XY cells throughout the body.

Credits

Last reviewed August 2014 by Professor G Butler, Professor and Consultant in Paediatric and Adolescent Endocrinology, University College Hospital and UCL Institute of Child Health, London, UK.

What are the symptoms?

Some males with XYY syndrome show very few symptoms, whilst others may be more severely affected. Some men with XYY have mild symptoms and therefore are not diagnosed. XYY boys grow taller than average, they have a ‘growth spurt’ during childhood which results in an average height of 6 foot, 2 inches. In early childhood, XYY boys are very active, with good eating and sleeping patterns. During adolescence, they may experience severe acne.

In some cases, XYY males show learning difficulties, with slightly lower intelligence than XY males. They may have delayed speech development and have difficulties in communication.

It has been suggested that some XYY males display difficult and defiant behaviour, which usually starts in childhood. Temper tantrums are common and XYY males may be at higher risk of having problems at school. Sexual development is normal and fertility is not affected.

How is it diagnosed?

A diagnosis of XYY syndrome is made based upon a thorough physical examination, a detailed patient history, and tests to analyse the genetic make-up of the affected boy. Karyotyping involves staining chromosomes from a sample (eg a sample of cells from inside of the cheek) and viewing them under a microscope. In XYY males an extra chromosome will be seen in the cells.

How is it treated?

Management of the condition requires support for the emotional and behavioural issues that a male with XYY may experience. There is no cure for XYY syndrome. Boys diagnosed with the condition should have a speech and language assessment. Speech therapy, occupational therapy, or assistance for learning in the school setting may be of benefit. In most cases, affected males are very responsive to early intervention and treatment, and any issues may resolve altogether within a few years. Behavioural problems can be treated with therapy or medication the same as in individuals who do not have XYY syndrome.

Inheritance patterns and prenatal diagnosis

Inheritance patterns
XYY syndrome occurs sporadically (by chance) with no previous family history. It is not usually passed on from a XYY father to his sons.

Prenatal diagnosis
Chorionic villus sampling at ten to 12 weeks or amniocentesis at about 16 weeks is available during pregnancy, but is usually carried out only in mothers who are 35 years old or older.

Is there support?

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