Clinical Diagnosis

The diagnosis of Alström syndrome is based on cardinal clinical features that emerge throughout infancy, childhood, and young adulthood (see Table 1 and Figure 1).

Figure

Figure 1. Age Range of Onset of Features in Alström Syndrome.

Cardinal features that evolve as patients age are as follows [Marshall et al 2005]:

Major features

• Cone-rod dystrophy with secondary nystagmus and photodysphoria (light sensitivity/photophobia) occurs within the first year of life.

• Obesity, primarily truncal with a body mass index (BMI: kg/m²) greater than 25 or greater than the 95th centile, develops in early childhood.

• Progressive bilateral sensorineural hearing impairment usually develops between ages one and ten years, but onset can be variable. The hearing impairment is initially in the high frequency range.

• Dilated cardiomyopathy with infantile onset or restrictive cardiomyopathy in adolescents and adults occurs in more than 60% of affected individuals.

• Pulmonary disease ranges in severity from frequent bronchial infections to pulmonary fibrosis and pulmonary hypertension.

• Insulin resistance/type 2 diabetes mellitus. Insulin resistance ranges from hyperinsulinemia to glucose intolerance to type 2 diabetes mellitus, depending on the age of the individual. Type 2 diabetes can develop in childhood or adolescence.

• Hepatic disease is variable, ranging from elevated transaminases to cirrhosis and liver failure. Steatohepatitis, enlarged liver and spleen, and extensive fibrosis are described.

• Renal disease is progressive; severity of the glomerulosclerosis is highly variable.

Minor features

• Hypothyroidism

• Dental abnormalities

• Flat feet

• Urological dysfunction

• Developmental delay

As described in Marshall et al [2007a], diagnostic criteria have been revised to take the age of the patient into consideration (Table 1).

Molecular Genetic Testing

Gene. ALMS1 is the only gene currently known to be associated with Alström syndrome. Mutations include missense and nonsense mutations, insertions, deletions, and splice site disruptors.

Clinical testing

Sequence analysis of select exons. Sequence analysis of entire exons 10 and 16 and partial exon 8 detects mutations in 25%-40% of individuals with Alström syndrome [Collin et al 2002, Hearn et al 2002, Titomanlio et al 2004, Marshall et al 2007a].

Sequence analysis of the entire coding region. In a study of 12 individuals from the UK in which Minton et al [2006] sequenced the entire coding region; both mutations were identified in 8/12, one mutation in 2/12, and no mutation in 2/12.

Although there is no evidence for locus heterogeneity in Alström syndrome, possible other explanations for the low mutation detection frequency include the following:

• Sequence analysis of select exons (16, 10, and 8) does not detect mutations in the remainder of the coding region or intronic alterations.

• Deletions of an entire exon have been observed in some affected individuals [Author, personal observation].

• Diagnostic confusion may exist between Alström syndrome and other disorders such as Bardet-Biedl syndrome (BBS) (see Differential Diagnosis).

Research testing. For labs performing research on this disorder, click here.

Table 2. Summary of Molecular Genetic Testing Used in Alström Syndrome

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Gene Symbol	Test Method	Mutations Detected	Mutation Detection Frequency by Test Method 1	Test Availability
ALMS1	Sequence analysis of exons 16, 10, and partial 8	Sequence variants 2	25%-40%	Clinical
	Sequence analysis of entire coding region	Sequence variants 2	Unknown

Test Availability refers to availability in the GeneTests™ Laboratory Directory. GeneReviews designates a molecular genetic test as clinically available only if the test is listed in the GeneTests™ Laboratory Directory by either a US CLIA-licensed laboratory or a non-US clinical laboratory. GeneTests does not verify laboratory-submitted information or warrant any aspect of a laboratory's licensure or performance. Clinicians must communicate directly with the laboratories to verify information.

1. The ability of the test method used to detect a mutation that is present in the indicated gene

2. Examples of mutations detected by sequence analysis may include small intragenic deletions/insertions and missense, nonsense, and splice site mutations.

Interpretation of test results

• Given the current detection rate, failure to identify a disease-causing sequence variant does not preclude the diagnosis of Alström syndrome.

• For issues to consider in interpretation of sequence analysis results, click here.

Testing Strategy

Confirming/establishing the diagnosis in a proband. The diagnosis of Alström syndrome relies primarily on clinical findings. In some instances the diagnosis can be confirmed by molecular genetic testing.

Carrier testing for at-risk relatives requires prior identification of the disease-causing mutations in the family.

Note: Carriers are heterozygotes for this autosomal recessive disorder and are not at risk of developing the disorder.

Prenatal diagnosis and preimplantation genetic diagnosis (PGD) for at-risk pregnancies require prior identification of the disease-causing mutations in the family.

Note: It is the policy of GeneReviews to include in GeneReviews™ chapters any clinical uses of testing available from laboratories listed in the GeneTests™ Laboratory Directory; inclusion does not necessarily reflect the endorsement of such uses by the author(s), editor(s), or reviewer(s).

Genetically Related (Allelic) Disorders

No other phenotypes are known to be caused by mutations in ALMS1.

Natural History

A wide range of clinical variability is observed among individuals with Alström syndrome, including among sibs [Hoffman et al 2005]. The first clinical presentation of Alström syndrome (Table 3) is usually nystagmus caused by cone-rod dystrophy and resulting in childhood blindness. Disease characteristics that are a bit later in onset include truncal obesity that manifests during the first year of life, progressive sensorineural hearing loss, infantile-onset dilated cardiomyopathy or later-onset restrictive cardiomyopathy, insulin-resistant type 2 diabetes mellitus, and hepatic and renal dysfunction.

Cone-rod dystrophy. Between birth and age 15 months visual problems present as progressive cone dystrophy resulting in visual impairment, photophobia, and nystagmus. Electroretinography (ERG), required to establish the diagnosis of cone-rod dystrophy, is abnormal from birth, eventually with impairment of both cone and rod function. Rod function is preserved initially but deteriorates as the individual ages, with visual acuity of 6/60 or less by age ten years, increasing constriction of visual fields, and no light perception by age 20 years. The severity and age of onset of the retinal degeneration vary among affected individuals [Malm et al 2008].

Fundus examination in the first decade may be normal or may show a pale optic disc and narrowing of the retinal vessels. Posterior subcapsular cataracts are common.

Obesity. Children with Alström syndrome have normal birth weight. Hyperphagia and excessive weight gain (some studies show weight gain greater than expected for intake) begin during their first year, resulting in childhood truncal obesity. In some individuals body weight tends to normalize, decreasing into the high-normal to normal range after adolescence.

Progressive bilateral sensorineural hearing loss. Hearing loss may be detected as early as age one year, initially in the high frequency range. Progressive sensorineural hearing loss presents in the first decade in as many as 70% of individuals with Alström syndrome. Hearing loss may progress to the severe or moderately severe range (40-70 db) by the end of the first to second decade [van den Abeele et al 2001]. A high incidence of glue ear (long-standing sticky fluid in the middle ear) can additionally lead to a conductive hearing loss [Marshall et al 2005].

Cardiomyopathy. More than 60% of individuals with Alström syndrome develop congestive heart failure as a result of cardiomyopathy at some stage of their lives. Onset, progression, and clinical outcome of the cardiomyopathy vary, even within families [Makaryus et al 2003, Hoffman et al 2005].

More than 40% of affected infants have a transient but severe dilated cardiomyopathy with onset between age three weeks and four months [Marshall et al 2005]. Most of these children survive and make an apparently full recovery in infancy. At a later age about 10%-15% of these have spontaneous recurrence of a progressive restrictive cardiomyopathy. The proportion of those with Alström syndrome who develop infantile-onset cardiomyopathy may be underestimated because some infants who succumb early may have undiagnosed Alström syndrome.

About 20% of individuals with Alström syndrome have later-onset progressive restrictive cardiomyopathy identified between the teens to late 30s. Postmortem myocardial fibrosis has been described [Marshall et al 2005]. Cardiac magnetic resonance imaging suggests myocardial fibrosis may be present in clinically affected and asymptomatic individuals [Loudon et al 2009].

Insulin resistance/type 2 diabetes mellitus. Diabetes mellitus in Alström syndrome is the result of tissue resistance to the actions of insulin, as demonstrated by an elevated plasma insulin concentration and glucose intolerance that usually present in childhood. The age at which type 2 diabetes mellitus develops varies; it may be as early as age five years. Type 2 diabetes mellitus and insulin resistance are typically accompanied by the skin changes of acanthosis nigricans, i.e., velvety hyperpigmented patches in intertriginous areas.

In a small study of 12 unrelated individuals with Alström syndrome, obesity (BMI and waist circumference) decreased with age, whereas insulin resistance increased with age [Minton et al 2006].

Hyperlipidemia. Hyperlipidemia is primarily hypertriglyceridemia, but can sometimes include high serum concentration of total cholesterol. Affected individuals are at risk for sudden increase in triglycerides precipitating life-threatening pancreatitis [Wu et al 2003].

Developmental delay. About 20% of affected individuals have delay in early developmental milestones including delays in gross and fine motor skills and in expressive and receptive language, and about 30% have a learning disability. Cognitive impairment (IQ <70) is very rare.

Short stature. Growth rates for young children are normal, but accelerated skeletal maturity (2-3 years advanced bone age) and low-serum growth hormone concentrations result in adult stature that is typically less than the 25th centile. In about 98% of individuals over age 16 years height is below the fifth centile [Maffei et al 2007].

Scoliosis or kyphosis, beginning in puberty, is common [Maffei et al 2002].

Hypogonadotropic hypogonadism. The onset of puberty is sometimes delayed in males, but secondary sexual characteristics are usually normal. Male hypogonadotropic hypogonadism results in low plasma testosterone concentration secondary to low plasma gonadotropin concentration. Atrophic fibrotic seminiferous tubules are described [Marshall et al 2005]. Males with hypogonadotropic hypogonadism often have a small penis, and usually have small testes, often with gynecomastia in adolescence.

Endocrine disturbances in females include reduced plasma gonadotropin concentrations, hirsutism, cystic ovaries, precocious puberty (pubertal onset before age 8 years), endometriosis, irregular menses, or amenorrhea. External genitalia are normal in females.

Reports of individuals with Alström syndrome who have reproduced are extremely rare.

Urologic disease. Urinary problems of varying severity affect approximately 50% of individuals with Alström syndrome. Urologic disorders of varying severity, characterized by detrusor-urethral dyssynergia (lack of coordination of bladder and urethral muscle activity), have been described. The greatest problems appear to occur in females in their late teens. Minor symptoms include urgency and long intervals between voiding, which suggests a decrease in bladder sensation, hesitancy, and poor urinary flow. Moderate symptoms include urinary frequency, incontinence, and symptoms associated with recurrent infections. More severe urinary symptoms include worsening urinary incontinence or retention; these symptoms may alternate.

Lower abdominal and perineal pain is common and may relate to abnormal bladder/sphincter function [MacDermott 2001].

Renal disease is common, slowly progressive, and highly variable; it manifests as tubulo-interstitial disease resulting from interstitial fibrosis. Initial signs of mildly elevated serum concentrations of creatinine and blood urea nitrogen (BUN) may be followed by polyuria and polydipsia resulting from a concentrating defect. Onset can be in mid-childhood through adulthood. End-stage renal disease (ESRD) can occur as early as the mid- to late teens.

Renal biopsy often shows interstitial fibrosis, glomerular hyalinosis, and tubular atrophy [Marshall et al 2005]

Hepatic disease. Elevated plasma concentration of liver enzymes is common in early childhood. Macrovesicular steatosis can be present or absent. Progression to hepatic failure can occur in the second to third decades. Hepatomegaly and its complications of portal hypertension, ascites, splenomegaly, and esophageal varices are also seen.

Liver biopsies and postmortem examination have revealed varying degrees of steatohepatitis, hepatic fibrosis, cirrhosis, chronic nonspecific active hepatitis with lymphocytic infiltration, patchy necrosis, and fatty liver [Quiros-Tejeira et al 2001, Marshall et al 2005].

Gastrointestinal disease. General GI disturbances such as epigastric pain and gastroesophageal reflux disease (GERD) are common.

Pulmonary involvement. Pulmonary symptoms include chronic bronchitis, frequent pneumonia, chronic obstructive pulmonary disease (COPD), and pulmonary hypertension. Moderate to severe interstitial fibrosis has been reported [Marshall et al 2005]. In some cases, acute hypoxia, probably resulting from a combination of pulmonary fibrosis and severe scoliosis, has caused sudden death.

Other

• Scoliosis and kyphosis of varying severity are reported in 30%-70% of individuals with Alström syndrome [van den Abeele et al 2001, Marshall et al 2005].

• Severe flat feet and dental abnormalities have been observed [Marshall et al 2005].

• Hypothyroidism has been reported in nearly 20% of individuals [Marshall et al 2005]; hyperthyroidism infrequently occurs [Ozgül et al 2007].

• Neurobehavioral manifestations such as absence seizures, excessive startle response, severe and unexplained peripheral pain, and mild autistic spectrum behaviors have been reported [Marshall et al 2005].

Genotype-Phenotype Correlations

A genotype-phenotype association study of 58 affected individuals [Marshall et al 2007b] found suggestive associations between disease-causing variants in exon 16 of ALMS1 and the following findings:

• Onset of retinal degeneration before age one year (P=0.02)
  
  AND

• Occurrence of urologic dysfunction (P=0.02), diabetes mellitus (P=0.03), and dilated cardiomyopathy (P=0.03)

A more significant association was found between alterations in exon 8 and absent, mild, or delayed renal disease (P=0.0007). This preliminary observation may have implications for the understanding of how alternative splicing of ALMS1 contributes to the severity of the disease and provide useful information to clinicians.

Prevalence

About 700 individuals diagnosed with Alström syndrome are known worldwide.

Ethnically or geographically isolated populations have a higher-than-average frequency of Alström syndrome [Deeble et al 2000, Ozgül et al 2007, Aldahmesh et al 2009].

Evaluations Following Initial Diagnosis

To establish the extent of disease in an individual diagnosed with Alström syndrome, a complete history of disease should direct detailed physical examination and investigations.

• Cone-rod dystrophy. Ophthalmologic evaluation, including electroretinogram and visual field testing

• Obesity. Measurement of weight and height; calculation of body mass index (BMI)

• Progressive sensorineural hearing loss. Audiometry and otoacoustic emissions (OAE) to detect sensorineural or conductive hearing loss; assessment of otitis media and conductive hearing loss

• Dilated cardiomyopathy. A detailed cardiac history and examination, including auscultation, echocardiography and ECGs. Echocardiography is required to demonstrate ventricular dilatation, fibrosis, and decreased myocardial function.

• Insulin resistance/type 2 diabetes mellitus

  • Fasting plasma glucose, even in infancy

  • A glucose tolerance test (GTT) as early as age six years

  • Plasma insulin concentration, as hyperinsulinemia may be present from infancy

• Hyperlipidemia. A fasting lipid profile, including triglycerides

• Endocrine abnormalities

  • Assessment of thyroid function

  • Measurement of pituitary hormones

• Urologic

  • History of urinary difficulties

  • If the individual is symptomatic or if urinalysis is abnormal, renal ultrasound examination to detect pelvi-calyceal dilatation and bladder ultrasound examination to measure post-voiding residual volumes

• Renal disease

  • Baseline blood pressure

  • Measurement of plasma BUN, creatinine, urea, and electrolytes. If renal function testing is abnormal, ultrasound examination. If abnormalities, refer to a nephrologist.

• Hepatic disease

  • Measurement of plasma ALT, AST, and GGT concentration

  • Liver ultrasonography to evaluate for possible hepatomegaly and portal hypertension

  • If clinically indicated, screening esophagogastroduodenoscopy for varices

• Pulmonary disease. Detailed assessment of pulmonary function by chest radiography, combined with pulmonary function tests

• Developmental assessment. Educational evaluation for intervention and IEP

• Other

  • Thyroid abnormalities. Measure plasma TSH, T4, and T3 concentrations.

  • Gastrointestinal. If symptoms of reflux esophagitis are present, perform barium swallow or upper gastrointestinal endoscopy.

  • Skin. Note acanthosis nigricans (indication of insulin resistance/diabetes mellitus), alopecia, body hair, hirsutism on physical examination.

  • Orthopedic abnormalities. Note flat feet, scoliosis, barrel chest, kyphoscoliosis on physical examination.

  • Neurologic manifestations. Examine for absence seizures, autistic-spectrum behavioral abnormalities, excessive startle, partial unilateral paralysis, unexplained joint or muscle pain, muscle dystonia, or hyporeflexia.

Treatment of Manifestations

No therapy exists to prevent the progressive organ involvement. However, monitoring for developing problems and early intervention is essential.

Rod-cone dystrophy

• Early on when photodysphoria is significant, the use of red-tinted prescription lenses may reduce symptoms.

• Early educational planning should be based on the certainty of blindness. Instruction in the use of Braille, mobility training, adaptive living skills, and computing skills (including voice recognition and transcription software), and the use of large print reading materials while vision is still present are crucial.

Obesity. A healthful, reduced calorie diet and regular exercise, such as walking, hiking, biking, and swimming with adaptations for the blind, are recommended to control weight gain.

Progressive sensorineural hearing loss

• Myringotomy has been helpful in individuals with recurrent "glue ear."

• Hearing can be maximized with bilateral digital hearing aids.

• Cochlear implantation has benefitted some patients.

Cardiomyopathy. Angiotensinogen-converting enzyme inhibitors, diuretics, digoxin, and possibly beta-blockers should be used in the treatment of cardiac failure.

Insulin resistance/type 2 diabetes should be treated as in the general population unless heart failure and/or liver dysfunction are present. The diabetes mellitus is very insulin resistant, but some individuals respond to a low-sugar, low-fat diet; exercise; and metformin. Glitazones are added to further reduce insulin resistance but must be avoided in the presence of active or treated heart failure. These treatments should be discontinued when the serum creatinine concentration exceeds 200 µmol/L or if cardiomyopathy is evident.

Hypertriglyceridemia

• High-dose statins may reduce serum triglycerides, as can nicotinic acid, although the latter is not as well tolerated.

• Fibrates have been ineffective in a few cases.

• Pancreatitis should be treated as in the general population.

Hypogonadotropic hypogonadism. If abnormalities in pubertal development or menstrual abnormalities are present on physical examination, the affected individual should be referred to an endocrinologist with expertise in sexual developmental abnormalities.

Urologic. Some individuals have required urinary diversion or self-catheterization to manage voiding difficulties [MacDermott 2001].

Renal disease

• The use of angiotensinogen-converting enzyme (ACE) inhibitors may be considered if proteinuria is detected.

• Successful renal transplantation has occurred in a few individuals, although can be contraindicated in the presence of other complications including morbid obesity, uncontrolled diabetes, and cardiomyopathy.

Hepatic disease. Portal hypertension may be treated with beta-blockade and sclerotherapy of the esophageal veins. Banding should be done in order to prevent upper GI hemorrhage from varices. Patients who fail to respond to medication and banding are candidates for a transjugular intrahepatic portosystemic shunt (TIPS) to decrease risk of variceal bleeding caused by portal hypertension. Patients with significant portal hypertension should be evaluated early for liver transplantation.

Pulmonary disease. Chronic obstructive airway disease and associated infection should be managed in line with appropriate national guidelines.

Other

• As children approach puberty, gonadotropin and pituitary hormones should be assessed to determine if hormonal adjustments are necessary.

• If skeletal abnormalities are present, referral to an orthopedist is appropriate.

• Thyroxine therapy should be initiated and monitored if the individual is hypothyroid.

• Reflux esophagitis, skin manifestations, orthopedic abnormalities, and neurologic manifestations should be treated as in the general population.

• Education intervention, as indicated by evaluation and IEP (individual education plan).

Prevention of Secondary Complications

Routine pediatric immunizations should be given and administration of pneumococcal vaccination should be considered.

The combination of dilated cardiomyopathy, congestive heart failure, pulmonary hypertension, and pulmonary fibrosis can cause sudden severe hypoxia in a patient following surgery or even during a minor infection. Close monitoring of cardiac status and oxygenation are necessary until the patient is fully recovered.

Surveillance

Rod-cone dystrophy. Annual ophthalmologic follow-up is indicated as long as the affected individual has vision.

Obesity. Weight, height, and body mass index (BMI) should be recorded annually and plotted on growth curves.

Progressive sensorineural hearing loss. Audiometry should be performed yearly.

Cardiomyopathy

• A detailed cardiac history and examination including echocardiography annually even in the absence of symptoms related to left ventricular dysfunction (signs of cardiac failure, such as sweating, fatigue, lethargy, asthma, decreased physical activity)

• ECGs in parallel with echocardiography and 24-hour ECG monitoring if indicated

• In individuals who have had infantile cardiomyopathy, annual monitoring by a pediatric cardiologist, even if the individual has recovered from cardiomyopathy and is asymptomatic

Insulin resistance/type 2 diabetes

• Annual measurement of plasma insulin concentration, as hyperinsulinemia may be present from early infancy

• Measurement of fasting plasma glucose concentration every two to three months

• If fasting blood glucose is greater than 7 mmol/L, or postprandial blood glucose is greater than 11 mmol/L, measurement of HbA1c concentration and serum glucose concentration regularly (every 6 months, although glucose estimations may be performed more frequently as determined by the 'diabetic control' of the affected individual)

Hyperlipidemia. Annual total lipid profile determination is appropriate unless hyperlipidemia is present, in which case more frequent monitoring may be indicated. When the affected individual is ill and/or dehydrated, pancreatitis precipitated by hyperlipidemia can be life threatening.

Renal disease

• Urinalysis and measurement of plasma concentrations of electrolytes, uric acid, BUN, and creatinine twice yearly

• Renal and bladder ultrasound examinations every one to two years if the individual is symptomatic or if urinalysis is abnormal

Hepatic disease

• Annual measurement of plasma ALT, AST, and GGT concentration

• Ultrasonography to evaluate for possible steatosis, hepatomegaly, cirrhosis, and portal hypertension

Pulmonary disease. Pulmonary function tests should be performed yearly to evaluate general lung function, even if symptoms of pulmonary fibrosis are not yet present.

Hypothyroidism. Patients should be monitored annually for thyroid abnormalities.

Agents/Circumstances to Avoid

Any substance contraindicated in persons with renal or cardiac failure should be avoided.

Therapy directed at one system may have adverse effects on other systems; for example, the use of glitazone therapy in diabetes mellitus is contraindicated in the presence of cardiac failure.

Evaluation of Relatives at Risk

Early evaluation and/or molecular genetic testing (if the two disease-causing mutations in a family are known) of at-risk sibs allows early diagnosis and early treatment of manifestations.

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Therapies Under Investigation

Search ClinicalTrials.gov for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Registries

Contact information for voluntary patient registries is provided by GeneReviews staff.

Alstrom Syndrome Registry
Phone: 800-371-3628; 207-288-6385
Fax: 207-288-6078
Email: jan.marshall@jax.org
Web: www.alstrom.org

Other

Genetics clinics, staffed by genetics professionals, provide information for individuals and families regarding the natural history, treatment, mode of inheritance, and genetic risks to other family members as well as information about available consumer-oriented resources. See the GeneTests Clinic Directory.

See Consumer Resources for disease-specific and/or umbrella support organizations for this disorder. These organizations have been established for individuals and families to provide information, support, and contact with other affected individuals.

Mode of Inheritance

Alström syndrome is inherited in an autosomal recessive manner.

Risk to Family Members

Parents of a proband

• The parents of an affected individual are obligate heterozygotes and therefore carry one mutant allele.

• Heterozygotes (carriers) are asymptomatic.

Sibs of a proband

• At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.

• Once an at-risk sib is known to be unaffected, the chance of his/her being a carrier is 2/3.

Offspring of a proband. With very rare exceptions, individuals with Alström syndrome are not known to be fertile.

Other family members of a proband. Each sib of the proband's parents is at a 50% risk of being a carrier.

Carrier Detection

Carrier testing for at-risk family members is possible if the disease-causing mutations have been identified in a family member.

Related Genetic Counseling Issues

Family planning

• The optimal time for determination of genetic risk, clarification of carrier status, and discussion of the availability of prenatal testing is before pregnancy.

• It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers, or are at risk of being carriers.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, mutations, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals. See for a list of laboratories offering DNA banking.

Prenatal Testing

Prenatal diagnosis for pregnancies at increased risk is possible by analysis of DNA extracted from fetal cells obtained by amniocentesis usually performed at about 15 to 18 weeks' gestation or chorionic villus sampling (CVS) at about ten to 12 weeks' gestation. Both disease-causing alleles of an affected family member must be identified before prenatal testing can be performed.

Note: Gestational age is expressed in menstrual weeks calculated either from the first day of the last normal menstrual period or by ultrasound measurements.

Preimplantation genetic diagnosis (PGD) may be available for families in which the disease-causing mutation has been identified. For laboratories offering PGD, see .

Note: It is the policy of GeneReviews to include in GeneReviews™ chapters any clinical uses of testing available from laboratories listed in the GeneTests™ Laboratory Directory; inclusion does not necessarily reflect the endorsement of such uses by the author(s), editor(s), or reviewer(s).

Literature Cited

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Author History

Catherine Carey, MD, FRCP (2003-present)
Ian Hopkinson, BSc (Hons), MBChB, PhD, MRCGP; University College London (2003-2010)
Seamus Macdermott, MD, FRCS (2003-present)
Jan D Marshall, MS (2003-present)
Richard B Paisey, MD, FRCP (2005-present)

Revision History

• 8 June 2010 (me) Comprehensive update posted live

• 25 June 2007 (me) Comprehensive update posted to live Web site

• 7 February 2005 (me) Comprehensive update posted to live Web site

• 11 May 2004 (ih) Revision: test availability

• 7 February 2003 (me) Review posted to live Web site

• 6 June 2002 (ih) Original submission