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| {{SK}} Alstrom-Hallgren syndrome; ALMS; ALSS | | {{SK}} Alstrom-Hallgren syndrome; ALMS; ALSS |
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| ==Overview== | | ==[[Alstrom syndrome overview|Overview]]== |
| Alström syndrome is a rare genetic disorder caused by mutations in the gene ALMS1 which is located on the chromosome 2. It is among the rarest genetic disorders.
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| ==Historical Perspective== | | ==[[Alstrom syndrome historical perspective|Historical Perspective]]== |
| It was first described by [[Carl-Henry Alström]] in Sweden in 1959.
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| ==Epidemiology and Demographics== | | ==[[Alstrom syndrome pathophysiology|Pathophysiology]]== |
| It is among the rarest genetic disorders in the world, as currently it has only 266 reported cases in medical literature and only 800 known cases in 54 countries.
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| ==Pathophysiology== | | ==[[Alstrom syndrome differential diagnosis|Differentiating Alstrom syndrome from other Diseases]]== |
| The Jackson Laboratory in Bar Harbor, Maine, USA with the [[University of Southampton]], UK isolated the single [[gene]] ([[ALMS1]]) responsible for Alstrőm Syndrome. The gene is [[recessive]]; it must be passed from both parents for the syndrome to manifest.
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| The key features are childhood obesity, blindness due to congenital cone-rod retinal [[dystrophy]], and [[sensorineural hearing loss]]. Associated [[endocrinology|endocrinologic]] features include [[hyperinsulinemia]], early-onset [[type 2 diabetes]], and [[hypertriglyceridemia]]. Thus, AS shares several features with the common metabolic syndrome, namely [[obesity]], [[hyperinsulinemia]], and [[hypertriglyceridemia]]. Mutations in the [[ALMS1]] gene have been found to be causative for AS with a total of 79 disease-causing mutations having been described.<ref name="pmid18154657">{{cite journal | author=Joy T, Cao H, Black G, Malik R, Charlton-Menys V, Hegele RA, Durrington PN |title=Alstrom syndrome (OMIM 203800): a case report and literature review. | journal=Orphanet Journal of Rare Diseases | year=2007 | volume=2 | issue=1 | pmid = 18154657 | url=http://www.ojrd.com/content/pdf/1750-1172-2-49.pdf | pmc=2266715 | doi=10.1186/1750-1172-2-49 |pages=49}}</ref>
| | ==[[Alstrom syndrome epidemiology and demographics|Epidemiology and Demographics]]== |
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| The cone-rod retinal dystrophy usually develops within the first few weeks after birth and the symptoms include [[nystagmus]] and extreme photodysphoria (light sensitivity). It is progressive and by the second decade of life leads to blindness. Most patients slowly develop bilateral sensorineural hearing loss. [[Dilated cardiomyopathy]] can develop at any age (infants or adolescents). It is seen in at least two-thirds of the patients and can lead to sudden [[cardiac failure]].
| | ==[[Alstrom syndrome risk factors|Risk Factors]]== |
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| ===Genetics===
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| ALMS1 encodes a protein whose function is unknown. Mutations in this gene can lead to production of a dysfunctional protein that might be responsible for the signs and symptoms of Alstrom disease. Alström syndrome (AS) is a rare [[autosomal]] recessive disease characterized by multiorgan dysfunction.
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| ==Differentiating Alstrom syndrome from other Diseases==
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| Alstrom syndrome is sometimes confused with [[Bardet-Biedl syndrome]], which has similar symptoms. Bardet-Biedl syndrome tends to have later onset in its symptoms. Alstrom syndrome is a ciliopathy. Other ciliopathies that should be differentiated from Alstrom syndrome include:
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| * [[Primary ciliary dyskinesia]]
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| * [[Polycystic kidney disease]]
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| * [[Polycystic liver disease]]
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| * [[Nephronophthisis]]
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| * [[Meckel-Gruber syndrome]]
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| * Biemond II syndrome
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| * [[Wolfram syndrome]]
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| * [[Cohen syndrome]]
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| * Sporadic infantile DCM
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| * Mitochondrial disorders
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| * Some forms of [[retinal degeneration]]<ref>{{cite journal
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| | last = Badano
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| | first = Jose L.
| | ==[[Alstrom syndrome screening|Screening]]== |
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| | ==[[Alstrom syndrome natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
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| | coauthors = Norimasa Mitsuma, Phil L. Beales, Nicholas Katsanis
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| | title = The Ciliopathies : An Emerging Class of Human Genetic Disorders
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| | journal = Annual Review of Genomics and Human Genetics
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| | volume = 7
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| | issue =
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| | pages = 125–148
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| | publisher =
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| | location =
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| | date = September 2006
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| | pmid = 16722803
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| | url = http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.genom.7.080505.115610
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| | doi = 10.1146/annurev.genom.7.080505.115610
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| | id =
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| | accessdate = 2008-06-15}}</ref>
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| ==Diagnosis== | | ==Diagnosis== |
| It is possible to clinically detect Alström syndrome in infancy, but more frequently, it is detected much later, as doctors tend to detect symptoms as separate problems. Currently, Alström syndrome is only diagnosed clinically, since [[genetic testing]] is still rare and only available on a limited basis.
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| ===Diagnostic Criteria===
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| Marshall JD et al. provided a comprehensive guidance for diagnostic criteria in their 2007 publication.
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| '''Birth - 2 years:'''
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| Minimum diagnosis requires 2 major criteria or 1 major and 2 minor criteria.
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| Major criteria are:
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| 1) [[ALMS1]] [[mutatio]]n in 1 [[allele]] and/or family history of Alström Syndrome
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| 2) Vision pathology ([[nystagmus]], [[photophobia]])
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| Minor criteria are:
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| 1) [[Obesity]]
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| 2) [[Dilated cardiomyopathy]] with [[congestive heart failure]]
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| Other variable supportive evidence:
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| Recurrent pulmonary infections, normal digits, delayed developmental milestones.
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| '''At 3-14 years of age:'''
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| 2 major criteria or 1 major and 3 minor criteria.
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| Major criteria are:
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| 1) ALMS1 mutation in 1 allele and/or family history of Alström Syndrome,
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| 2) Vision pathology (nystagmus, photophobia, diminished acuity). If old enough for testing: cone dystrophy by electroretinography (ERG).
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| Minor Criteria:
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| 1) Obesity and/or insulin resistance and/or Type 2 Diabetes
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| 2) History of dilated cardiomyopathy with congestive heart failure
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| 3) Hearing loss
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| 4) Hepatic dysfunction
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| 5) Renal failure
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| 6) Advanced bone age
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| Variable supportive evidence:
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| Recurrent pulmonary infections, normal digits, delayed developmental milestones, hyperlipidemia, scoliosis, flat wide feet,hypothyroidism, hypertension, recurrent urinary tract infection, growth hormone deficiency.
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| '''Presentation 15 years - adulthood:'''
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| 2 major and 2 minor criteria or 1 major and 4 minor criteria.
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| Major criteria are:
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| 1) ALMS1 mutation in 1 allele and/or family history of Alström Syndrome.
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| 2) Vision pathology (history of nystagmus in infancy/childhood, legal blindness, cone and rod dystrophy by ERG).
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| Minor criteria:
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| 1) Obesity and/or insulin resistance and/or Type 2 Diabetes
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| 2) History of dilated cardiomyopathy with congestive heart failure.
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| 3) Hearing loss
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| 4) Hepatic dysfunction
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| 5) Renal failure
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| 6) Short stature
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| 7) Males: hypogonadism, Females: irregular menses and/or hyperandrogenism
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| Other supportive features:
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| Recurrent pulmonary infections, normal digits, history of developmental delay, hyperlipidemia, scoliosis, flat wide feet, hypothyroidism, hypertension, recurrent urinary tract infections/urinary dysfunction, growth hormone deficiency, alopecia.
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| ===Symptoms===
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| ====Early Symptoms====
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| *[[Heart failure]] (Dilated [[cardiomyopathy]]) in over 60% of cases, usually within the first few weeks after birth, but sometimes the onset is in adolescence or adulthood.
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| *[[Light sensitivity]] and vision problems ([[Cone-rod dystrophy]]) in all cases, usually within 15 months of birth and progressively worsening until about 20 years of age
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| *[[Developmental delays]] in 50% of cases, [[learning disabilities]] in about 30% of cases
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| *[[Obesity]] in 100% of cases, apparent by 5 years of age, but often apparent in infancy (Alström infants usually have normal birth weights, and by adolescence, weights tend to be in the high-normal to normal range)
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| ====Later Symptoms====
| | [[Alstrom syndrome diagnostic criteria|Diagnostic Criteria]] | [[Alstrom syndrome history and symptoms|History and Symptoms ]] | [[ Alstrom syndrome physical examination|Physical Examination]] | [[Alstrom syndrome laboratory findings|Laboratory Findings]] | [[Alstrom syndrome electrocardiogram|Electrocardiogram]] | [[Alstrom syndrome chest x ray|Chest X Ray]] | [[Alstrom syndrome CT|CT]] | [[Alstrom syndrome MRI|MRI]] | [[Alstrom syndrome echocardiography or ultrasound|Echocardiography or Ultrasound]] | [[Alstrom syndrome other imaging findings|Other Imaging Findings]] | [[Alstrom syndrome other diagnostic studies|Other Diagnostic Studies]] |
| *Progressive [[hearing loss]]
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| *[[Kidney problems]]
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| *Liver problems
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| *[[Insulin resistance]]/[[Type 2 diabetes]]
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| ===Physical Examination===
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| ====Appearance of the Patient====
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| Patients have distinctive facial characteristics (deep-set eyes with a rounded face, thick ears, premature frontal balding, and thin hair).
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| ====Extremities==== | | ==Treatment== |
| Wide, thick, flat feet, and short stubby fingers and toes
| | [[Alstrom syndrome medical therapy|Medical Therapy]] | [[Alstrom syndrome surgery |Surgery]] | [[Alstrom syndrome primary prevention|Primary Prevention]] | [[Alstrom syndrome secondary prevention|Secondary Prevention]] | [[Alstrom syndrome cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Alstrom syndrome future or investigational therapies|Future or Investigational Therapies]] |
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| ==References== | | ==Case Studies== |
| {{Reflist|2}}
| | [[Alstrom syndrome case study one|Case #1]] |
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| ==External Links== | | ==External Links== |