Familial variable expression of dilated cardiomyopathy in Alström syndrome: A report of four sibs

Hoffman, Jodi D.; Jacobson, Z.; Young, Terri L.; Marshall, Jan D.; Kaplan, Paige

doi:10.1002/ajmg.a.30688

Cited by 33 publications

(29 citation statements)

References 4 publications

(6 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Three siblings presented with infantile DCM, two of them resolved completely, one displayed near full recovery but later experienced some deterioration in his cardiac function. The fourth sibling experienced the most severe course, culminating in end stage heart failure following an unsuccessful heart transplantation [6]. Our report further emphasizes this familial variability, both in the course and prognosis of cardiac disease.…”

Section: Discussionsupporting

confidence: 53%

Extreme Clinical Variability of Dilated Cardiomyopathy in Two Siblings With Alström Syndrome

Mahamid¹,

Lorber

Horovitz

et al. 2012

Pediatr Cardiol

View full text Add to dashboard Cite

Alström syndrome (ALMS) is a rare autosomal recessive disorder caused by mutations in the ALMS1 gene. We report on two brothers, 2 and 3 years of age, diagnosed with Alström syndrome who initially presented in infancy with severe dilated cardiomyopathy during febrile respiratory infection. The disease course in the two siblings was marked by significant intra-familial variability. While cardiomyopathy in the older sibling has mainly resolved allowing for the discontinuation of medical therapy, heart function in the younger sibling continues to deteriorate despite maximal drug support with furosemide, carvedilol, captopril and aldospirone. Genetic analysis revealed homozygous mutations, c.8008C>T (R2670X), in ALMS1 resulting in premature protein truncation. This report further emphasizes the exceptional intra-familial variability of ALMS, mainly in the natural course of cardiac disease.

show abstract

Section: Discussionsupporting

confidence: 53%

Extreme Clinical Variability of Dilated Cardiomyopathy in Two Siblings With Alström Syndrome

Mahamid¹,

Lorber

Horovitz

et al. 2012

Pediatr Cardiol

View full text Add to dashboard Cite

show abstract

“…Many recover low-normal cardiac function for many years while on medical therapy, yet DCM may suddenly recur with rapid progression and poor clinical outcome [Marshall et al, 2007, Marshall et al, 2011]. While recognition of Alström syndrome is usually delayed or possibly missed owing to its rarity and age-dependent expression of pleiotropic clinical features [Hoffman et al, 2005], the use of whole exome sequencing in our patient enabled a pre-emptive diagnosis of Alström syndrome and establishment of the etiology for heart failure. Moreover, a definitive diagnosis is guiding clinical monitoring for extra-cardiac manifestations of the disorder [Monitoring guidelines, Alström syndrome international website] and facilitating early intervention planning, such as enrollment in a specialty school for the blind for inevitable visual loss and dietary counseling to mitigate obesity [Lee et al, 2009].…”

Section: Discussionmentioning

confidence: 99%

Exome sequencing establishes diagnosis of Alström syndrome in an infant presenting with non‐syndromic dilated cardiomyopathy

Long

Evans

Olson

2015

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Idiopathic dilated cardiomyopathy is a heritable, genetically heterogeneous disorder characterized by progressive heart failure. Dilated cardiomyopathy typically exhibits autosomal dominant inheritance, yet frequently remains clinically silent until adulthood. We sought to discover the molecular basis of idiopathic, non-syndromic dilated cardiomyopathy in a one-month-old male presenting with severe heart failure. Previous comprehensive testing of blood, urine, and skin biopsy specimen was negative for metabolic, mitochondrial, storage, and infectious etiologies. Ophthalmologic examination was normal. Chromosomal microarray and commercial dilated cardiomyopathy gene panel testing failed to identify a causative mutation. Parental screening echocardiograms revealed no evidence of clinically silent dilated cardiomyopathy. Whole exome sequencing was carried out on the family trio on a research basis, filtering for rare, deleterious, recessive and de novo genetic variants. Pathogenic compound heterozygous truncating mutations were identified in ALMS1, diagnostic of Alström syndrome and prompting disclosure of genetic findings. Alström syndrome is a known cause for dilated cardiomyopathy in children yet delayed and mis-diagnosis are common owing to its rarity and age-dependent emergence of multisystem clinical manifestations. At six months of age the patient ultimately developed bilateral nystagmus and hyperopia, features characteristic of the syndrome. Early diagnosis is guiding clinical monitoring of other organ systems and allowing for presymptomatic intervention. Furthermore, recognition of recessive inheritance as the mechanism for sporadic disease has informed family planning. This case highlights a limitation of standard gene testing panels for pediatric dilated cardiomyopathy and exemplifies the potential for whole exome sequencing to solve a diagnostic dilemma and enable personalized care.

show abstract

“…The age of onset extended from infancy to adult life. Considerable familial variability in the degree of dilated cardiomyopathy was observed by Hoffman et al 9 Cardiac insufficiency represented a significant factor in early death. In another report, cardiac failure developed in 18 of 22 individuals between 2 weeks and 7 months of age; notably, a 16-year-old in this cohort suffered a delayed onset by comparison with the majority of subjects.…”

Section: In 2005mentioning

confidence: 95%

Alström Syndrome: Progressive Deafness and Blindness

Welsh¹

2007

Ann Otol Rhinol Laryngol

View full text Add to dashboard Cite

Alström syndrome is a very rare, genetically transmitted disorder that affects special sense functions, resulting in progressive visual and auditory impairment. The diagnostic criteria for this disorder are presented, and the differential issues between it and other, similar syndromal forms of sensory and multisystem dysfunction are discussed. A report of 2 siblings so involved is summarized. The disability of other organs is considered, namely, the kidney, the heart, and the metabolic and endocrine systems.

show abstract

Familial variable expression of dilated cardiomyopathy in Alström syndrome: A report of four sibs

Cited by 33 publications

References 4 publications

Extreme Clinical Variability of Dilated Cardiomyopathy in Two Siblings With Alström Syndrome

Extreme Clinical Variability of Dilated Cardiomyopathy in Two Siblings With Alström Syndrome

Exome sequencing establishes diagnosis of Alström syndrome in an infant presenting with non‐syndromic dilated cardiomyopathy

Alström Syndrome: Progressive Deafness and Blindness

Contact Info

Product

Resources

About