An infant with hypoplastic left heart syndrome and spinal muscular atrophy

Cook, Amanda L.; Curzon, Christopher L.; Milazzo, A

doi:10.1017/s1047951105002131

Cited by 10 publications

(1 citation statement)

References 10 publications

(12 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These systemic defects must be described and understood before effective therapies can be designed. Significantly, there is considerable evidence of circulatory system defects in animal models and SMA patients, with reports of defects in heart morphology 8 9 10 11 12 13 14 15 16 17 18 19 and function 20 21 22 23 24 25 26 . In addition, there is a growing body of evidence to support a wide range of defects affecting the structural and circulating component of the vascular system: capillaries are depleted in muscle and spinal cord 27 28 , resulting in significant tissue hypoxia 28 ; red and white cell counts are altered 29 , blood clots are present 30 , anti-coagulation therapy resolves digital necrosis 30 31 ; SMN protein is enriched in anuclear platelets 32 and platelet numbers are altered by therapeutic interventions in SMA 29 .…”

mentioning

confidence: 99%

Survival Motor Neuron (SMN) protein is required for normal mouse liver development

Szunyogova

Zhou

Maxwell

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Spinal Muscular Atrophy (SMA) is caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene. Decreased levels of, cell-ubiquitous, SMN protein is associated with a range of systemic pathologies reported in severe patients. Despite high levels of SMN protein in normal liver, there is no comprehensive study of liver pathology in SMA. We describe failed liver development in response to reduced SMN levels, in a mouse model of severe SMA. The SMA liver is dark red, small and has: iron deposition; immature sinusoids congested with blood; persistent erythropoietic elements and increased immature red blood cells; increased and persistent megakaryocytes which release high levels of platelets found as clot-like accumulations in the heart. Myelopoiesis in contrast, was unaffected. Further analysis revealed significant molecular changes in SMA liver, consistent with the morphological findings. Antisense treatment from birth with PMO25, increased lifespan and ameliorated all morphological defects in liver by postnatal day 21. Defects in the liver are evident at birth, prior to motor system pathology, and impair essential liver function in SMA. Liver is a key recipient of SMA therapies, and systemically delivered antisense treatment, completely rescued liver pathology. Liver therefore, represents an important therapeutic target in SMA.

show abstract

mentioning

confidence: 99%

Survival Motor Neuron (SMN) protein is required for normal mouse liver development

Szunyogova

Zhou

Maxwell

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

Congenital heart defects in spinal muscular atrophy type I: A clinical report of two siblings and a review of the literature

Menke

Poll-Thé

Clur

et al. 2008

American J of Med Genetics Pt A

View full text Add to dashboard Cite

A newborn girl presented with asphyxia, joint contractures and diminished spontaneous movements. Echocardiography showed hypoplastic left heart. Spinal muscular atrophy type I (SMA I) was diagnosed by detecting a homozygous deletion in the survival motor neuron 1 gene (SMN1). In the first trimester of a subsequent pregnancy, SMA I, hypoplastic left heart, and contractures were identified again. Congenital heart defects (CHD) have now been reported in 20 patients with SMA I, including three previously reported siblings and our two siblings, leading us to hypothesize that SMA I/CHD represents a unique phenotype of SMA I rather than a coincidental association. The homozygous SMN1 deletion may play a role in the development of CHD when it occurs in the presence of mutations or polymorphisms in other genes important for cardiac development.

show abstract

Cardiological Aspects of Systemic Disease

English¹,

Ettedgui²

2010

Paediatric Cardiology

View full text Add to dashboard Cite

An infant with hypoplastic left heart syndrome and spinal muscular atrophy

Cited by 10 publications

References 10 publications

Survival Motor Neuron (SMN) protein is required for normal mouse liver development

Survival Motor Neuron (SMN) protein is required for normal mouse liver development

Congenital heart defects in spinal muscular atrophy type I: A clinical report of two siblings and a review of the literature

Cardiological Aspects of Systemic Disease

Contact Info

Product

Resources

About