Spinal Muscular Atrophy Genetic Counseling Access and Genetic Knowledge: Parents' Perspectives

Abstract

Spinal muscular atrophy is characterized by degeneration of α motor neurons in the anterior horns of the spinal cord, which leads to progressive symmetrical muscle weakness and atrophy. Spinal muscular atrophy is the leading fatal autosomal recessive disorder in infancy, and genetic counseling is an essential component of the care of families of these patients. However, little guidance is available in the published literature regarding the process and benefit of genetic counseling for families. Accordingly, the authors designed a questionnaire to assess parents' knowledge of the disease, gauge their access to genetic counseling, and determine how parents use information gained from counseling to guide choices for future pregnancies. The questionnaire specifically targeted when genetic counseling was received, from whom, parental knowledge regarding spinal muscular atrophy genetics, parental choices regarding spinal muscular atrophy and their child, frequency of prenatal testing, perceived relevance of newborn screening, and opinions regarding the disease. Most families clearly received some type of genetic counseling. Yet how and from whom they received the information varied greatly, as did their genetic knowledge of spinal muscular atrophy. The highest percentage of families received counseling from neurologists, who may not be appropriately prepared to provide formal genetic counseling. Many respondents reported having a negative experience with genetic counseling, possibly because it occurred at the time of diagnosis or shortly afterward, a period of great emotional turmoil. These data suggest that a consistent approach for facilitating how and when genetic counseling is received is greatly needed. Keywordsspinal muscular atrophy; genetic counseling; genetic testing; carrier testing; parents' perspectives Spinal muscular atrophy is caused by a deletion or mutation in the survival motor neuron 1 (SMN1)gene. SMN1 was discovered in 1995 and is located on chromosome 5q11-q13. 1 SMN1 contains 9 exons that encode a 294 amino acid protein. Spinal muscular atrophy is characterized by degeneration of α motor neurons in the anterior horns of the spinal cord, which leads to progressive symmetrical muscle weakness and atrophy. It affects approximately 1 in 6000 to 10 000 white newborns and previously was the second most common fatal autosomal recessive disorder after cystic fibrosis. 7 Advances in the treatment of cystic fibrosis have resulted in a marked decrease in childhood mortality in that disorder, such that spinal muscular atrophy is now the leading fatal autosomal recessive disorder of infancy. Spinal muscular atrophy is clinically subdivided into 3 types. 8 Type 1 (Werdnig-Hoffmann) is characterized by muscle weakness prior to 6 months of age. Affected infants are unable to sit without support. Spinal muscular atrophy type 1 infants account for 60% to 70% of cases. Prognosis is grave, with most not surviving beyond their second birthday without substantial respiratory support. 9 Type 2 is characterized ...

Carrier testing in children: exploration of genetic health professionals’ practices in Australia

“…[1][2][3][4]10,30 The finding that some parents persist with requests and receive testing is important because previous studies have not distinguished between carrier testing driven by parental requests and medical recommendations. 22,31,32 This study identified surprising differences in the reported frequency of parental requests for carrier testing in their children. The interview process uncovered variation in what counts as a request for testing, with one interpretation being that a simple expression of interest constitutes a request and another being that only a more formal and specific request for carrier testing does so.…”

An Ashkenazi Jewish SMN1 haplotype specific to duplication alleles improves pan-ethnic carrier screening for spinal muscular atrophy

“…1 The disease is characterized by the progressive degeneration and loss of anterior horn cells in the spinal cord and brainstem nuclei causing symmetric muscle weakness and atrophy, 2,3 and the clinical subtypes (I-IV) are primarily based on age at onset and disease severity.…”

Parents’ experiences with requesting carrier testing for their unaffected children

“…9,12 In some cases, carrier testing is carried out for the sibling of an affected child despite the recommendations. 1,[13][14][15][16][17][18][19] Studies reporting carrier-testing practices of health professionals indicate that genetic health professionals are willing to facilitate carrier testing for autosomal recessive and X-linked conditions in unaffected children to varying degrees. [13][14][15][16]20 For example, in an interview-based study of 17 key informant genetic health professionals in Australia, we found that all our participants initially recommended against carrier testing in children following parental requests, with some preemptively discussing it as a test they generally do not perform.…”