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Genotype-phenotype studies in infantile spinal muscular atrophy (SMA) type I in Germany: implications for clinical trials and genetic counselling.
Clin Genet 2009; 76(2):168-78CG

Abstract

We reviewed the natural history and assessed the SMN2 copy number of 66 patients with infantile spinal muscular atrophy (SMA) type I born between 2000 and 2005 in Germany whose diagnosis was confirmed by a homozygous SMN1 deletion in the first 6 months of life. After excluding patients who had received valproic acid, the median/mean age at disease endpoint was 6.1/7.3 months (range 0.0-34.0). Four (6.1%) patients with one SMN2 copy had severe SMA type '0' with joint contractures and respiratory distress from birth. Median/mean age at onset (months) in 57 (86.3%) patients with two SMN2 copies was 1.2/1.3, and 3.5/3.4 in 5 (7.6%) patients with three SMN2 copies. Median/mean age at disease endpoint was 6.5/7.8 months (range 0.5-30) in patients with two SMN2 copies. All patients with three SMN2 copies were still alive at 10-55 months, two of them under permanent ventilation. Our data are relevant for prognostication and genetic counselling. The observed clinical variability, especially in the group with two SMN2 copies, might be important for clinical trials in SMA I where a possible control group could be defined as follows: age at onset within 4-5 months, age at genetic diagnosis <6 months, two SMN2 copies present, head control in less than 10%, no respiratory distress from birth, disease endpoint either age at death or age at permanent ventilation.

Authors+Show Affiliations

Institute of Human Genetics, RWTH Aachen University, Aachen, Germany. srudnik-schoeneborn@ukaachen.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19780763

Citation

Rudnik-Schöneborn, S, et al. "Genotype-phenotype Studies in Infantile Spinal Muscular Atrophy (SMA) Type I in Germany: Implications for Clinical Trials and Genetic Counselling." Clinical Genetics, vol. 76, no. 2, 2009, pp. 168-78.
Rudnik-Schöneborn S, Berg C, Zerres K, et al. Genotype-phenotype studies in infantile spinal muscular atrophy (SMA) type I in Germany: implications for clinical trials and genetic counselling. Clin Genet. 2009;76(2):168-78.
Rudnik-Schöneborn, S., Berg, C., Zerres, K., Betzler, C., Grimm, T., Eggermann, T., ... Heller, R. (2009). Genotype-phenotype studies in infantile spinal muscular atrophy (SMA) type I in Germany: implications for clinical trials and genetic counselling. Clinical Genetics, 76(2), pp. 168-78. doi:10.1111/j.1399-0004.2009.01200.x.
Rudnik-Schöneborn S, et al. Genotype-phenotype Studies in Infantile Spinal Muscular Atrophy (SMA) Type I in Germany: Implications for Clinical Trials and Genetic Counselling. Clin Genet. 2009;76(2):168-78. PubMed PMID: 19780763.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genotype-phenotype studies in infantile spinal muscular atrophy (SMA) type I in Germany: implications for clinical trials and genetic counselling. AU - Rudnik-Schöneborn,S, AU - Berg,C, AU - Zerres,K, AU - Betzler,C, AU - Grimm,T, AU - Eggermann,T, AU - Eggermann,K, AU - Wirth,R, AU - Wirth,B, AU - Heller,R, PY - 2009/9/29/entrez PY - 2009/9/29/pubmed PY - 2009/12/16/medline SP - 168 EP - 78 JF - Clinical genetics JO - Clin. Genet. VL - 76 IS - 2 N2 - We reviewed the natural history and assessed the SMN2 copy number of 66 patients with infantile spinal muscular atrophy (SMA) type I born between 2000 and 2005 in Germany whose diagnosis was confirmed by a homozygous SMN1 deletion in the first 6 months of life. After excluding patients who had received valproic acid, the median/mean age at disease endpoint was 6.1/7.3 months (range 0.0-34.0). Four (6.1%) patients with one SMN2 copy had severe SMA type '0' with joint contractures and respiratory distress from birth. Median/mean age at onset (months) in 57 (86.3%) patients with two SMN2 copies was 1.2/1.3, and 3.5/3.4 in 5 (7.6%) patients with three SMN2 copies. Median/mean age at disease endpoint was 6.5/7.8 months (range 0.5-30) in patients with two SMN2 copies. All patients with three SMN2 copies were still alive at 10-55 months, two of them under permanent ventilation. Our data are relevant for prognostication and genetic counselling. The observed clinical variability, especially in the group with two SMN2 copies, might be important for clinical trials in SMA I where a possible control group could be defined as follows: age at onset within 4-5 months, age at genetic diagnosis <6 months, two SMN2 copies present, head control in less than 10%, no respiratory distress from birth, disease endpoint either age at death or age at permanent ventilation. SN - 1399-0004 UR - https://www.unboundmedicine.com/medline/citation/19780763/Genotype_phenotype_studies_in_infantile_spinal_muscular_atrophy__SMA__type_I_in_Germany:_implications_for_clinical_trials_and_genetic_counselling_ L2 - https://doi.org/10.1111/j.1399-0004.2009.01200.x DB - PRIME DP - Unbound Medicine ER -