BACKGROUND: There has been no previous systematic study of conjugal multiple sclerosis. This study of conjugal pairs with complex traits investigated disease transmissibility and the genetic contribution to frequency and clinical course. METHODS: We studied 45 conjugal pairs concordant for multiple sclerosis from 58 pairs recorded in a national register of familial disease, 86 offspring of the 45 pairs were individually assessed for clinical evidence of neurological disease; those over age 16 underwent cranial magnetic resonance imaging. Clinical features were compared in 33 pairs in whom neither member had symptoms before they met. FINDINGS: Of the 86 offspring, five (6%) had clinically definite multiple sclerosis. A further five children had either characteristic imaging abnormalities or clinical symptoms consistent with demyelination, but did not meet the criteria for clinically definite disease. There was no evidence of clinical concordance, clustering at year of onset, or distortion of the expected pattern of age of onset in the second affected spouse from 33 pairs. The crude recurrence in children of conjugal pairs (1 in 17) is significantly higher than previously reported population-based risk for offspring of single affected parents (1 in 200). INTERPRETATION: Taken with the low prevalence of multiple sclerosis in the spouses of affected individuals, and the lack of concordance for age at onset in these families, the disparity in crude recurrence between children of conjugal pairs and those of single affected parents shows that the recurrence risk in children is determined by genetic factors inherited from both parents.
BACKGROUND: There has been no previous systematic study of conjugal multiple sclerosis. This study of conjugal pairs with complex traits investigated disease transmissibility and the genetic contribution to frequency and clinical course. METHODS: We studied 45 conjugal pairs concordant for multiple sclerosis from 58 pairs recorded in a national register of familial disease, 86 offspring of the 45 pairs were individually assessed for clinical evidence of neurological disease; those over age 16 underwent cranial magnetic resonance imaging. Clinical features were compared in 33 pairs in whom neither member had symptoms before they met. FINDINGS: Of the 86 offspring, five (6%) had clinically definite multiple sclerosis. A further five children had either characteristic imaging abnormalities or clinical symptoms consistent with demyelination, but did not meet the criteria for clinically definite disease. There was no evidence of clinical concordance, clustering at year of onset, or distortion of the expected pattern of age of onset in the second affected spouse from 33 pairs. The crude recurrence in children of conjugal pairs (1 in 17) is significantly higher than previously reported population-based risk for offspring of single affected parents (1 in 200). INTERPRETATION: Taken with the low prevalence of multiple sclerosis in the spouses of affected individuals, and the lack of concordance for age at onset in these families, the disparity in crude recurrence between children of conjugal pairs and those of single affected parents shows that the recurrence risk in children is determined by genetic factors inherited from both parents.
Authors: Stephen Sawcer; Maria Ban; Mel Maranian; Tai Wai Yeo; Alastair Compston; Andrew Kirby; Mark J Daly; Philip L De Jager; Emily Walsh; Eric S Lander; John D Rioux; David A Hafler; Adrian Ivinson; Jacqueline Rimmler; Simon G Gregory; Silke Schmidt; Margaret A Pericak-Vance; Eva Akesson; Jan Hillert; Pameli Datta; Annette Oturai; Lars P Ryder; Hanne F Harbo; Anne Spurkland; Kjell-Morten Myhr; Mikko Laaksonen; David Booth; Robert Heard; Graeme Stewart; Robin Lincoln; Lisa F Barcellos; Stephen L Hauser; Jorge R Oksenberg; Shannon J Kenealy; Jonathan L Haines Journal: Am J Hum Genet Date: 2005-07-29 Impact factor: 11.025
Authors: J Chataway; A Mander; N Robertson; S Sawcer; J Deans; M Fraser; S Broadley; D Clayton; A Compston Journal: J Neurol Neurosurg Psychiatry Date: 2001-12 Impact factor: 10.154
Authors: D R Booth; A T Arthur; S M Teutsch; C Bye; J Rubio; P J Armati; J D Pollard; R N S Heard; G J Stewart Journal: J Mol Med (Berl) Date: 2005-08-02 Impact factor: 4.599