Brain Behav. 2017 Dec 19;8(1):e00899. doi: 10.1002/brb3.899. eCollection 2018 Jan.
Familial multiple sclerosis and association with other autoimmune diseases.
Pytel V, Matías-Guiu JA, Torre-Fuentes L, Montero P, Gómez-Graña Á, García-Ramos R, Moreno-Ramos T, Oreja-Guevara C, Fernández-Arquero M, Gómez-Pinedo U, Matías-Guiu J.
Autoimmune diseases (AID) follow a complex, probably polygenic, pattern of inheritance and often cluster in families of patients with multiple sclerosis (MS). Our objective was to analyze family patterns and characteristics in families including more than one patient with MS.
Materials and Methods:
We analyzed personal and family history of neurological, systemic, and autoimmune diseases in 84 MS patients from 40 different families. Families were classified in two groups: families with cases of MS in at least two different generations (15 families) and families in which cases of MS belonged to only one generation (25 families).
The two previously established groups presented different clinical patterns and frequency of association with another AID. In one group, the second generation displayed a higher annual relapse rate than the first generation, higher frequency of progressive forms of MS, and more patients with another AID in addition to MS. Relapsing-remitting forms of MS (RRMS) were more frequent in the other group.
Families that include more than one MS patient may show two distinct patterns. This finding seems important for the compression and analysis of genetic information on MS.
Michael J Fox (who sadly has young-onset Parkinson’s disease) once said “family is not an important thing. It’s everything”. And many of you will agree that while the genetic legacy experiment has benefited some, it has wrongfully penalized others. Nevertheless, their importance cannot be discounted. To understand the what and whys of it may believe it or not provide the foundation for the development of a cure.
The inheritance of autoimmune disorders is complex and polygenic (more than one gene at play) characteristic, and more than one autoimmune disorder may exist in an individual with MS or in their family. The latter supports the theory that certain genetic traits may confer a predisposition to autoimmunity. If we take MS for instance, although, its cause is felt to be both genetic and environmental, the incidence is higher in twins, siblings and first degree relations (15-20% have a family relation with MS).
In this article, the authors look at the inheritance pattern of MS in families where there is more than one member affected and their association with other autoimmune disorders. In all, they looked at 40 families.
They found that in families with only one generation of MS were more likely to be relapsing-remitting MS (RRMS) than with families with two generations affected by MS and had a lower frequency of other autoimmune disorders. There was also a slight predisposition to maternal inheritance than a paternal line of inheritance. Maternal inheritance was also more likely to result in SPMS, particularly in those with two successive generations affected (although this association may be spurious). Families with both affected parents and children +/- affected uncles/aunts or grandparents demonstrated the anticipation phenomenon (i.e. presented earlier in children than in parents). It was also associated with increased severity in successive generations with significantly higher relapse rates (I have seen this in some of my patients).
Other autoimmune disorders also seem to gather in families and may have shared mechanisms. Here, they found that another autoimmune disorder occurred in ~24% of pwMS and 58% of families had a member with another autoimmune disorder. The most frequent autoimmune disorder association was not surprisingly thyroid disease. RRMS also tended to be more frequent in families with another autoimmune disorder.
This paper is clearly food for thought as far as inheritance patterns of autoimmune disorders is concerned. When it comes to diseases in families, recall bias is a definite concern and therefore more studies looking at this and linked MS databases for verification are definitely needed.