Tuesday, 27 March 2018

Familial MS

Keeping it in the family.




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.

Objectives:

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).

Results:

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.

Conclusions:

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.

14 comments:

  1. These results confirm what I already know, what I've seen, within the family

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  2. You are so clever ndg. What trial are you going to be leading?

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    1. Can't wait- you are a hero to female, bame and LGBT scientists

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  3. I too have a family history of MS, but how do we remove the impact of MS from the figures? Having a parent with MS restricts development, my siblings and I spent more time inside, we didn’t travel or go on vacations (to the sun). That must have had an impact.

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    1. Yes, these are the confounders. It is often the series of events which lead to the condition, but there does seem to be an anticipation phenomenon which seems to come through as well.

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  4. This is interesting because I have 0 family or even extended family with MS...no one including myself even knew what it meant when I got diagnosed

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    1. The Ebers group looked for differences between sporadic MS and familial MS previous and did not find any difference between the two in terms of demographics and clinical features.

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  5. My mother, mother-in law, and I all have RRMS (I'm a woman). Neither I nor my mother had been diagnosed when my partner and I met; it all happened in the last 1.5 years. With MS on both the maternal and paternal side, can you speculate on our future children's likelihood of having MS one day, or at least confirm that the risk is likely to be increased?

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    1. I wandered when someone would ask this question. I don’t think the answer is really known about the exact risks. Jan Hillerts group reported a while back using a large Swedish registry stating that familial risks may be lower than usually reported (heritability was estimated to be 0.64, and shared environmental component to be 0.01). They also didn’t find any difference between paternal and maternal relations, although there was a greater chance of transmission from father to son, than mother to son (I.e higher rate of transmission from the less prevalent gender for MS). All of this is possible with the retro scope but you can’t use these figures to council individual families about their genetic risk. It is less ambiguous when you’re dealing with twins and one has MS.

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  6. I have MS and am the "first" generation to have MS throughout my maternal and paternal family. But I have a sister who has also developed an autoimmunity, for thyroid, she has hypothyroidism.

    Is there any study, a global consortium of DNA analysis, that encompasses third world countries?

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    1. Not that I'm aware of, or databases beyond what the Multiple Sclerosis Federation has performed to obtain incidence figures.

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  7. My father has PPMS. I have SLE and AI Vasculitis.

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  8. The HERV theory could maybe explain the familial autoimmunity better as well as the paternal-maternal difference (I think it is more difficult for HERVs to infect sperm ).+EBV as a trigger.
    I fall in to category maternal thyroid (Hash), me MS.

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