Can ALS skip a generation?

sparrowking

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Hi everyone,

We have a rather peculiar case with ALS or of type. My father started showing ALS symptoms about 5.5 years ago with foot drop and weakness of left great toe. His symptoms were consistent with ALS but some doctors were hesitant to diagnose him with ALS for whatever reason I don't understand (3 years ago, it was written as "demyelinating disorder or mitochondrial disorder" in his diagnosis and treated with cyclophosphamide for which my father's body responded initially and then it didn't after that). Other doctor's diagnosed him directly with MND after some few tests.

It all started with left leg and then right leg and then gradually progressed to hands and now he has difficulty swallowing and speaking. We will see a neurologist in next few weeks who said in our last appointment that he'll say whether it is a type of ALS or not. My father has 5 siblings of which youngest sibling died long back of something that seems ALS (don't know details exactly, it was very long back, she was in her 20's, became serious after her delivery and then died around 9 months later, if I'm not wrong). Another sibling, a male this time, died at around 52 with something close to ALS (some muscle disorder or paralysis, details are not clear). My grandfather and grandmother, on the other hand, lived a relatively long life, died in their mid 70's or close to 80's. However, I am sure they didn't die of ALS or such related disease since they were healthy, walking & talking and they died of some heart trouble or something, all of sudden (in a night). But my grandfather and grandmother were very closely related (Consanguine marriage - happens often in India). After my father's condition and with one reputed doctor diagnosing him with MND, my and my sister started worrying about whether we'll inherit the mutation.

My query being, whether it is possible for ALS to skip generation, as it didn't come to our grandparents, but three of their children (of 5) got it? Although, we are not sure of the diagnosis of those passed away (but were told of involvement with nerves). Also, is it possible that the conditions of my father and his two siblings is because of "Consanguine marriage", just want to know if there are any such conditions that mimic ALS very closely?

Each and every twitch in my leg started to worry me and I started to check on my left toe (that's how it started for my father) and has been checking on it constantly for past 8 months (from when I had knee problem). I started my PhD in January and it has been very stressful and am finding it very hard to concentrate with what's going with my father and twitches in my left leg (in calf, in thigh, above and around knee, foot, sometimes vibrating sensation in foot and toes; only sometimes not continuously). I had problem with my left Knee, as MRI showed some sort of mild degenerative meniscus tear, but moved to another country from then and couldn't get the treatment for that yet.

Any reply would be of great help and will be obliged.

Thank you for your time.
 

Nikki J

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This all seems terribly vague to be deciding everyone had ALS. You may be looking at some recessive neurologic disorder where your grandparents were both carriers and 3 of their children inherited whatever from both sides. If that is the case then it would only affect your generation if your mother was also a carrier and you got her mutated copy instead of her healthy one.

recessive FALS is exceedingly rare. I think there are only 1 or 2 mutations and they are , as I said very very rare.
there are other neurologic diseases ( SMA and HSP being two) that are more commonly recessive
 

sparrowking

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Thank you very much. My mother is altogether from a different family. How close are SMA and HSP or similar other recessive neurological disorders in mimicking ALS (since the symptoms and progression for my father are very much consistent with that of typical ALS)?
 

lgelb

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There are similarities but testing would have revealed key differences. SMA is mostly diagnosed in childhood or at most young adults, and most forms are not fatal. HSP likewise is not a disease found after midlife as most ALS is and has different features, and a much slower progression than ALS. You can find full descriptions easily to see what if anything might fit.
 

sparrowking

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Thanks a lot for the replies. SMA and HSP doesn't both seem to fit what my father is experiencing right now. Are there any other similar neurologic recessive disorders similar to ALS, if I may ask? Just wanted to know, if my grandmother or grandfather was a carrier in a dominant version, is it possible that they just haven't developed the disease (they were in their mid 70's or close to 80's)?

Attached one of the report when shown to a prominent doctor in India and that was about 3 years ago.

Thank you for the answer.
 

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lgelb

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I redacted your dad's name.

On first impression, wondering if the recommended electrophoresis to rule out hemoglobinopathies was done? Some blood disorders can be inherited. Also, I do not see any testing for anti-GM1 antibodies.

There is no actual EMG report, but the conclusion indicates that demyelination was seen, a motor neuropathy but not ALS. It looks like they were thinking MMN. The lack of response to cyclophosphamide could suggest a pure lower motor neuron syndrome, but it's hard to say without the EMG (is there a more recent one?).

HIG, less toxic than cyclophosphamide, might still be worth trying if he is progressing and an exam/labs suggest that an immune-mediated neuropathy is still more likely than ALS. The ptosis they noted certainly is more suggestive of that than ALS. On the other hand, the bulbar symptoms you describe swing more back to ALS.

You said he had been diagnosed with MND by other docs; do you have the tests and reports that signify that? On the basis of what I see here, an immune-mediated neuropathy does seem more likely, but that was 3y ago and obviously things have changed.

Best,
Laurie
 
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sparrowking

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Thanks a lot for the reply.

I'm not in my home town right now, so don't have access to the reports. But, this is the report from the doctor who diagnosed my father as MND. 2 months back there was an ENMG test done, I'll share the report once I get it.

Thanks a lot.
 

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affected

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I don't see MND as a diagnostic feature in that report??
 
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