1. Demographics
We collected answers from 30 POs (response rate of 26%) based in 18 European countries. Of these 18 countries, 17 were EU countries, and 10 were members of the ERN EURO-NMD. (Fig 1)
Figure 1
Legend – Number of countries (18) and the number of answers per country: Belgium (1), Bulgaria (1), Czech Republic (1), Denmark (1), Germany (1), Greece (1), Italy (1), Luxembourg (1), The Netherlands (1), Poland (1), Portugal (1), Serbia (1), Switzerland (1), United-Kingdom (1), France (2), North Macedonia (2), Romania (2), Spain (10).
Two main categories of patients’ associations were included in the survey: “all-neuromuscular diseases organisations” that represent all NMDs and those dedicated to a disease or thematic group of NMD. The “all-neuromuscular diseases organisations” provided 43.3% (13/30) of the answers, and the disease-specific organisations 56.7%. Figure 2, represents the disease coverage across organisations. It is noticeable that besides the “all-neuromuscular diseases organisations”, the majority were organisations dedicated to Duchenne/Becker muscular dystrophy (DMD/BMD) or spinal muscular atrophy (SMA).
Figure 2
Legend: Number of responses per type of patient organisation. Umbrella Org. – “all-neuromuscular diseases organisations”; DMD/BMD - Duchenne and Becker muscular dystrophy organisations; SMA – spinal muscular atrophy organisations; LGMD – limb girdle muscular dystrophies organisation; CMD – congenital muscular dystrophies organisations; GNE – GNE myopathy organisation (GNEM).
2. The current reported situation regarding screening in the different countries
2.1 Pre-implantation diagnostic (PGD)
Regarding the question “Is PGD in place in your country?” 15/30 associations from 10/18 countries (Spain, Romania, Portugal, The Netherlands, Greece, Germany, France, Bulgaria, Belgium, UK) responded affirmatively. When we analysed the answers per country, we noticed an inconsistency. Half of the associations from Spain (5/10) and Romani (1/2) mentioned that PGD was available, while the other 50% stated that PDG was not available.
When PGD was available, we specifically asked if and which NMDs were included. For 14/15, the answer was positive; only for Portugal, it was stated that PGD did not include NMD. According to the responses collected and depending on the country, PGD is available for Duchenne and Becker muscular dystrophy (DMD), spinal muscular atrophy (SMA), Charcot-Marie-Tooth neuropathy (CMT), amyotrophic lateral sclerosis (ALS), myasthenia gravis (MG), myotonic dystrophy (MD) and facioscapulohumeral muscular dystrophy (FSHD). There is an obvious caveat in the answers we have received as some non-genetic diseases were mentioned. (Table 2)
Table 2: Availability of screening methods for neuromuscular diseases
Country
|
Type of organisation
|
Is PGD available?
|
Includes NMD?
|
Is PNS in place?
|
Includes NMD?
|
Is NBS in place?
|
Includes NMD?
|
BE
|
Disease specific
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
BG
|
All NMD
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
CZ
|
Disease specific
|
No
|
No
|
Yes
|
No
|
Yes
|
No
|
DK
|
All NMD
|
No
|
No
|
Yes
|
No
|
Yes
|
No
|
FR
|
Disease specific
|
Yes
|
Yes
|
Yes
|
Yes
|
No
|
No
|
FR
|
All NMD
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
No
|
DE
|
All NMD
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
No
|
GR
|
All NMD
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
IT
|
Disease specific
|
No
|
No
|
Yes
|
Yes
|
Yes
|
Yes
|
LU
|
All NMD
|
No
|
No
|
Yes
|
No
|
Yes
|
No
|
NL
|
All NMD
|
Yes
|
Yes
|
No
|
No
|
Yes
|
No
|
MK
|
Disease specific
|
No
|
No
|
Yes
|
Yes
|
No
|
No
|
MK
|
All NMD
|
No
|
No
|
Yes
|
Yes
|
No
|
No
|
PL
|
All NMD
|
No
|
No
|
Yes
|
Yes
|
Yes
|
No
|
PT
|
All NMD
|
Yes
|
No
|
No
|
No
|
Yes
|
No
|
RO
|
Disease specific
|
No
|
No
|
Yes
|
No
|
Yes
|
No
|
RO
|
Disease specific
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
RS
|
Disease specific
|
No
|
No
|
Yes
|
No
|
No
|
No
|
ES
|
All NMD
|
No
|
No
|
No
|
No
|
No
|
No
|
ES
|
Disease specific
|
No
|
No
|
Yes
|
No
|
Yes
|
No
|
ES
|
Disease specific
|
No
|
No
|
Yes
|
No
|
Yes
|
No
|
ES
|
All NMD
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
ES
|
Disease specific
|
Yes
|
Yes
|
No
|
No
|
Yes
|
Yes
|
ES
|
Disease specific
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
ES
|
All NMD
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
ES
|
Disease specific
|
No
|
No
|
Yes
|
No
|
No
|
No
|
ES
|
Disease specific
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
ES
|
Disease specific
|
No
|
No
|
No
|
No
|
Yes
|
No
|
CH
|
Disease specific
|
No
|
No
|
No
|
No
|
Yes
|
No
|
UK
|
Disease specific
|
Yes
|
Yes
|
Yes
|
No
|
Yes
|
No
|
Legend: Representation of the answers across countries and type of PO regarding the different screening techniques
2.2 Prenatal screening (PNS)
Regarding the availability of prenatal screening (PNS) in different countries, we had 25 positive answers and 5 negative ones corresponding to 3 countries: Spain, Portugal and Switzerland.
Once more, we had collected some conflicting answers with 7 Spanish associations saying that PNS was available and three saying that it was not. Some of the diseases included in the responses were diseases for which PNS is not available. PNS would cover, depending on the countries, Duchenne and Becker muscular dystrophy (DMD), spinal muscular atrophy (SMA), Charcot-Marie-Tooth neuropathy (CMT), motor neuron disease (ALS), myasthenia gravis (MG), myotonic dystrophy (DM), Limb-Girdle Muscular dystrophy (LGMD) and Amyloidosis (AM). (Table 2)
2.3 Newborn screening (NBS)
To the question “is newborn screening available in your country”, 24 associations said yes and 6, from 4 different countries, said no (France -1, North Macedonia - 2, Serbia - 1, Spain - 2). Fourteen associations mentioned that NBS did not include NMD and ten said that NMD was part of the newborn screening program in their country (Belgium (1), Bulgaria (1), Greece (1), Italy (1), Romania (1), Spain (5)). In Bulgaria, all genetically transmitted NMD are reported as being part of the NBS program. NMD that were referred to as being part of the NBS programs were DMD, SMA, POMPE (Italy), Myotonic dystrophy (Spain). NBS was recently approved in the Netherlands for SMA and at it had been refused for Pompe disease. In Italy, in December 2018, an amendment was adopted which extended the newborn screening to NMD although the diseases to be included were still undefined. In June 2019 and for two years, a pilot project for NBS for SMA was launched in the regions of Lazio and Tuscany. In addition, Germany has in place a pilot project for NBS for SMA.
Once more, we noticed a lack of information regarding the real situation of NBS in each country. All European countries, except Albania, have NBS programs, the main differences being the number of diseases included, between 1 and 30. Therefore, NBS is available in almost all European countries, and the disease coverage was extended after the introduction of tandem mass spectrometry.
3. Views of patients’ organisations regarding screening for NMD
As screening for genetic conditions can conjure very personal believes, either religious or ethical and raise economic issues we wanted to know if the patients’ organisations (POs) involved in this survey were in favour of screening for the conditions that are relevant to their organisation. Twenty-eight organisations were in favour of testing for the conditions they advocate for. The reasons given for the two negative answers were lack of reimbursement, lack of treatment, religious beliefs and that a positive test would make it difficult or very expensive to get a mortgage or an insurance. (table 3)
Table 3: Reasons why the POs were not in favour of screening
Country
|
Absence of disease-modifying treatment
|
Personal, cultural or religious beliefs
|
Lack of reimbursement
|
Pricy/ impossible mortgage/insurance
|
Poland
|
1
|
3
|
1
|
1
|
Spain
|
2
|
1
|
1
|
5
|
Legend: Answers ranged from 1 to 5. 1 being the most important reason, 5 the least.
From the POs in favour of screening, we further wanted to know when and how they preconized it should be implemented, if it should be systematic and if it was preferable to implement an opt-in or opt-out system. A summary of the answers can be seen in table 4.
Table 4: How and when to screen
Modality of screening
|
Number of answers
|
When should screening take place?
|
Number of answers
|
Systematic with the option to opt-out
|
21
|
At birth
|
9
|
Early pregnancy
|
6
|
Preconception
|
4
|
Depends on the disease and the situation
|
3
|
Systematic
|
4
|
At birth
|
2
|
Early pregnancy
|
1
|
Preconception
|
1
|
Not systematic with the possibility to opt-in
|
3
|
At birth
|
1
|
Depends on the disease and the situation
|
1
|
Preconception
|
1
|
Most PO (21) were in favour of systematic screening with the option to opt-out. The opt-out option was preferred regardless of the type of association, disease-specific or all-neuromuscular diseases. (table 5).
Table 5: How to screen: answers from POs by the pathologies they represented
|
DMD
|
SMA
|
NMD
|
OTHER
|
TOTAL
|
Systematic with the option to opt-out
|
5 (83%)
|
5 (100%)
|
7 (58%)
|
4 (80%)
|
21
|
Systematic
|
1 (17%)
|
0
|
3 (25%)
|
0
|
4
|
Not systematic with the possibility to opt-in
|
0
|
0
|
2 (17%)
|
1 (20%)
|
3
|
Legend: “DMD” stands for DMD/BMD patients’ organisations (n=6), “SMA” for SMA POs (n=5), “NMD” for all neuromuscular diseases POs (n=12), “Other” for other neuromuscular diseases specific POs (n=5).
When we look at the answers for when should screening take place, we see divided opinions; however, “at birth” seem to reunite most of the responses (12).
When we look at the organisations devoted to SMA, it is unanimous that the screening should occur at birth. However, early pregnancy and pre-conception screening were also strongly envisaged for other neuromuscular diseases organisations. (table 6).
Table 6: When to Screen answers from POs by the pathologies they represented
When
|
DMD
|
SMA
|
NMD
|
OTHER
|
TOTAL
|
Pre-conception
|
3 (50%)
|
0
|
2 (17%)
|
1 (20%)
|
6
|
Early pregnancy
|
2 (33%)
|
0
|
2 (17%)
|
3 (60%)
|
7
|
At birth
|
1 (17%)
|
5 (100%)
|
5 (42%)
|
1 (20%)
|
12
|
It depends
|
0
|
0
|
3 (25%)
|
0
|
3
|
Legend: “DMD” stands for DMD/BMD patients’ organisations (n=6), “SMA” for SMA POs (n=5), “NMD” for all neuromuscular diseases POs (n=12), “Other” for other neuromuscular diseases specific POs (n=5).
We also inquired about the reason(s) why screening should take place and asked the participants to select the relevant reasons and rank them (1 being the most important, 6 the least). Summary of the answers can be seen in table 7.
When we analysed all the answers (28) priority was given to early access to treatment, followed with equal importance by shorter time to set the diagnosis, preventive care and genetic counselling. The inclusion in clinical trials was the question that scored the lowest value in terms of importance. The answers of the “all-neuromuscular diseases organisations” were very similar to the aggregated responses. (Supplementary Table 1).
Table 7: Reasons why POs where in favour of screening
Rank
|
shorter time to diagnostic
|
early access to treatments
|
inclusion in clinical trials
|
preventive care
|
genetic counselling
|
1
|
13 (50%)
|
18 (69%)
|
8 (33%)
|
11 (44%)
|
13 (48%)
|
2
|
7 (27%)
|
5 (19%)
|
6 (25%)
|
9 (36%)
|
7 (26%)
|
3
|
3 (12%)
|
1 (4%)
|
4 (17%)
|
3 (12%)
|
4 (15%)
|
4
|
2 (8%)
|
2 (8%)
|
0
|
2 (8%)
|
2 (7%)
|
5
|
1 (4%)
|
0
|
5 (21%)
|
0
|
1 (4%)
|
6
|
0
|
0
|
1 (4%)
|
0
|
0
|
Legend: aggregated results for all patients’ organisations (n=28). 1= most important, 6 = least important.
However, when we analyse at the specific pathology level answers can be radically different.
On the one hand, for the SMA organisations, priority was given to early access to treatment. (Supplementary Table 2). On the other hand, for DMD associations, priority was given to preventive care and genetic counselling. (Supplementary Table 3).