Molecular Genetics and Genetic Testing in Myotonic Dystrophy Type 1

Table 2

Reporting guidelines for DM1 genetic testing according to Kamsteeg et al. [106] complemented with the influence of gender of the transmitting parent.

Genetic test result	Recommended reporting
No expansion-homozygous or heterozygous for allele in the size range of 5–35 repeats (normal alleles)	DM1 diagnosis is excluded; when it concerns a fetus, it is not affected.
	(i) DM1 diagnosis is excluded; when it concerns a fetus, it is not affected.
A heterozygous expansion in the size range of 36–50 repeats (premutation alleles)	(ii) Premutations may or may not expand in next generations. Transmission by female mostly results in stable inheritance or small changes in repeat copy number, while when transmitted by men, they are more prone to expand, even reaching the disease-associated mutation in a single generation, thus raising the risk of having affected child.
	(iii) Relatives (including offspring) of the counselee may be at risk of developing DM1 and should be offered counseling. An offer of repeat-length analysis to those relatives is warranted.
	(i) When symptoms are evident, the diagnosis of DM1 is confirmed.
	(ii) When symptoms of DM1 are not evident (asymptomatic family member or fetus), the individual is at risk of developing DM1, although individuals with a repeat expansion of this size may also remain symptomless.
A heterozygous expansion in the size range of 51–150 repeats	(iii) Counselees in the reproductive age is warranted. Smaller repeat expansion of this size range can be stably transmitted by female, while larger repeat expansion of this size range raising the risk of having a child with even congenital form of DM1. When transmitted by male repeat expansion of this size range almost invariably results in a large increase into the disease-associated mutation, raising the risk of having affected offspring.
	(iv) Relatives (including offspring) of the counselee may be at risk of developing DM1. Due to anticipation in DM1, offspring may be more severely affected. Relatives should therefore be offered counseling. An offer of repeat-length analysis to those relatives is warranted.
	(i) When symptoms are evident, the diagnosis of DM1 is confirmed.
	(ii) When symptoms of DM1 are not evident (asymptomatic family member), the individual is at risk of developing DM1, although individuals with a repeat expansion of this size range may rarely remain symptomless.
A heterozygous expansion with a size over 150 repeats	(iii) When it concerns a fetus, it is very likely to be affected and has a high risk to be more severely affected than the affected parent.
	(iv) Counselees in the reproductive age is warranted. Women are, especially, at risk of having children with the congenital form of DM1.
	(v) Relatives (including offspring) of the counselee may be at risk of developing DM1. Due to anticipation in DM1, the offspring may be more severely affected. Therefore, relatives should be offered counseling. An offer of repeat-length analysis to those relatives is warranted.