Table 2. Features of Titin-Related Skeletal Musical Disorders.

Dominant Inheritance		Recessive Inheritance
Disease
HMERF	TMD	LGMD2J	Adult-onset distal myopathy	Proximal adult-onset rimmed vacuolar myopathy	Congenital or early onset titinopathies
Genetics
Heterozygous exon 344 mutations	Heterozygous exon 364 mutations	Homozygosity (mainly exon 364 mutations)a Compound heterozygosity (mainly exon 364 + truncating mutations)a		Compound heterozygosity (exon 364 + missense mutations)	Compound heterozygosity (mainly truncating variants)
Key Point(s)
Respiratory muscle weakness; “necklace” cytoplasmic bodies and myofibrillar changes in muscle biopsies	Degeneration of the muscles of the anterior lower legs starting in the anterior tibial muscle	Slowly progressive fatty degeneration (preserved muscles can be found in young patients)	Severe degeneration of tibialis anterior and soleus (unusual in TMD)	Prominent quadriceps and soleus involvement (sparing of tibial muscle); peculiar rimmed vacuoles in their muscle biopsies	Cardiac involvement often seen; sparing of extraocular muscles; early degeneration of semitendinosus, soleus, and peroneal; late involvement of the rectus femoris and vasti

^a The clinical phenotype depends on the specific exon 364 mutation.