Characteristics of SEPN1-RM
Poor head control
Reduced vital capacity and nocturnal hyperventilation.
Respiratory failure while still ambulatory
Clinical symptoms of SEPN1-RM may resemble other congenital muscular dystrophies, especially those involving spine rigidity. The key clinical features of SEPN1-RM (weak axial muscles, respiratory insufficiency while still ambulant) will differentiate it from other forms of CMD. Genetic testing may provide a definitive diagnosis.
SEPN1-RM is inherited in an autosomal recessive fashion, meaning there must be two pathogenic mutations present to cause symptoms. These mutations may be inherited from each parent, or may be denovo (spontaneous). It is not uncommon for affected individuals to only have had one of the two mutations identified through genetic testing. Parental testing may be pursued to confirm findings. One identified mutation along with identifiable physical characteristics can lead to a confirmed diagnosis.
Physiology of SEPN1-RM
Selenoprotein N1 is part of the selenoprotein family. Selenoproteins are primarily involved in chemical reactions called oxidation-reduction reactions, which are essential for protecting cells from damage caused
by unstable oxygen-containing molecules. Selenoprotein N, 1 is likely involved in protecting cells against oxidative stress. Oxidative stress occurs when unstable molecules called free radicals accumulate to
levels that damage or kill cells.
The exact function of selenoprotein N, 1 is unknown. This protein is highly active in many tissues before birth and may be involved in the formation of muscle tissue (myogenesis). Selenoprotein N, 1 may also
be important for normal muscle function after birth, although it is active at much lower levels in adult tissues. This protein contains a region that likely allows it to bind to calcium. This region is of interest because calcium plays an important role in triggering muscle contractions, allowing the body to move.
The first symptoms of those born with SEPN1 are likely weak muscle tone and/or floppiness with delayed motor skills such as crawling or walking. Muscle weakness is most likely first limited to the trunk and neck.
Affected individuals may have difficulty holding up their heads. Walking is achieved, but can become difficult due to spine rigidity and rapidly developing scoliosis. Respiratory insufficiency can develop during the first decade of life, even while the affected individual is still ambulant, leading to nocturnal hyperventilation that requires night time non-invasive ventilation. Affected individuals are likely of short stature and have difficulty gaining weight.