SELENON-related myopathy (SELENON-RM)

Overview

SELENON-related myopathy (SELENON-RM), caused by changes in the SELENON gene (formerly known as SEPN1), is one of the congenital myopathies — genetic muscle conditions present from birth or early infancy. Its hallmark features are weakness in the head, neck and torso muscles, breathing difficulties, and stiffness affecting the spine.

Symptoms

Signs are usually present at birth or within the first few months, though the diagnosis itself may not be reached until later in childhood. Early signs include low muscle tone, poor head control, and delays reaching milestones like sitting, crawling and walking, alongside difficulty gaining weight and growing.

Weakness is most pronounced in the head, neck and torso and worsens gradually; it also affects the upper arms and legs, making standing, using stairs and lifting objects harder. Both how severe it becomes and how quickly it progresses vary considerably between individuals. Most children go on to walk and continue to do so throughout life, though some need walking aids or a wheelchair as time goes on.

Weakness in the breathing muscles causes problems early on and needs regular monitoring — even relatively mild muscle weakness elsewhere can come with surprisingly significant breathing difficulty. Some people experience frequent chest infections, aspiration pneumonia (infection caused by food or fluid entering the airway), and nocturnal hypoventilation (shallow breathing overnight), which can cause morning headaches, daytime sleepiness, poor appetite and unintended weight loss. Non-invasive ventilation (NIV) at night is usually needed by the teenage years.

Joint contractures — tightening and shortening of muscles that restrict joint movement — commonly develop, especially at the ankles and elbows. Scoliosis (curvature of the spine) is also common, typically emerging in childhood and sometimes progressing quickly, so it needs specialist monitoring with regular X-rays; spinal braces can help support posture and slow its progression, and surgery is sometimes required. Many people also develop rigidity of the spine that makes bending forward difficult.

Chewing and swallowing can be affected by weakness in those muscles too, making eating slower and increasing the risk of choking or food/fluid entering the airway; combined with the difficulty gaining weight described above, many children and some adults are underweight and need dietitian input around nutrition, weight management and supplements.

Inheritance

The SELENON gene provides instructions for making a protein called selenoprotein N, which helps regulate calcium levels inside a structure in cells called the endoplasmic reticulum. Changes in the gene disrupt production or function of this protein, upsetting calcium regulation in a way that leads to the muscle weakness and other features described above.

SELENON-RM is typically autosomal recessive — a person needs two changed copies of the gene, one from each parent, to be affected. Parents who carry a single changed copy are unaffected carriers.

Getting a diagnosis

A GP can refer to a neurologist specialising in muscle and nervous system conditions. Diagnosis combines a physical examination with a genetic blood test checking for changes in the SELENON gene; a muscle biopsy, examining a small muscle sample under the microscope for the changes associated with SELENON-RM, is sometimes carried out as well. Related conditions that can show a similar picture include congenital muscular dystrophy with a rigid spine, multiminicore disease, desmin-related myopathy with Mallory body-like inclusions, and congenital fibre-type disproportion.

Management and outlook

Care works best through a multidisciplinary healthcare team, usually led by a neurologist at a specialist neuromuscular clinic. Staying active is encouraged — physiotherapists can design an exercise plan that keeps muscles engaged and helps prevent or slow the progression of joint stiffness, while moderate aerobic activity such as swimming, walking or cycling supports cardiovascular health and helps maintain a steady weight.

Breathing and lung capacity are checked regularly with spirometry, and overnight sleep studies assess breathing during sleep and check for nocturnal hypoventilation (a build-up of low oxygen and high carbon dioxide that causes morning headaches and daytime fatigue), which is treated with nighttime NIV. An annual flu vaccine, plus the pneumococcal vaccine for anyone using NIV, is recommended.

Orthopaedic input helps manage contractures and scoliosis through splints, braces, other orthotic devices, or spinal surgery where needed. A dietitian supports nutrition and weight management, including supplements where appropriate, and a speech and language therapist can assess swallowing difficulties and suggest a modified diet or other support if needed.