Multiminicore disease (MmD)

Overview

Multiminicore disease (MmD) — sometimes called minicore or multiminicore myopathy — is a congenital myopathy, present from birth or infancy, that causes muscle weakness. It's named for the 'minicores' seen on a muscle biopsy: small, distinctive areas within individual muscle fibres. Several different genes can cause MmD, and the specific gene involved shapes both the symptoms and how severe they are.

Symptoms

The classic, SELENON-related form usually starts at birth or in the first months of life, with low muscle tone and weakness concentrated in the trunk and the limb muscles closest to it, alongside delayed motor milestones. Most people with this form do go on to walk independently and keep that ability into adulthood, though weakness is generally more pronounced in the neck and trunk than the limbs. A rigid spine, scoliosis and breathing difficulties are common, and some need a feeding tube.

The RYR1-related form is much more variable: weakness is usually worst in the muscles closest to the trunk, and eye-movement weakness (sometimes with drooping eyelids) is common. Some people have loose joints, scoliosis, and mild feeding or breathing difficulties that still need monitoring; severe cases can rarely involve contractures present at birth from reduced movement in the womb, alongside a longer head shape, low-set ears and a short neck, plus moderate-to-severe breathing muscle involvement.

MYH7-related MmD tends to cause slowly progressive weakness in the feet and toes in particular, often with scoliosis, breathing difficulties and a risk of heart involvement — though how severely someone is affected varies a great deal, and some have very little weakness at all. TTN-related MmD causes slowly progressive weakness from birth, commonly with scoliosis, spinal rigidity, contractures, and weakness affecting both breathing and the heart.

Inheritance and cause

Most MmD is linked to the SELENON or RYR1 genes, with rarer cases involving MYH7 or TTN. SELENON changes disrupt both muscle fibre structure and the muscle's defences against oxidative stress; RYR1 changes disrupt the muscle's ability to contract and relax properly, and — importantly — also carry a risk of malignant hyperthermia, a potentially life-threatening anaesthetic reaction. Most forms of MmD are autosomal recessive (a changed copy needed from both parents); the MYH7-related form is the exception, being autosomal dominant. Occasionally the genetic change arises with no family history at all.

Getting a diagnosis

A GP typically refers a child to a paediatrician first, who involves a neurologist if needed. Diagnosis usually combines a physical assessment with muscle MRI and a muscle biopsy alongside genetic testing; the biopsy characteristically shows more type 1 fibres than usual, along with the minicore structures the condition is named for. Genetic blood testing confirms the specific gene involved, and — once identified in one family member — can be used to test relatives and identify unaffected carriers, sometimes avoiding the need for a biopsy altogether in those cases.

Management and outlook

A multidisciplinary team, usually led by a neurologist, coordinates care. Physiotherapy and gentle exercise (swimming, walking, cycling are commonly suggested) help maintain strength and mobility, support breathing capacity, and slow the progression of contractures and scoliosis, while also supporting general cardiovascular health and a steady weight.

Orthopaedic input — splints, braces, orthotic devices or surgery — helps manage contractures and scoliosis depending on individual needs. Respiratory weakness is common, especially in the SELENON-related form, so lung function and breathing capacity should be checked regularly, with an annual flu vaccine to help guard against chest infections; overnight sleep studies can pick up nocturnal hypoventilation, which non-invasive ventilation treats effectively.

Some forms of MmD — particularly those linked to RYR1, MYH7 or TTN — carry a risk of cardiomyopathy, so regular heart monitoring (ECG, echocardiogram, Holter monitoring) is worthwhile. Before any surgery, anaesthetists and the wider surgical team need to know about the diagnosis and any breathing or heart complications; RYR1-related MmD in particular carries a serious risk of malignant hyperthermia under anaesthesia (rapid temperature rise, muscle rigidity, a fast heart rate, muscle breakdown and dark urine), which needs immediate treatment with dantrolene and active cooling — certain anaesthetic drugs should be avoided altogether in anyone with this form.