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Nemaline myopathy 8(NEM8)

MedGen UID:
Concept ID:
Disease or Syndrome
Synonyms: NEM8; Nemaline myopathy 8, autosomal recessive
Gene (location): KLHL40 (3p22.1)
Monarch Initiative: MONDO:0014138
OMIM®: 615348


Nemaline myopathy-8 is a severe autosomal recessive muscle disorder characterized by fetal akinesia or hypokinesia, followed by contractures, fractures, respiratory failure, and swallowing difficulties apparent at birth. Most patients die in infancy. Skeletal muscle biopsy shows numerous small nemaline bodies, often with no normal myofibrils (summary by Ravenscroft et al., 2013). For a discussion of genetic heterogeneity of nemaline myopathy, see NEM3 (161800). [from OMIM]

Additional description

From MedlinePlus Genetics
Nemaline myopathy is divided into six types. In order of decreasing severity, the types are: severe congenital, Amish, intermediate congenital, typical congenital, childhood-onset, and adult-onset. The types are distinguished by the age when symptoms first appear and the severity of symptoms; however, there is overlap among the various types. The severe congenital type is the most life-threatening. Most individuals with this type do not survive past early childhood due to respiratory failure. The Amish type solely affects the Old Order Amish population of Pennsylvania and is typically fatal in early childhood. The most common type of nemaline myopathy is the typical congenital type, which is characterized by muscle weakness and feeding problems beginning in infancy. Most of these individuals do not have severe breathing problems and can walk unassisted. People with the childhood-onset type usually develop muscle weakness in adolescence. The adult-onset type is the mildest of all the various types. People with this type usually develop muscle weakness between ages 20 and 50.

Nemaline myopathy is a disorder that primarily affects skeletal muscles, which are muscles that the body uses for movement. People with nemaline myopathy have muscle weakness (myopathy) throughout the body, but it is typically most severe in the muscles of the face; neck; trunk; and other muscles close to the center of the body (proximal muscles), such as those of the upper arms and legs. This weakness can worsen over time. Affected individuals may have feeding and swallowing difficulties, foot deformities, abnormal curvature of the spine (scoliosis), and joint deformities (contractures). Most people with nemaline myopathy are able to walk, although some affected children may begin walking later than usual. As the condition progresses, some people may require wheelchair assistance. In severe cases, the muscles used for breathing are affected and life-threatening breathing difficulties can occur.  https://medlineplus.gov/genetics/condition/nemaline-myopathy

Clinical features

From HPO
MedGen UID:
Concept ID:
Disease or Syndrome
Difficulty in swallowing.
Gastrostomy tube feeding in infancy
MedGen UID:
Concept ID:
Feeding problem necessitating gastrostomy tube feeding.
Muscle weakness
MedGen UID:
Concept ID:
Reduced strength of muscles.
Flexion contracture
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Concept ID:
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Facial palsy
MedGen UID:
Concept ID:
Disease or Syndrome
Facial nerve palsy is a dysfunction of cranial nerve VII (the facial nerve) that results in inability to control facial muscles on the affected side with weakness of the muscles of facial expression and eye closure. This can either be present in unilateral or bilateral form.
Myofibrillar myopathy
MedGen UID:
Concept ID:
Other signs and symptoms of myofibrillar myopathy can include a weakened heart muscle (cardiomyopathy), muscle pain (myalgia), loss of sensation and weakness in the limbs (peripheral neuropathy), and respiratory failure. Individuals with this condition may have skeletal problems including joint stiffness (contractures) and abnormal side-to-side curvature of the spine (scoliosis). Rarely, people with this condition develop clouding of the lens of the eyes (cataracts).\n\nThe signs and symptoms of myofibrillar myopathy vary widely among affected individuals, typically depending on the condition's genetic cause. Most people with this disorder begin to develop muscle weakness (myopathy) in mid-adulthood. However, features of this condition can appear anytime between infancy and late adulthood. Muscle weakness most often begins in the hands and feet (distal muscles), but some people first experience weakness in the muscles near the center of the body (proximal muscles). Other affected individuals develop muscle weakness throughout their body. Facial muscle weakness can cause swallowing and speech difficulties. Muscle weakness worsens over time.\n\nMyofibrillar myopathy is part of a group of disorders called muscular dystrophies that affect muscle function and cause weakness. Myofibrillar myopathy primarily affects skeletal muscles, which are muscles that the body uses for movement. In some cases, the heart (cardiac) muscle is also affected.
Nemaline bodies
MedGen UID:
Concept ID:
Nemaline rods are abnormal bodies that can occur in skeletal muscle fibers. The rods can be observed on histological analysis of muscle biopsy tissue or upon electron microscopy, where they appear either as extensions of sarcomeric Z-lines, in random array without obvious attachment to Z-lines (often in areas devoid of sarcomeres) or in large clusters localized at the sarcolemma or intermyofibrillar spaces.
Respiratory failure
MedGen UID:
Concept ID:
Disease or Syndrome
A severe form of respiratory insufficiency characterized by inadequate gas exchange such that the levels of oxygen or carbon dioxide cannot be maintained within normal limits.
MedGen UID:
Concept ID:
Pathologic Function
The presence of excess amniotic fluid in the uterus during pregnancy.
Decreased fetal movement
MedGen UID:
Concept ID:
An abnormal reduction in quantity or strength of fetal movements.
Fetal akinesia deformation sequence 1
MedGen UID:
Concept ID:
Disease or Syndrome
Decreased fetal activity associated with multiple joint contractures, facial anomalies and pulmonary hypoplasia. Ultrasound examination may reveal polyhydramnios, ankylosis, scalp edema, and decreased chest movements (reflecting pulmonary hypoplasia).
MedGen UID:
Concept ID:
Sign or Symptom
Ophthalmoplegia is a paralysis or weakness of one or more of the muscles that control eye movement.

Professional guidelines


Scheibe F, Ostendorf L, Prüss H, Radbruch H, Aschman T, Hoffmann S, Blau IW, Meisel C, Alexander T, Meisel A
Eur J Neurol 2022 Jun;29(6):1847-1854. Epub 2022 Feb 10 doi: 10.1111/ene.15266. PMID: 35098616
Kotchetkov R, Susman D, Bhutani D, Broch K, Dispenzieri A, Buadi FK
Int J Cancer 2021 Jun 1;148(11):2807-2814. Epub 2021 Feb 12 doi: 10.1002/ijc.33483. PMID: 33529362
Naddaf E, Milone M, Kansagra A, Buadi F, Kourelis T
Neurology 2019 Jul 16;93(3):e298-e305. Epub 2019 Jun 5 doi: 10.1212/WNL.0000000000007777. PMID: 31167932

Recent clinical studies


Yeung KS, Yu FNY, Fung CW, Wong S, Lee HHC, Fung STH, Fung GPG, Leung KY, Chung WH, Lee YT, Ng VKS, Yu MHC, Fung JLF, Tsang MHY, Chan KYK, Chan SHS, Kan ASY, Chung BHY
Mol Genet Genomic Med 2020 Jul;8(7):e1229. Epub 2020 Apr 30 doi: 10.1002/mgg3.1229. PMID: 32352246Free PMC Article


Dofash LNH, Monahan GV, Servián-Morilla E, Rivas E, Faiz F, Sullivan P, Oates E, Clayton J, Taylor RL, Davis MR, Beilharz T, Laing NG, Cabrera-Serrano M, Ravenscroft G
Hum Mol Genet 2023 Mar 20;32(7):1127-1136. doi: 10.1093/hmg/ddac272. PMID: 36322148

Clinical prediction guides

Dofash LNH, Monahan GV, Servián-Morilla E, Rivas E, Faiz F, Sullivan P, Oates E, Clayton J, Taylor RL, Davis MR, Beilharz T, Laing NG, Cabrera-Serrano M, Ravenscroft G
Hum Mol Genet 2023 Mar 20;32(7):1127-1136. doi: 10.1093/hmg/ddac272. PMID: 36322148

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