Fetal akinesia deformation sequence: genes and variants

Genes linked to Fetal akinesia deformation sequence

• MUSK: Muscle, skeletal receptor tyrosine-protein kinase

  It organizes the postsynaptic neuromuscular junction by responding to agrin-LRP4 signaling and clustering acetylcholine receptors. Biallelic pathogenic variants cause congenital myasthenic syndrome, while autoantibodies against MuSK cause an important subtype of acquired myasthenia gravis.

  5 disease-causing and 234 uncertain variants in MUSK are linked to Fetal akinesia deformation sequence.

• SCN4A: Sodium channel protein type 4 subunit alpha

  Its rapid sodium current initiates and propagates skeletal-muscle action potentials. Gain- and loss-of-function variants cause disorders of muscle excitability including sodium-channel myotonia, paramyotonia congenita, periodic paralysis, and some congenital myopathies.

  1 disease-causing and 0 uncertain variants in SCN4A are linked to Fetal akinesia deformation sequence.

• SCN8A: Sodium channel protein type 8 subunit alpha

  The protein forms Nav1.6, a voltage-gated sodium channel that sets the threshold and propagation of neuronal action potentials. It is widely important for neuronal excitability, and SCN8A variants are associated with developmental and epileptic encephalopathies.

  1 disease-causing and 0 uncertain variants in SCN8A are linked to Fetal akinesia deformation sequence.

• RYR1: Ryanodine receptor 1

  It releases calcium from the skeletal-muscle sarcoplasmic reticulum when Cav1.1 senses membrane depolarization, directly coupling excitation to contraction. Pathogenic variants cause malignant-hyperthermia susceptibility and a broad spectrum of congenital RYR1-related myopathies.

  0 disease-causing and 0 uncertain variants in RYR1 are linked to Fetal akinesia deformation sequence.

Weakly linked (only a few uncertain records): RYR3.

Known disease-causing variants in Fetal akinesia deformation sequence

Same protein, different disease

• Congenital myasthenic syndrome 17 is also caused by MUSK variants; they fall mostly in different places as the Fetal akinesia deformation sequence variants (9 disease-causing).
• Hyperkalemic periodic paralysis is also caused by SCN4A variants; they fall mostly in different places as the Fetal akinesia deformation sequence variants (62 disease-causing).
• Paramyotonia congenita of Von Eulenburg is also caused by SCN4A variants; they fall mostly in different places as the Fetal akinesia deformation sequence variants (15 disease-causing).
• Potassium-aggravated myotonia is also caused by SCN4A variants; they fall mostly in different places as the Fetal akinesia deformation sequence variants (14 disease-causing).
• Hypokalemic periodic paralysis is also caused by SCN4A variants; they fall mostly in different places as the Fetal akinesia deformation sequence variants (11 disease-causing).
• Congenital myopathy 22A, classic is also caused by SCN4A variants; they fall mostly in different places as the Fetal akinesia deformation sequence variants (8 disease-causing).
• Early-infantile DEE is also caused by SCN8A variants; they fall mostly in different places as the Fetal akinesia deformation sequence variants (90 disease-causing).
• Cognitive impairment with or without cerebellar ataxia is also caused by SCN8A variants; they fall mostly in different places as the Fetal akinesia deformation sequence variants (22 disease-causing).
• Seizures, benign familial infantile, 3 is also caused by SCN8A variants; they fall mostly in different places as the Fetal akinesia deformation sequence variants (12 disease-causing).
• Complex neurodevelopmental disorder is also caused by SCN8A variants; they fall mostly in different places as the Fetal akinesia deformation sequence variants (8 disease-causing).
• Autosomal recessive inheritance is also caused by SCN8A variants; they fall mostly in different places as the Fetal akinesia deformation sequence variants (3 disease-causing).

Diseases related to Fetal akinesia deformation sequence

• Arthrogryposis multiplex congenita, also linked to RYR1, SCN4A and SCN8A
• Amyotrophic lateral sclerosis, also linked to SCN4A and SCN8A
• Cardiac arrhythmia, also linked to SCN4A and SCN8A
• Congenital myasthenic syndrome 17, also linked to MUSK and SCN4A
• Epilepsy, also linked to SCN4A and SCN8A
• Early-infantile DEE, also linked to SCN8A
• Seizures, benign familial infantile, 3, also linked to SCN8A
• Sotos syndrome, also linked to SCN4A
• Hyperkalemic periodic paralysis, also linked to SCN4A
• Complex neurodevelopmental disorder, also linked to SCN8A
• Hypokalemic periodic paralysis, also linked to SCN4A
• Cognitive impairment with or without cerebellar ataxia, also linked to SCN8A

Frequently asked questions

Which genes are linked to Fetal akinesia deformation sequence?

In CATVariant, Fetal akinesia deformation sequence is linked to 4 analyzed proteins: MUSK (Muscle, skeletal receptor tyrosine-protein kinase), SCN4A (Sodium channel protein type 4 subunit alpha), SCN8A (Sodium channel protein type 8 subunit alpha) and RYR1 (Ryanodine receptor 1).

How many genetic variants are linked to Fetal akinesia deformation sequence?

271 variants: 7 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 235 are of uncertain significance or have conflicting reports.

Which uncertain variants in Fetal akinesia deformation sequence look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

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