Severe infantile hyperkalaemic periodic paralysis and paramyotonia congenita: broadening the clinical spectrum associated with the T704M mutation in SCN4A

Brancati, Francesco; Valente, Enza Maria; Davies, Nicholas; Sárközy, Anna; Sweeney, MG; LoMonaco, M; Pizzuti, Antonio; Hanna, Michael G.; Dallapiccola, Bruno

doi:10.1136/jnnp.74.9.1339

Cited by 36 publications

(36 citation statements)

References 21 publications

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“…Serum potassium levels were normal but were not measured during attacks of myotonia or weakness. Muscle biopsy was also non-specific and did not reveal vacuolar changes or abnormalities in proportions of fiber-type as previously described [Heene et al, 1986;Brancati et al, 2003;Miller et al, 2004]. Myotonia and hip dislocation led to the suspicion of Schwartz-Jampel syndrome, which was ruled out by normal perlecan sequencing results on fibroblasts.…”

Section: Discussionmentioning

confidence: 60%

“…Another report of PC-HYPP overlap syndrome with severe early onset was described in an Italian kindred with nine affected individuals [Brancati et al, 2003]. The onset of weakness episodes began in the first year of life and persisted into adult life.…”

Section: Discussionmentioning

confidence: 97%

“…Therapy is based on local anaesthetics and class 1b antiarrhythmic agents such as lidocaine, mexiletine, and other lidocaine derivates [Jackson et al, 1994;Meola and Sansone, 2000]. Only one family with a PC-HYPP overlap syndrome has been described with a severe infantile presentation [Brancati et al, 2003]. Here, we report on a patient with severe fatal neonatal non-dystrophic myotonia secondary to a mutation in an intracytoplasmic loop of the SCN4A gene product.…”

Section: Introductionmentioning

confidence: 93%

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Severe neonatal non‐dystrophic myotonia secondary to a novel mutation of the voltage‐gated sodium channel (SCN4A) gene

Gay

Dupuis

Faivre

et al. 2008

American J of Med Genetics Pt A

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We report on a patient with a severe, rare neonatal form of non-dystrophic myotonia. The patient presented with facial dysmorphism, muscle hypertrophy, severe constipation, psychomotor delay, and frequent cold-induced episodes of myotonia and muscle weakness leading to severe hypoxia and loss of consciousness. Muscle biopsy was non-specific and electromyography revealed intense generalized myotonia. The myotonic episodes improved after introducing oral mexiletine and maintaining room temperature at 28 degrees C. The patient died at 20 months of age following a bronchopulmonary infection. A previously undescribed de novo heterozygous c.3891C > A change, which predicts p.N1297K in the SCN4A gene. Mutations within the voltage-gated sodium channel alpha-subunit gene (SCN4A) have been described in association with several phenotypes including paramyotonia congenita, hyperkalemic or hypokalemic periodic paralysis, and potassium-aggravated myotonias. The cold-sensitive episodes of stiffness followed by weakness suggested the diagnosis of channelopathy in our patient. However, her neonatal onset, the triggering of severe episodes by exposure to modest decreases in temperature, involvement of respiratory muscles with prolonged apnea, early-onset muscle hypertrophy, psychomotor retardation, and fatal outcome are evocative of a distinct clinical subtype. Our observation expands the phenotypic spectrum of sodium channelopathies.

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 93%

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Severe neonatal non‐dystrophic myotonia secondary to a novel mutation of the voltage‐gated sodium channel (SCN4A) gene

Gay

Dupuis

Faivre

et al. 2008

American J of Med Genetics Pt A

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“…20 In typical hyperkalemic PP mutations such as T704M and M1592V, paramyotonic signs have been reported in single families. [31][32][33] The reason for the clinical variability is unknown.…”

Section: Hyperkalemic Pp and Pc: Phenotypic Overlapmentioning

confidence: 99%

Genotype-Phenotype Correlation and Therapeutic Rationale in Hyperkalemic Periodic Paralysis

Jurkat‐Rott¹,

Lehmann‐Horn²

2007

Neurotherapeutics

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Summary:Familial hyperkalemic periodic paralysis (PP) is a dominantly inherited muscle disease characterized by attacks of flaccid weakness and intermittent myotonia. Some patients experience muscle stiffness that is aggravated by cold and exercise, bordering on the diagnosis of paramyotonia congenita. Hyperkalemic PP and paramyotonia congenita are allelic diseases caused by gain-of-function mutations of the skeletal muscle sodium channel, Nav1.4, which is essential for the generation of skeletal muscle action potentials. In this review, the functional and clinical consequences of the mutations and therapeutic strategies are reported and the differential diagnoses discussed. Also, the question is addressed of whether hyperkalemic PP is truly a different entity than normokalemic PP. Additionally, the differential diagnosis of Andersen-Tawil syndrome in which hyperkalemic PP attacks may occur will be briefly introduced. Last, because hyperkalemic PP has been described to be associated with an R83H mutation of a MiRP2 potassium channel subunit, evidence refuting disease-causality in this case will be discussed.

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“…Skeletal muscle channelopathies usually present as childhood onset dominant disorders, in the form of periodic paralysis, paramyotonia congenita, or sodium channel myotonia. [1][2][3][4] It has been shown recently that these can manifest as neonatal disorders, either hypotonia or stridor 5,6 or potentially severe episodic apnea. 7,8 In particular, de novo mutations may be responsible for severe cases with no family history.…”

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confidence: 99%

Diagnosis and Outcome of SCN4A-Related Severe Neonatal Episodic Laryngospasm (SNEL): 2 New Cases

Caietta

Milh

Sternberg³

et al. 2013

Pediatrics

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Mutations of SCN4A encoding the skeletal muscle sodium channel Nav 1.4 cause several types of disease, including sodium channel myotonias. The latter may be responsible for neonatal symptoms, including severe neonatal episodic laryngospasm (SNEL). Establishing the diagnosis of SCN4A-related SNEL early in the neonatal period is crucial because treatment is available that can reduce laryngospasm and improve vital and cerebral outcome. We report 2 new unrelated French patients who presented with SNEL. The first patient was initially diagnosed with laryngomalacia and underwent laryngeal surgery in the neonatal period before being diagnosed with myotonia at 14 months of age. The episodes of laryngospasm disappeared spontaneously, although occasional circumstances such as cold exposure could trigger laryngeal reactions; in addition, he developed myotonia corresponding to an adult myotonia permanens phenotype. This patient is now 24 years old and leading a normal life. The second patient was initially diagnosed with gastroesophageal reflux, then SNEL; his condition improved with carbamazepine treatment, and he is now 6 months old. The diagnostic sequence in both patients was the same: first, severe episodic apneic attacks necessitating hospitalization occurring in the first week of life; second, observation of muscle hypertrophy and peripheral hypertonia with a clear myotonic pattern on electromyogram (at 14 and 3 months of age, respectively); third, genetic testing revealing de novo SCN4A G1306E mutation. Both patients have had good therapeutic response to sodium channel blockers (carbamazepine or mexiletine). Pediatrics 2013;132:e784-e787 AUTHORS:

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Severe infantile hyperkalaemic periodic paralysis and paramyotonia congenita: broadening the clinical spectrum associated with the T704M mutation in SCN4A

Cited by 36 publications

References 21 publications

Severe neonatal non‐dystrophic myotonia secondary to a novel mutation of the voltage‐gated sodium channel (SCN4A) gene

Severe neonatal non‐dystrophic myotonia secondary to a novel mutation of the voltage‐gated sodium channel (SCN4A) gene

Genotype-Phenotype Correlation and Therapeutic Rationale in Hyperkalemic Periodic Paralysis

Diagnosis and Outcome of SCN4A-Related Severe Neonatal Episodic Laryngospasm (SNEL): 2 New Cases

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