COLQ-mutant congenital myasthenic syndrome with microcephaly: A unique case with literature review

Al–Muhaizea, Mohammad A.; Almobarak, Sulaiman

doi:10.1515/tnsci-2017-0011

Cited by 6 publications

(9 citation statements)

References 20 publications

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“…The pupillary response may be slowed. Some patients may present with respiratory failure at birth or later in the course [41, 42]. Some patients may present with severe scoliosis [43].…”

Section: Resultsmentioning

confidence: 99%

“…In two patients, isolated vocal cord paralysis has been reported as initial manifestation, which did not respond to pyridostigmine, mildly to 3,4-DAP, but favourably to ephedrine [42]. Rarely, microcephaly has been reported [41]. Interestingly, heterozygote carriers can present with congenital ptosis [44].…”

Section: Resultsmentioning

confidence: 99%

“…These include long face ( SYB1 ) [7], hypertelorism ( SYB1 ) [7], narrow jaw ( RAPSN ), saddle nose ( SYB1 ) [7], and high-arched palate ( SCN4A ) [96]. In a Saudi female carrying a COLQ mutation, microcephaly was reported (Table 3) [41]. Microcephaly was also reported in MUNC13–1 -related CMS.…”

Section: Resultsmentioning

confidence: 99%

“…Foot deformities include pes cavus (hollow foot), pes planus, or hammertoes ( SYT2 -related CMS [127], SLC25A1 ). Club feet have been found in RAPSN -related CMS [54], and COLQ -related CMS [41]. In SCN4A -related CMS adduction deformity of the knees and ankles were reported [96].…”

Section: Resultsmentioning

confidence: 99%

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Congenital myasthenic syndromes

Finsterer

2019

Orphanet J Rare Dis

138

154

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Objectives Congenital myasthenic syndromes (CMSs) are a genotypically and phenotypically heterogeneous group of neuromuscular disorders, which have in common an impaired neuromuscular transmission. Since the field of CMSs is steadily expanding, the present review aimed at summarizing and discussing current knowledge and recent advances concerning the etiology, clinical presentation, diagnosis, and treatment of CMSs. Methods Systematic literature review. Results Currently, mutations in 32 genes are made responsible for autosomal dominant or autosomal recessive CMSs. These mutations concern 8 presynaptic, 4 synaptic, 15 post-synaptic, and 5 glycosilation proteins. These proteins function as ion-channels, enzymes, or structural, signalling, sensor, or transporter proteins. The most common causative genes are CHAT, COLQ, RAPSN, CHRNE, DOK7, and GFPT1. Phenotypically, these mutations manifest as abnormal fatigability or permanent or fluctuating weakness of extra-ocular, facial, bulbar, axial, respiratory, or limb muscles, hypotonia, or developmental delay. Cognitive disability, dysmorphism, neuropathy, or epilepsy are rare. Low- or high-frequency repetitive nerve stimulation may show an abnormal increment or decrement, and SF-EMG an increased jitter or blockings. Most CMSs respond favourably to acetylcholine-esterase inhibitors, 3,4-diamino-pyridine, salbutamol, albuterol, ephedrine, fluoxetine, or atracurium. Conclusions CMSs are an increasingly recognised group of genetically transmitted defects, which usually respond favorably to drugs enhancing the neuromuscular transmission. CMSs need to be differentiated from neuromuscular disorders due to muscle or nerve dysfunction.

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“…The pupillary response may be slowed. Some patients may present with respiratory failure at birth or later in the course [41, 42]. Some patients may present with severe scoliosis [43].…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Congenital myasthenic syndromes

Finsterer

2019

Orphanet J Rare Dis

138

154

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“…In the neonatal period, the main symptoms are dystonia, ptosis, eye paralysis, respiratory insufficiency, and even respiratory failure due to respiratory muscle weakness ( 14 ). Microcephaly has been reported in a few cases ( 15 ) and generally does not affect cognition ( 1 ). Movement development is difficult, and patients show delayed head support, sitting up, and walking, with a tendency to fall when walking.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of Congenital Myasthenia Caused by Three Mutations in the COLQ Gene

et al. 2021

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The gene encoding collagen like tail subunit of asymmetric acetylcholinesterase (COLQ) is responsible for the transcription of three strands of collagen of acetylcholinesterase, which is attached to the endplate of neuromuscular junctions. Mutations in the COLQ gene are inherited in an autosomal-recessive manner and can lead to type V congenital myasthenia syndrome (CMS), which manifests as decreased muscle strength at birth or shortly after birth, respiratory failure, restricted eye movements, drooping of eyelids, and difficulty swallowing. Here we reported three variants within COLQ in two unrelated children with CMS. An intronic variant (c.393+1G>A) and a novel missense variant (p.Q381P) were identified as compound heterozygous in a 13-month-old boy, with the parents being carriers of each. An intragenic deletion including exons 14 and 15 was found in a homozygous state in a 12-year-old boy. We studied the relative expression of the COLQ and AChE gene in the probands' families, performed three-dimensional protein structural analysis, and analyzed the conservation of the missense mutation c.1142A>C (p.Q381P). The splicing mutation c.393+1G>A was found to affect the normal splicing of COLQ exon 5, resulting in a 27-bp deletion. The missense mutation c.1142A>C (p.Q381P) was located in a conserved position in different species. We found that homozygous deletion of COLQ exons 14–15 resulted in a 241-bp deletion, which decreased the number of amino acids and caused a frameshift translation. COLQ expression was significantly lower in the probands than in the probands' parents and siblings, while AChE expression was significantly higher. Moreover, the mutations were found to cause significant differences in the predicted three-dimensional structure of the protein. The splicing mutation c.393+1G>A, missense mutation c.1A>C (p.Q381P), and COLQ exon 14–15 deletion could cause CMS.

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