Muscular hypotonia, and Respiratory insufficiency

Congenital myasthenic syndrome associated with AChR deficiency is a disorder of the postsynaptic neuromuscular junction (NMJ) characterized clinically by early-onset muscle weakness with variable severity. Electrophysiologic studies show low amplitude of the miniature endplate potential (MEPP) and current (MEPC) resulting from deficiency of AChR at the endplate. Treatment with cholinesterase inhibitors or amifampridine may be helpful (summary by Engel et al., 2015).For a discussion of genetic heterogeneity of CMS, see CMS1A (OMIM ).

• Muscle weakness
• Feeding difficulties
• Respiratory insufficiency
• Myopathy
• Neonatal hypotonia

SOURCES: OMIM MENDELIAN

Congenital myasthenic syndrome associated with AChR deficiency is a disorder of the postsynaptic neuromuscular junction (NMJ) clinically characterized by early-onset muscle weakness with variable severity. Electrophysiologic studies show low amplitude of the miniature endplate potential (MEPP) and current (MEPC) resulting from deficiency of AChR at the endplate. Treatment with acetylcholinesterase inhibitors or amifampridine may be helpful (summary by Engel et al., 2015).For a discussion of genetic heterogeneity of CMS, see CMS1A (OMIM ).

• Generalized hypotonia
• Muscle weakness
• Ptosis
• High palate
• Feeding difficulties

SOURCES: OMIM MENDELIAN

MTDPS12A is characterized by severe hypotonia due to mitochondrial dysfunction apparent at birth. Affected infants have respiratory insufficiency requiring mechanical ventilation and have poor or no motor development. Many die in infancy, and those that survive have profound hypotonia with significant muscle weakness and inability to walk independently. Some patients develop hypertrophic cardiomyopathy. Muscle samples show mtDNA depletion and severe combined mitochondrial respiratory chain deficiencies (summary by Thompson et al., 2016).For a discussion of genetic heterogeneity of mtDNA depletion syndromes, see MTDPS1 (OMIM ).

• Seizures
• Generalized hypotonia
• Muscle weakness
• Respiratory insufficiency
• Cardiomyopathy

SOURCES: OMIM MENDELIAN

Pyruvate dehydrogenase E1-beta deficiency is an extremely rare form of pyruvate dehydrogenase deficiency (PDHD, see this term) characterized by severe lactic acidosis, developmental delay and hypotonia.

PYRUVATE DEHYDROGENASE E1-BETA DEFICIENCY Is also known as pdhbd|pyruvate dehydrogenase complex e1 component subunit beta deficiency

• Generalized hypotonia
• Agenesis of corpus callosum
• Acidosis
• Lactic acidosis
• Metabolic acidosis

SOURCES: OMIM ORPHANET MESH MENDELIAN

Pyridoxine-dependent epilepsy, characterized by a combination of various seizure types, usually occurs in the first hours of life and is unresponsive to standard anticonvulsants, responding only to immediate administration of pyridoxine hydrochloride. The dependence is permanent, and the interruption of daily pyridoxine supplementation leads to the recurrence of seizures. Some patients show developmental delay. The prevalence is estimated at 1 in 400,000 to 700,000 (Bennett et al., 2005).

EPILEPSY, PYRIDOXINE-DEPENDENT; EPD Is also known as pyridoxine dependency with seizures|pde|pyridoxine-dependent epilepsy|aasa dehydrogenase deficiency

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Muscular hypotonia

SOURCES: OMIM MENDELIAN

Fast-channel congenital myasthenic syndrome (FCCMS) is a disorder of the postsynaptic neuromuscular junction (NMJ) characterized by early-onset progressive muscle weakness. The disorder results from kinetic abnormalities of the AChR channel, specifically from abnormally brief opening and activity of the channel, with a rapid decay in endplate current and a failure to reach the threshold for depolarization. Treatment with pyridostigmine or amifampridine may be helpful; quinine, quinidine, and fluoxetine should be avoided (summary by Sine et al., 2003 and Engel et al., 2015).For a discussion of genetic heterogeneity of CMS, see CMS1A (OMIM ).

• Muscle weakness
• Ptosis
• Feeding difficulties
• Respiratory insufficiency
• Neonatal hypotonia

SOURCES: OMIM MENDELIAN

Slow-channel congenital myasthenic syndrome (SCCMS) is a disorder of the postsynaptic neuromuscular junction (NMJ) characterized by early-onset progressive muscle weakness. The disorder results from kinetic abnormalities of the AChR channel, specifically from prolonged opening and activity of the channel, which causes prolonged synaptic currents resulting in a depolarization block. This is associated with calcium overload, which may contribute to subsequent degeneration of the endplate and postsynaptic membrane. Treatment with quinine, quinidine, or fluoxetine may be helpful; acetylcholinesterase inhibitors and amifampridine should be avoided (summary by Engel et al., 2015).For a discussion of genetic heterogeneity of CMS, see CMS1A (OMIM ).

• Muscle weakness
• Ptosis
• Motor delay
• Dysphagia
• Respiratory insufficiency

SOURCES: OMIM MENDELIAN

Paramyotonia congenita of Von Eulenburg is characterised by exercise- or cold-induced myotonia and muscle weakness. Prevalence is unknown. The syndrome is nonprogressive and is transmitted as an autosomal dominant trait. It is caused by mutations in the gene encoding the alpha subunit of the type IV voltage-gated sodium channel (SCN4A; 17q23.3).

PARAMYOTONIA CONGENITA OF VON EULENBURG Is also known as paramyotonia congenita

• Feeding difficulties
• Dysphagia
• Neonatal hypotonia
• Myalgia
• Muscle stiffness

SOURCES: ORPHANET MENDELIAN

Slow-channel congenital myasthenic syndrome (SCCMS) is a disorder of the postsynaptic neuromuscular junction (NMJ) characterized by early-onset progressive muscle weakness. The disorder results from kinetic abnormalities of the acetylcholine receptor channel, specifically from prolonged opening and activity of the channel, which causes prolonged synaptic currents resulting in a depolarization block. This is associated with calcium overload, which may contribute to subsequent degeneration of the endplate and postsynaptic membrane. Treatment with quinine, quinidine, or fluoxetine may be helpful; acetylcholinesterase inhibitors and amifampridine should be avoided (summary by Engel et al., 2015).For a discussion of genetic heterogeneity of CMS, see CMS1A (OMIM ).

MYASTHENIC SYNDROME, CONGENITAL, 4A, SLOW-CHANNEL; CMS4A Is also known as cms1a1, formerly|cms ia1, formerly|congenital myasthenic syndrome type ia1, formerly

• Generalized hypotonia
• Strabismus
• Muscle weakness
• Ptosis
• Dysphagia

SOURCES: OMIM MENDELIAN

Central core disease (CCD) is an inherited neuromuscular disorder characterised by central cores on muscle biopsy and clinical features of a congenital myopathy.

• Muscular hypotonia
• Motor delay
• Talipes equinovarus
• Myopathy
• Elevated serum creatine phosphokinase

SOURCES: ORPHANET MENDELIAN