227-305 (Predicted disordered autoinhibitory region)

[MIM: 616325]: Myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency (CMS9)

A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS9 is a disorder of postsynaptic neuromuscular transmission, due to deficiency of AChR at the endplate that results in low amplitude of the miniature endplate potential and current. {ECO:0000269|PubMed:15496425, ECO:0000269|PubMed:19949040, ECO:0000269|PubMed:20371544, ECO:0000269|PubMed:23326516, ECO:0000269|PubMed:24183479}. Note=The disease is caused by variants affecting the gene represented in this entry. MUSK mutations lead to decreased agrin-dependent AChR aggregation, a critical step in the formation of the neuromuscular junction.

[MIM: 208150]: Fetal akinesia deformation sequence 1 (FADS1)

A clinically and genetically heterogeneous group of disorders with congenital malformations related to impaired fetal movement. Clinical features include fetal akinesia, intrauterine growth retardation, polyhydramnios, arthrogryposis, pulmonary hypoplasia, craniofacial abnormalities, and cryptorchidism. FADS1 inheritance is autosomal recessive. {ECO:0000269|PubMed:25537362, ECO:0000269|PubMed:25612909}. Note=The disease is caused by variants affecting the gene represented in this entry.

Without disease ID

• A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS9 is a disorder of postsynaptic neuromuscular transmission, due to deficiency of AChR at the endplate that results in low amplitude of the miniature endplate potential and current. {ECO:0000269|PubMed:15496425, ECO:0000269|PubMed:19949040, ECO:0000269|PubMed:20371544, ECO:0000269|PubMed:23326516, ECO:0000269|PubMed:24183479}. Note=The disease is caused by variants affecting the gene represented in this entry. MUSK mutations lead to decreased agrin-dependent AChR aggregation, a critical step in the formation of the neuromuscular junction.
• A clinically and genetically heterogeneous group of disorders with congenital malformations related to impaired fetal movement. Clinical features include fetal akinesia, intrauterine growth retardation, polyhydramnios, arthrogryposis, pulmonary hypoplasia, craniofacial abnormalities, and cryptorchidism. FADS1 inheritance is autosomal recessive. {ECO:0000269|PubMed:25537362, ECO:0000269|PubMed:25612909}. Note=The disease is caused by variants affecting the gene represented in this entry.