- Joint hypermobility (HP:0001382): The capability that a joint (or a group of joints) has to move, passively and/or actively, beyond normal limits along physiological axes. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:98914)
- Gait disturbance (HP:0001288): The term gait disturbance can refer to any disruption of the ability to walk. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:98914)
- Neck muscle weakness (HP:0000467): Decreased strength of the neck musculature. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:98914)
- Ptosis (HP:0000508): The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective). Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:98914)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:98914)
- Poor suck (HP:0002033): An inadequate sucking reflex, resulting in the difficult of newborns to be breast-fed. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:98914)
- Sudden episodic apnea (HP:0002882): Recurrent bouts of sudden, severe apnea that may be life-threatening. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:98914)
- Fatigable weakness (HP:0003473): A type of weakness that occurs after a muscle group is used and lessens if the muscle group has some rest. That is, there is diminution of strength with repetitive muscle actions. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:98914)
- Proximal muscle weakness (HP:0003701): A lack of strength of the proximal muscles. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:98914)
- Frontalis muscle weakness (HP:0004661): Reduced strength of the frontalis muscle (which is located on the forehead). Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:98914)
- Intermittent episodes of respiratory insufficiency due to muscle weakness (HP:0004889). Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:98914)
- Feeding difficulties (HP:0011968): Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:98914)
- Ophthalmoplegia (HP:0000602): Paralysis of one or more extraocular muscles that are responsible for eye movements. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:98914)
- Cyanosis (HP:0000961): Bluish discoloration of the skin and mucosa due to poor circulation or inadequate oxygenation of arterial or capillary blood. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:98914)
- Intellectual disability (HP:0001249): The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:98914)
- Ataxia (HP:0001251): Ataxia refers to impaired coordination of voluntary muscle movement. Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:98914)
- Bulbar palsy (HP:0001283): Bulbar weakness (or bulbar palsy) refers to bilateral impairment of function of the lower cranial nerves IX, X, XI and XII, which occurs due to lower motor neuron lesion either at nuclear or fascicular level in the medulla or from bilateral lesions of the lower cranial nerves outside the brain-stem. Bulbar weakness is often associated with difficulty in chewing, weakness of the facial muscles, dysarthria, palatal weakness and regurgitation of fluids, dysphagia, and dysphonia. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:98914)
- Decreased fetal movement (HP:0001558): An abnormal reduction in quantity or strength of fetal movements. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:98914)
- Hypernasal speech (HP:0001611): A type of speech characterized by the presence of an abnormally increased nasal airflow during speech associated with structural abnormality of the nasal passages. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:98914)
- Recurrent respiratory infections (HP:0002205): An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:98914)
- Arthrogryposis multiplex congenita (HP:0002804): Multiple congenital contractures in different body areas. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:98914)
- Apneic episodes precipitated by illness, fatigue, stress (HP:0002872): Recurrent episodes of apnea that are precipitated by factors such as illness, fatigue, or stress. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:98914)
- Generalized muscle weakness (HP:0003324): Generalized weakness or decreased strength of the muscles, affecting both distal and proximal musculature. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:98914)
- Easy fatigability (HP:0003388): Increased susceptibility to fatigue. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:98914)
- Episodic respiratory distress (HP:0004885). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:98914)
- Neuropathic spinal arthropathy (HP:0008443): A progressive disorder of vertebral joint degeneration that occurs in the setting of any condition characterized by decreased afferent innervation, involving loss of deep pain and proprioceptive sensation in the vertebral column. Patients most commonly present with symptoms of lower back pain, sitting imbalance, progressive spinal deformity (usually kyphosis), and an audible clicking sound on changing postures. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:98914)
- Central sleep apnea (HP:0010536): Sleep apnea results from a temporary loss of the central drive to the muscles responsible for breathing. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:98914)
- Nasal regurgitation (HP:0011469): Regurgitation of milk through the nose. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:98914)
- Choking episodes (HP:0030842): Incidents in which a piece of food or other objects get stuck in the upper airway and provoke coughing, gagging, inability to talk, and difficulty breathing. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:98914)
- EMG: impaired neuromuscular transmission (HP:0100285): An electromyographic finding associated with erratic or absent neuromuscular transmission with erratic, moment-to-moment changes in the shape of the motor unit potential (MUP). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:98914)
- Muscle fiber atrophy (HP:0100295). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:98914)
- High palate (HP:0000218): Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98914)
- Long face (HP:0000276): Facial height (length) is more than 2 standard deviations above the mean (objective); or, an apparent increase in the height (length) of the face (subjective). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98914)
- Seizure (HP:0001250): A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98914)
- Hypotonia (HP:0001252): Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98914)
- Motor delay (HP:0001270): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98914)
- Areflexia (HP:0001284): Absence of neurologic reflexes such as the knee-jerk reaction. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98914)
- Weak cry (HP:0001612). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98914)
- Dysphonia (HP:0001618): Difficulty in speaking due to a physical disorder of the mouth, tongue, throat, or vocal cords. Associated with a known physical or neurological cause. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98914)
- Pes cavus (HP:0001761): An increase in height of the medial longitudinal arch of the foot that does not flatten on weight bearing (i.e., a distinctly hollow form of the sole of the foot when it is bearing weight). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98914)
- Poor head control (HP:0002421): Difficulty to maintain correct position of the head while standing or sitting. Infant head lag is observed when the head seems to flop around or lags posteriorly behind the trunk. Several articles have maintained that head lag should be absent by age 3 to 4 months. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98914)
- Waddling gait (HP:0002515): Weakness of the hip girdle and upper thigh muscles, for instance in myopathies, leads to an instability of the pelvis on standing and walking. If the muscles extending the hip joint are affected, the posture in that joint becomes flexed and lumbar lordosis increases. The patients usually have difficulties standing up from a sitting position. Due to weakness in the gluteus medius muscle, the hip on the side of the swinging leg drops with each step (referred to as Trendelenburg sign). The gait appears waddling. The patients frequently attempt to counteract the dropping of the hip on the swinging side by bending the trunk towards the side which is in the stance phase (in the German language literature this is referred to as Duchenne sign). Similar gait patterns can be caused by orthopedic conditions when the origin and the insertion site of the gluteus medius muscle are closer to each other than normal, for instance due to a posttraumatic elevation of the trochanter or pseudarthrosis of the femoral neck. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98914)
- Kyphoscoliosis (HP:0002751): An abnormal curvature of the spine in both a coronal (lateral) and sagittal (back-to-front) plane. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98914)
- Spinal rigidity (HP:0003306): Reduced ability to move the vertebral column with a resulting limitation of neck and trunk flexion. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98914)
- Limb-girdle muscle weakness (HP:0003325): Weakness of the limb-girdle muscles (also known as the pelvic and shoulder girdles), that is, lack of strength of the muscles around the shoulders and the pelvis. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98914)
- EMG: myopathic abnormalities (HP:0003458): The presence of abnormal electromyographic patterns indicative of myopathy, such as small-short polyphasic motor unit potentials. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98914)
- Distal amyotrophy (HP:0003693): Muscular atrophy affecting muscles in the distal portions of the extremities. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98914)
- Distal lower limb muscle weakness (HP:0009053): Reduced strength of the distal musculature of the legs. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98914)
- Stridor (HP:0010307): Stridor is a high pitched sound resulting from turbulent air flow in the upper airway. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98914)
- Narrow jaw (HP:0012801): Bigonial distance (lower facial width) more than 2 standard deviations below the mean (objective); or an apparently decreased width of the lower jaw (mandible) when viewed from the front (subjective). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98914)
- Tip-toe gait (HP:0030051): An abnormal gait pattern characterized by the failure of the heel to contact the floor at the onset of stance during gait. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98914)
- Microretrognathia (HP:0000308): A form of developmental hypoplasia of the mandible in which the mandible is mislocalised posteriorly. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:98914)
- Low-set ears (HP:0000369): Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:98914)
- Sensorineural hearing impairment (HP:0000407): A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:98914)
- Esotropia (HP:0000565): A form of strabismus with one or both eyes turned inward ('crossed') to a relatively severe degree, usually defined as 10 diopters or more. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:98914)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:98914)
- Diplopia (HP:0000651): Diplopia is a condition in which a single object is perceived as two images, it is also known as double vision. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:98914)
- Pectus carinatum (HP:0000768): A deformity of the chest caused by overgrowth of the ribs and characterized by protrusion of the sternum. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:98914)
- Hyporeflexia (HP:0001265): Reduction of neurologic reflexes such as the knee-jerk reaction. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:98914)
- Congenital hip dislocation (HP:0001374). Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:98914)
- Polyhydramnios (HP:0001561): The presence of excess amniotic fluid in the uterus during pregnancy. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:98914)
- Gastroesophageal reflux (HP:0002020): A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:98914)
- EEG with polyspike wave complexes (HP:0002392): The presence of complexes of repetitive spikes and waves in EEG. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:98914)
- Obstructive sleep apnea (HP:0002870): Obstructive Sleep Apnea is a condition characterized by the obstruction of the airway and pauses in breathing during sleep, which occur multiple times throughout the night. It is related to the relaxation of muscle tone that typically happens during sleep, leading to a partial collapse of the soft tissues in the airway and causing airflow obstruction. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:98914)
- Respiratory arrest (HP:0005943). Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:98914)
- Motor polyneuropathy (HP:0007178). Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:98914)
- Staring gaze (HP:0025401): An abnormality in which the eyes are held permanently wide open. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:98914)
These phenotypes are associated with the disease Presynaptic congenital myasthenic syndromes (ORPHA:98914).
The following phenotypes are NOT associated with this disease:
- Anti-neuromuscular Junction acetylcholine receptor antibody positivity (HP:0030208): The presence of autoantibodies (immunoglobulins) in the blood circulation that react against neuromuscular junction acetylcholine receptors. Evidence: TAS. (ORPHA:98914)