Phenotypes associated with the disease neurodevelopmental disorder with hypotonia, epilepsy, and absent speech (OMIM:621455):
- Type 2 muscle fiber atrophy (HP:0003554): Atrophy (wasting) affecting primary type 2 muscle fibers. This feature in general can only be observed on muscle biopsy. Evidence: PCS. Frequency: 1/1. (PMID:27648472)
- Strabismus (HP:0000486): A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error. Evidence: PCS. Frequency: 2/2. (PMID:27648472;PMID:41125872)
- Short stature (HP:0004322): A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms). Evidence: PCS. Frequency: 3/5. (PMID:41125872)
- Hearing abnormality (HP:0000364): An abnormality of the sensory perception of sound. Evidence: PCS. Frequency: 1/1. (PMID:41125872)
- 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: PCS. Frequency: 3/3. (PMID:27648472;PMID:41125872)
- Atrophy of the spinal cord (HP:0006827). Evidence: PCS. Frequency: 1/1. (PMID:36447687)
- Profound intellectual disability (HP:0002187): Profound intellectual disability (ID) is defined as a type of ID characterized by profoundly sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) below 20. Evidence: PCS. Frequency: 3/4. (PMID:41125872)
- Abnormal circulating nitrogen compound concentration (HP:0004364): Any deviation from the normal concentration of nitrogen compound in the blood circulation. Evidence: PCS. Frequency: 0/1. (PMID:36447687)
- 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: PCS. Frequency: 7/8. (PMID:27648472;PMID:36447687;PMID:41125872)
- 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: PCS. Frequency: 3/3. (PMID:27648472;PMID:41125872)
- Multifocal epileptiform discharges (HP:0010841): An abnormality in cerebral electrical activity recorded along the scalp by electroencephalography (EEG) and being identified at multiple locations (foci). Evidence: PCS. Frequency: 1/1. (PMID:27648472)
- Short palpebral fissure (HP:0012745): Distance between the medial and lateral canthi is more than 2 SD below the mean for age (objective); or, apparently reduced length of the palpebral fissures. Evidence: PCS. Frequency: 1/1. (PMID:36447687)
- Thin corpus callosum (HP:0033725): An abnormally thin corpus callous, due to atrophy, hypoplasia or agenesis. This term is intended to be used in situations where it is not known if thinning of the corpus callosum (for instance, as visualized by magnetic resonance tomography) is due to abnormal development (e.g. a leukodystrophy) or atrophy following normal development (e.g. neurodegeneration). Evidence: PCS. Frequency: 2/5. (PMID:27648472;PMID:41125872)
- Infantile spasms (HP:0012469): Infantile spasms represent a subset of "epileptic spasms". Infantile Spasms are epileptic spasms starting in the first year of life (infancy). Evidence: PCS. Frequency: 2/4. (PMID:36447687;PMID:41125872)
- Axonal spheroids (HP:6000717): During neurodegeneration, bubble-like swellings form along the length of the axon, a primary and early effect of dynamic axonal deformation. These varicosities, spheroids, or swellings have been described as beads on a string and branches bearing fruit, and they frequently appear on degenerating axons. Evidence: PCS. Frequency: 1/1. (PMID:36447687)
- Hypertrichosis (HP:0000998): Hypertrichosis is increased hair growth that is abnormal in quantity or location. Evidence: PCS. Frequency: 1/1. (PMID:41125872)
- Kyphoscoliosis (HP:0002751): An abnormal curvature of the spine in both a coronal (lateral) and sagittal (back-to-front) plane. Evidence: PCS. Frequency: 2/2. (PMID:27648472;PMID:36447687)
- Hyporeflexia (HP:0001265): Reduction of neurologic reflexes such as the knee-jerk reaction. Evidence: PCS. Frequency: 1/1. (PMID:27648472)
- Generalized muscle weakness (HP:0003324): Generalized weakness or decreased strength of the muscles, affecting both distal and proximal musculature. Evidence: PCS. Frequency: 1/1. (PMID:36447687)
- Submucous cleft palate (HP:5201016): A cleft of the muscular portion of the palate that is covered by mucous membrane. Evidence: PCS. Frequency: 1/1. (PMID:41125872)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: PCS. Frequency: 3/3. (PMID:41125872)
- Feeding difficulties (HP:0011968): Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it. Evidence: PCS. Frequency: 1/1. (PMID:41125872)
- Poor suck (HP:0002033): An inadequate sucking reflex, resulting in the difficult of newborns to be breast-fed. Evidence: PCS. Frequency: 1/1. (PMID:36447687)
- Tetraparesis (HP:0002273): Weakness of all four limbs. Evidence: PCS. Frequency: 1/2. (PMID:41125872)
- Cough (HP:0012735): A sudden, audible expulsion of air from the lungs through a partially closed glottis, preceded by inhalation. Evidence: PCS. Frequency: 1/1. (PMID:27648472)
- Decreased compound muscle action potential amplitude (HP:0033383): Reduced level of the compound muscle action potential (CMAP), which is recorded following electrical stimulation of a nerve from surface electrodes overlying a muscle supplied by that nerve. Evidence: PCS. Frequency: 1/1. (PMID:27648472)
- Third trimester onset (HP:0034197): This term refers to a phenotypic feature that was first observed prior to birth during the third trimester, which is defined as 28 weeks and zero days (28+0) of gestation and beyond. Evidence: PCS. Frequency: 1/1. (PMID:36447687)
- 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: PCS. Frequency: 1/1. (PMID:41125872)
- Knee contracture (HP:0034671): Lack of full passive range of motion (restrictions in flexion, extension, or other movements) of the knee joint resulting from structural changes of non-bony tissues, such as muscles, tendons, ligaments, joint capsules and/or skin. Evidence: PCS. Frequency: 2/2. (PMID:27648472;PMID:41125872)
- Primary microcephaly (HP:0011451): Head circumference below 2 standard deviations below the mean for age and gender at birth. Evidence: PCS. Frequency: 0/3. (PMID:41125872)
- Hip dislocation (HP:0002827): Displacement of the femur from its normal location in the hip joint. Evidence: PCS. Frequency: 1/1. (PMID:41125872)
- Umbilical hernia (HP:0001537): Protrusion of abdominal contents through a defect in the abdominal wall musculature around the umbilicus. Skin and subcutaneous tissue overlie the defect. Evidence: PCS. Frequency: 2/2. (PMID:36447687;PMID:41125872)
- Autosomal recessive inheritance (HP:0000007): A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). Evidence: PCS. (PMID:41125872)
- Thoracolumbar scoliosis (HP:0002944). Evidence: PCS. Frequency: 2/2. (PMID:41125872)
- Clinodactyly of the 5th finger (HP:0004209): Clinodactyly refers to a bending or curvature of the fifth finger in the radial direction (i.e., towards the 4th finger). Evidence: PCS. Frequency: 1/1. (PMID:27648472)
- 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: PCS. Frequency: 1/1. (PMID:41125872)
- Patent foramen ovale (HP:0001655): Failure of the foramen ovale to seal postnatally, leaving a potential conduit between the left and right cardiac atria. Evidence: PCS. Frequency: 1/1. (PMID:41125872)
- Hypertonia (HP:0001276): A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move. Evidence: PCS. Frequency: 2/7. (PMID:36447687;PMID:41125872)
- Narrow forehead (HP:0000341): Width of the forehead or distance between the frontotemporales is more than two standard deviations below the mean (objective); or apparently narrow intertemporal region (subjective). Evidence: PCS. Frequency: 2/2. (PMID:27648472;PMID:36447687)
- Hypsarrhythmia (HP:0002521): Hypsarrhythmia is abnormal interictal high amplitude waves and a background of irregular spikes. There is continuous (during wakefulness), high-amplitude (>200 Hz), generalized polymorphic slowing with no organized background and multifocal spikes demonstrated by electroencephalography (EEG). Evidence: PCS. Frequency: 1/3. (PMID:41125872)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 1/1. (PMID:27648472)
- Inguinal hernia (HP:0000023): Protrusion of the contents of the abdominal cavity through the inguinal canal. Evidence: PCS. Frequency: 1/1. (PMID:41125872)
- Anteverted nares (HP:0000463): Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip). Evidence: PCS. Frequency: 1/1. (PMID:36447687)
- Generalized osteoporosis (HP:0040160). Evidence: PCS. Frequency: 1/1. (PMID:41125872)
- Intrahepatic inclusion bodies (HP:6000976): Nuclear or cytoplasmic aggregates of stainable substances within hepatocytes. Evidence: PCS. Frequency: 1/1. (PMID:36447687)
- Motor delay (HP:0001270): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: PCS. Frequency: 1/1. (PMID:41125872)
- Aspiration pneumonia (HP:0011951): Pneumonia due to the aspiration (breathing in) of food, liquid, or gastric contents into the upper respiratory tract. Evidence: PCS. Frequency: 1/1. (PMID:27648472)
- Severe intellectual disability (HP:0010864): Severe intellectual disability (ID) is defined as a type of ID characterized by severely sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) the range of 20-34. Evidence: PCS. Frequency: 1/4. (PMID:41125872)
- Osteoporosis (HP:0000939): Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD). Evidence: PCS. Frequency: 1/1. (PMID:41125872)
- Irritability (HP:0000737): An emotional state characterized by negative feelings of heightened frustration, annoyance, or feeling upset, often triggered by internal factors (e.g., fatigue, hunger, unfulfilled desires) or external factors (e.g., social or environmental challenges). Irritability may be unpredictable, and is accompanied by a lowered threshold for emotional reactivity and observable features (speech, facial expressions, or psychomotor activity). Evidence: PCS. Frequency: 1/1. (PMID:36447687)
- Osteopenia (HP:0000938): Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5. Evidence: PCS. Frequency: 1/1. (PMID:41125872)
- Hip subluxation (HP:0030043): A partial dislocation of the hip joint, whereby the head of the femur is partially displaced from the socket. Evidence: PCS. Frequency: 1/1. (PMID:41125872)
- Respiratory failure (HP:0002878): A severe form of respiratory insufficiency characterized by inadequate gas exchange such that the levels of oxygen or carbon dioxide cannot be maintained within normal limits. Evidence: PCS. Frequency: 2/2. (PMID:27648472;PMID:41125872)
- Fetal distress (HP:0025116): An intrauterine state characterized by suboptimal values in the fetal heart rate, oxygenation of fetal blood, or other parameters indicative of compromise of the fetus. Signs of fetal distress include repetitive variable decelerations, fetal tachycardia or bradycardia, late decelerations, or low biophysical profile. Evidence: PCS. Frequency: 1/1. (PMID:27648472)
- Type 1 muscle fiber predominance (HP:0003803): An abnormal predominance of type I muscle fibers (in general, this feature can only be observed on muscle biopsy). Evidence: PCS. Frequency: 1/1. (PMID:27648472)
- 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: PCS. Frequency: 1/1. (PMID:27648472)
- Ventilator dependence with inability to wean (HP:0005946). Evidence: PCS. Frequency: 1/1. (PMID:27648472)
- Premature rupture of membranes (HP:0001788): Premature rupture of membranes (PROM) is a condition which occurs in pregnancy when the amniotic sac ruptures more than an hour before the onset of labor. Evidence: PCS. Frequency: 1/1. (PMID:27648472)
- Congenital diaphragmatic hernia (HP:0000776): The presence of a hernia of the diaphragm present at birth. Evidence: PCS. Frequency: 1/1. (PMID:36447687)
- EMG: decremental response of compound muscle action potential to repetitive nerve stimulation (HP:0003403): A compound muscle action potential (CMAP) is a type of electromyography (EMG). CMAP refers to a group of almost simultaneous action potentials from several muscle fibers in the same area evoked by stimulation of the supplying motor nerve and are recorded as one multipeaked summated action potential. This abnormality refers to a greater than normal decrease in the amplitude during the course of the investigation. Evidence: PCS. Frequency: 2/2. (PMID:27648472;PMID:41125872)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: PCS. Frequency: 1/1. (PMID:41125872)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: PCS. Frequency: 3/3. (PMID:41125872)
- Delayed speech and language development (HP:0000750): A degree of language development that is significantly below the norm for a child of a specified age. Evidence: PCS. Frequency: 3/3. (PMID:41125872)
- Wide nasal bridge (HP:0000431): Increased breadth of the nasal bridge (and with it, the nasal root). Evidence: PCS. Frequency: 1/1. (PMID:27648472)
- Delayed ability to walk (HP:0031936): A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months. Evidence: PCS. Frequency: 5/5. (PMID:41125872)
- Asthma (HP:0002099): Asthma is characterized by increased responsiveness of the tracheobronchial tree to multiple stimuli, leading to narrowing of the air passages with resultant dyspnea, cough, and wheezing. Evidence: PCS. Frequency: 1/1. (PMID:41125872)
- Episodic vomiting (HP:0002572): Paroxysmal, recurrent episodes of vomiting. Evidence: PCS. Frequency: 1/1. (PMID:27648472)
- Secondary microcephaly (HP:0005484): Head circumference which falls below 2 standard deviations below the mean for age and gender because of insufficient head growth after birth. Evidence: PCS. Frequency: 3/6. (PMID:27648472;PMID:41125872)
- Areflexia (HP:0001284): Absence of neurologic reflexes such as the knee-jerk reaction. Evidence: PCS. Frequency: 1/2. (PMID:41125872)
- Gliosis (HP:0002171): Gliosis is the focal proliferation of glial cells in the central nervous system. Evidence: PCS. Frequency: 1/1. (PMID:36447687)
- Bilateral tonic-clonic seizure with generalized onset (HP:0025190): A bilateral tonic-clonic seizure with generalized onset is a type of bilateral tonic-clonic seizure characterized by generalized onset; these seizures rapidly engage networks in both hemispheres at the start of the seizure. Evidence: PCS. Frequency: 2/3. (PMID:41125872)
- EEG with burst suppression (HP:0010851): The burst suppression pattern in electroencephalography refers to a characteristic periodic pattern of low voltage (<10 microvolts) suppressed background and a relatively shorter pattern of higher amplitude slow, sharp, and spiking complexes. Evidence: PCS. Frequency: 1/1. (PMID:36447687)
- Restrictive ventilatory defect (HP:0002091): A functional defect characterized by reduced total lung capacity (TLC) not associated with abnormalities of expiratory airflow or airway resistance. Spirometrically, a restrictive defect is defined as FEV1 (forced expiratory volume in 1 second) and FVC (forced vital capacity) less than 80 per cent. Restrictive lung disease may be caused by alterations in lung parenchyma or because of a disease of the pleura, chest wall, or neuromuscular apparatus. Evidence: PCS. Frequency: 1/1. (PMID:41125872)
- 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: PCS. Frequency: 1/2. (PMID:27648472;PMID:41125872)
- High forehead (HP:0000348): An abnormally increased height of the forehead. Evidence: PCS. Frequency: 1/1. (PMID:27648472)
- Decreased fetal movement (HP:0001558): An abnormal reduction in quantity or strength of fetal movements. Evidence: PCS. Frequency: 1/1. (PMID:36447687)
- Epileptic encephalopathy (HP:0200134): A condition in which epileptiform abnormalities are believed to contribute to the progressive disturbance in cerebral function. Epileptic encephalaopathy is characterized by (1) electrographic EEG paroxysmal activity that is often aggressive, (2) seizures that are usually multiform and intractable, (3) cognitive, behavioral and neurological deficits that may be relentless, and (4) sometimes early death. Evidence: PCS. Frequency: 1/4. (PMID:41125872)
- Recurrent respiratory infections (HP:0002205): An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections. Evidence: PCS. Frequency: 1/1. (PMID:41125872)
- Cryptorchidism (HP:0000028): Testis in inguinal canal. That is, absence of one or both testes from the scrotum owing to failure of the testis or testes to descend through the inguinal canal to the scrotum. Evidence: PCS. Frequency: 1/1. (PMID:41125872)
- EMG: myopathic abnormalities (HP:0003458): The presence of abnormal electromyographic patterns indicative of myopathy, such as small-short polyphasic motor unit potentials. Evidence: PCS. Frequency: 1/1. (PMID:41125872)