Phenotypes associated with the disease multiple congenital anomalies-hypotonia-seizures syndrome 2 (OMIM:300868):
- Encephalopathy (HP:0001298): Encephalopathy is a term that means brain disease, damage, or malfunction. In general, encephalopathy is manifested by an altered mental state. Evidence: PCS. Frequency: 2/2. (PMID:24259288)
- Exaggerated startle response (HP:0002267): An exaggerated startle reaction in response to a sudden unexpected visual or acoustic stimulus, or a quick movement near the face. Evidence: PCS. Frequency: 1/1. (PMID:25885527)
- Stomatocytosis (HP:0004446): The presence of erythrocytes with a mouth-shaped (stoma) area of central pallor on peripheral blood smear. Evidence: PCS. Frequency: 1/1. (PMID:25885527)
- Focal clonic seizure (HP:0002266): A focal clonic seizure is a type of focal motor seizure characterized by sustained rhythmic jerking, that is regularly repetitive. Evidence: PCS. Frequency: 1/1. (PMID:24259184)
- 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: 1/1. (PMID:24259288)
- Seborrheic dermatitis (HP:0001051): Seborrheic dermatitis is a form of eczema which is closely related to dandruff. It causes dry or greasy peeling of the scalp, eyebrows, and face, and sometimes trunk. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:300868)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 10/10. (PMID:24259288;PMID:29502866;PMID:24357517)
- 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:25885527)
- Starry sky appearance on hepatic sonography (HP:0031145): An abnormal echotexture visible in liver ultrasound manifesting as a diffuse hyperechoic liver echotexture with multiple, small hypoechoic lesions. The appearance is said to resemble a starry sky (multiple white spots on a dark background). Evidence: PCS. Frequency: 1/1. (PMID:25885527)
- Duplicated collecting system (HP:0000081): A duplication of the collecting system of the kidney, defined as a kidney with two (instead of, normally, one) pyelocaliceal systems. The pyelocaliceal system is comprised of the renal pelvis and calices. The duplicated renal collecting system can be associated with a single ureter or with double ureters. In the latter case, the two ureters empty separately into the bladder or fuse to form a single ureteral orifice. Evidence: PCS. Frequency: 1/2. (PMID:22305531)
- Deep palmar crease (HP:0006191): Excessively deep creases of the palm. Evidence: PCS. Frequency: 1/1. (PMID:25885527)
- Long palpebral fissure (HP:0000637): Distance between medial and lateral canthi is more than two standard deviations above the mean for age (objective); or, apparently increased length of the palpebral fissures. Evidence: PCS. Frequency: 1/1. (PMID:25885527)
- Diffuse leukoencephalopathy (HP:0006994). Evidence: PCS. Frequency: 1/1. (PMID:25885527)
- Arrhinencephaly (HP:0002139): A defect of development of the brain characterized by congenital absence of the part of the brain that includes the olfactory bulbs, tracts, and other structures associated with the sense of smell. Evidence: PCS. Frequency: 1/1. (PMID:22305531)
- Broad palm (HP:0001169): For children from birth to 4 years of age the palm width is more than 2 SD above the mean; for children from 4 to 16 years of age the palm width is above the 95th centile; or, the width of the palm appears disproportionately wide for the length. Evidence: PCS. Frequency: 1/2. (PMID:22305531)
- Babinski sign (HP:0003487): Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract. Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Limb joint contracture (HP:0003121): A contracture (chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin) that prevent normal movement of one or more joints of the limbs. Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Profound global developmental delay (HP:0012736): A profound delay in the achievement of motor or mental milestones in the domains of development of a child. Evidence: PCS. Frequency: 1/1. (PMID:25885527)
- Tapered finger (HP:0001182): The gradual reduction in girth of the finger from proximal to distal. Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- High, narrow palate (HP:0002705): The presence of a high and narrow palate. Evidence: PCS. Frequency: 2/2. (PMID:25885527;PMID:22305531)
- Upper limb spasticity (HP:0006986). Evidence: TAS. (OMIM:300868)
- Hepatic steatosis (HP:0001397): Steatosis is a term used to denote lipid accumulation within hepatocytes. Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 3/3. (PMID:25885527;PMID:22305531)
- Hepatic failure (HP:0001399). Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Generalized myoclonic seizure (HP:0002123): A generalized myoclonic seizure is a type of generalized motor seizure characterized by bilateral, sudden, brief (<100 ms) involuntary single or multiple contraction of muscles or muscle groups of variable topography (axial, proximal limb, distal). Myoclonus is less regularly repetitive and less sustained than is clonus. Evidence: PCS. Frequency: 8/8. (PMID:25885527;PMID:22305531;PMID:24706016;PMID:29502866;PMID:24357517)
- Pallor (HP:0000980): Abnormally pale skin. Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Cerebellar atrophy (HP:0001272): Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event. Evidence: PCS. Frequency: 1/1. (PMID:24357517)
- Cerebral cortical atrophy (HP:0002120): Atrophy of the cortex of the cerebrum. Evidence: PCS. Frequency: 2/2. (PMID:24259288;PMID:24357517)
- Cirrhosis (HP:0001394): A chronic disorder of the liver in which liver tissue becomes scarred and is partially replaced by regenerative nodules and fibrotic tissue resulting in loss of liver function. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:300868)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: PCS. Frequency: 2/2. (PMID:24259288;PMID:25885527)
- Motor delay (HP:0001270): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: PCS. Frequency: 2/2. (PMID:22305531;PMID:24357517)
- Moderately reduced visual acuity (HP:0030515): Moderate reduction of the ability to see. On the 6m visual acuity scale, moderate reduction is defined as less than 6/18 but at least 6/60. On the 20ft visual acuity scale, moderate reduction is defined as less than 20/70 but at least 20/200. On the decimal visual acuity scale, moderate reduction is defined as less than 0.3 but at least 0.1. Evidence: PCS. Frequency: 1/1. (PMID:25885527)
- Cerebral visual impairment (HP:0100704): A form of loss of vision caused by damage to the visual cortex rather than a defect in the eye. Evidence: PCS. Frequency: 3/3. (PMID:24259288)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: PCS. Frequency: 2/2. (PMID:24259288;PMID:24259184)
- 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: 1/2. (PMID:22305531)
- Redundant neck skin (HP:0005989): Excess skin around the neck, often lying in horizontal folds. Evidence: PCS. Frequency: 1/1. (PMID:25885527)
- Frontal upsweep of hair (HP:0002236): Upward and/or sideward growth of anterior hair. Evidence: PCS. Frequency: 1/1. (PMID:25885527)
- Head titubation (HP:0002599): A head tremor of moderate speed (3 to 4 Hz) in the anterior-posterior direction. Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Lateral ventricle dilatation (HP:0006956). Evidence: PCS. Frequency: 1/2. (PMID:22305531)
- Vesicoureteral reflux (HP:0000076): Abnormal (retrograde) movement of urine from the bladder into ureters or kidneys related to inadequacy of the valvular mechanism at the ureterovesicular junction or other causes. Evidence: PCS. Frequency: 4/5. (PMID:22305531;PMID:24706016)
- Status epilepticus (HP:0002133): Status epilepticus is a type of prolonged seizure resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms which lead to abnormally prolonged seizures (after time point t1). It is a condition that can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures. Evidence: PCS. Frequency: 3/3. (PMID:29502866;PMID:24357517)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: PCS. Frequency: 3/3. (PMID:24259184;PMID:29502866)
- Decreased facial expression (HP:0004673): A reduced degree of voluntary and involuntary facial movements involved in responded to others or expressing emotions. Evidence: PCS. Frequency: 1/1. (PMID:25885527)
- Febrile seizure (within the age range of 3 months to 6 years) (HP:0002373): A febrile seizure is any type of seizure (most often a generalized tonic-clonic seizure) occurring with fever (at least 38 degrees Celsius) but in the absence of central nervous system infection, severe metabolic disturbance or other alternative precipitant in children between the ages of 3 months and 6 years. Evidence: PCS. Frequency: 1/1. (PMID:24259184)
- Aplasia/Hypoplasia of the corpus callosum (HP:0007370): Absence or underdevelopment of the corpus callosum. Evidence: PCS. Frequency: 1/1. (PMID:25885527)
- Left ventricular hypertrophy (HP:0001712): Enlargement or increased size of the heart left ventricle. Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Ventricular arrhythmia (HP:0004308). Evidence: PCS. Frequency: 1/1. (PMID:25885527)
- Abnormality of the philtrum (HP:0000288): An abnormality of the philtrum. Evidence: PCS. Frequency: 1/1. (PMID:24259184)
- Moderate intellectual disability (HP:0002342): Moderate intellectual disability (ID) is defined as a type of ID characterized by moderately sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) the range of 35-49. Evidence: PCS. Frequency: 1/1. (PMID:24706016)
- Flexion contracture (HP:0001371): A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints. Evidence: PCS. Frequency: 7/7. (PMID:24259288;PMID:22305531;PMID:24706016)
- 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: 5/5. (PMID:24259288;PMID:24706016;PMID:24357517)
- Narrow mouth (HP:0000160): Distance between the commissures of the mouth more than 2 SD below the mean. Alternatively, an apparently decreased width of the oral aperture (subjective). Evidence: PCS. Frequency: 1/2. (PMID:22305531)
- 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: 3/3. (PMID:22305531;PMID:29502866)
- Coarse facial features (HP:0000280): Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues. Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Widened subarachnoid space (HP:0012704): An increase in size of the anatomic space between the arachnoid membrane and pia mater. Evidence: PCS. Frequency: 1/1. (PMID:24259184)
- Abnormal pons morphology (HP:0007361): A structural abnormality of the pons. Evidence: TAS. (OMIM:300868)
- Autism (HP:0000717): Autism is a neurodevelopmental disorder characterized by impaired social interaction and communication, and by restricted and repetitive behavior. Autism begins in childhood. It is marked by the presence of markedly abnormal or impaired development in social interaction and communication and a markedly restricted repertoire of activity and interest. Manifestations of the disorder vary greatly depending on the developmental level and chronological age of the individual (DSM-IV). Evidence: PCS. Frequency: 2/2. (PMID:24706016)
- CNS hypomyelination (HP:0003429): Reduced amount of myelin in the central nervous system resulting from defective myelinogenesis. Evidence: PCS. Frequency: 1/1. (PMID:24706016)
- Abnormal joint morphology (HP:0001367): An abnormal structure or form of the joints, i.e., one or more of the articulations where two bones join. Evidence: PCS. Frequency: 3/3. (PMID:24706016)
- Bilateral ptosis (HP:0001488). Evidence: PCS. Frequency: 1/1. (PMID:25885527)
- Skeletal muscle atrophy (HP:0003202): The presence of skeletal muscular atrophy (which is also known as amyotrophy). Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Micropenis (HP:0000054): Abnormally small penis. At birth, the normal penis is about 3 cm (stretched length from pubic tubercle to tip of penis) with micropenis less than 2.0-2.5 cm. Evidence: TAS. (OMIM:300868)
- Global developmental delay (HP:0001263): A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age. Evidence: PCS. Frequency: 16/16. (PMID:9307258;PMID:24259184;PMID:24357517)
- Focal seizure with eyelid myoclonia (HP:0011168): Focal seizure with eyelid myoclonia, not eyelid myoclonias in the context of absence seizures. Evidence: PCS. Frequency: 1/1. (PMID:29502866)
- Camptodactyly (HP:0012385): The distal interphalangeal joint and/or the proximal interphalangeal joint of the fingers or toes cannot be extended to 180 degrees by either active or passive extension. Evidence: PCS. Frequency: 1/1. (PMID:25885527)
- High anterior hairline (HP:0009890): Distance between the hairline (trichion) and the glabella (the most prominent point on the frontal bone above the root of the nose), in the midline, more than two SD above the mean. Alternatively, an apparently increased distance between the hairline and the glabella. Evidence: PCS. Frequency: 1/1. (PMID:24259184)
- Knee flexion contracture (HP:0006380): A type of knee joint contracture in which the knee is in a fixed bent (flexed) configuration such that it cannot be straightened actively or passively. Evidence: PCS. Frequency: 1/2. (PMID:22305531)
- Edema (HP:0000969): An abnormal accumulation of fluid beneath the skin, or in one or more cavities of the body. Evidence: PCS. Frequency: 1/1. (PMID:24357517)
- Spasticity (HP:0001257): A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes. Evidence: PCS. Frequency: 2/2. (PMID:24259288)
- Apnea (HP:0002104): Lack of breathing with no movement of the respiratory muscles and no exchange of air in the lungs. This term refers to a disposition to have recurrent episodes of apnea rather than to a single event. Evidence: PCS. Frequency: 3/3. (PMID:25885527;PMID:24259184;PMID:22305531)
- 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:24259288)
- Acute aspiration pneumonia (HP:0011952): An acute episode of pneumonia due to the aspiration (breathing in) of food, liquid, or gastric contents into the upper respiratory tract. Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Alveolar ridge overgrowth (HP:0009085): Increased width of the alveolar ridges. Evidence: PCS. Frequency: 2/2. (PMID:24259288;PMID:24259184)
- Reduced eye contact (HP:0000817): A reduced frequency or duration of eye contact. Evidence: PCS. Frequency: 2/2. (PMID:29502866)
- Abnormal macular morphology (HP:0001103): A structural abnormality of the macula, a region that, in a clinical context, is typically used to describe the central part of the retina within the vascular arcades. Evidence: PCS. Frequency: 1/1. (PMID:25885527)
- Macrocephaly (HP:0000256): Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium. Evidence: TAS. (OMIM:300868)
- Brisk reflexes (HP:0001348): Tendon reflexes that are noticeably more active than usual (conventionally denoted 3+ on clinical examination). Brisk reflexes may or may not indicate a neurological lesion. They are distinguished from hyperreflexia by the fact that hyerreflexia is characterized by hyperactive repeating (clonic) reflexes, which are considered to be always abnormal. Evidence: PCS. Frequency: 3/3. (PMID:24259288;PMID:22305531)
- Psoriasiform dermatitis (HP:0003765): A skin abnormality characterized by redness and irritation, with thick, red skin that displays flaky, silver-white patches (scales). Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Hyperreflexia (HP:0001347): Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles. Evidence: PCS. Frequency: 3/3. (PMID:24706016)
- Overfolded helix (HP:0000396): A condition in which the helix is folded over to a greater degree than normal. That is, excessive curling of the helix edge, whereby the free edge is parallel to the plane of the ear. Evidence: PCS. Frequency: 1/2. (PMID:22305531)
- Abnormal skin pigmentation (HP:0001000): An abnormality of the pigmentation of the skin. Evidence: TAS. (OMIM:300868)
- Abnormality of the face (HP:0000271): An abnormality of the face. Evidence: PCS. Frequency: 6/6. (PMID:24706016)
- Respiratory tract infection (HP:0011947): An infection of the upper or lower respiratory tract. Evidence: PCS. Frequency: 1/1. (PMID:24357517)
- Malar flattening (HP:0000272): Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation. Evidence: PCS. Frequency: 1/3. (PMID:22305531;PMID:24357517)
- 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: 3/3. (PMID:24706016)
- Abnormal circulating iron concentration (HP:0040130): The concentration of iron in the blood circulation is outside the limits of normal. Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Depressed nasal bridge (HP:0005280): Posterior positioning of the nasal root in relation to the overall facial profile for age. Evidence: PCS. Frequency: 3/5. (PMID:22305531;PMID:24357517;PMID:29502866)
- EEG with generalized polyspikes (HP:0012001): EEG with repetitive generalized sharp transient waves of a duration less than 80 msec. Evidence: PCS. Frequency: 2/2. (PMID:29502866)
- Testicular atrophy (HP:0000029): Wasting (atrophy) of the testicle (the male gonad) manifested by a decrease in size and potentially by a loss of fertility. Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Plagiocephaly (HP:0001357): Asymmetric head shape, which is usually a combination of unilateral occipital flattening with ipsilateral frontal prominence, leading to rhomboid cranial shape. Evidence: PCS. Frequency: 2/2. (PMID:24259288;PMID:25885527)
- Tetraplegia (HP:0002445): Paralysis of all four limbs, and trunk of the body below the level of an associated injury to the spinal cord. The etiology of quadriplegia is similar to that of paraplegia except that the lesion is in the cervical spinal cord rather than in the thoracic or lumbar segments of the spinal cord. Evidence: PCS. Frequency: 2/2. (PMID:24706016)
- Prominent occiput (HP:0000269): Increased convexity of the occiput (posterior part of the skull). Evidence: PCS. Frequency: 1/2. (PMID:22305531)
- Absent septum pellucidum (HP:0001331): Absence of the septum pellucidum (meaning translucent wall in Latin - SP), also known as the ventricle of Sylvius. The septum pellucidum is a thin, triangular double membrane separating the frontal horns of the right and left lateral ventricles of the brain. It extends between the anterior portion of the corpus callosum, and the body of the fornix and its width varies from 1.5 to 3.0 mm. Evidence: PCS. Frequency: 1/1. (PMID:22305531)
- 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: PCS. Frequency: 2/2. (PMID:29502866)
- Hearing impairment (HP:0000365): A decreased magnitude of the sensory perception of sound. Evidence: PCS. Frequency: 3/3. (PMID:24259288;PMID:25885527)
- Inability to walk (HP:0002540): Incapability to ambulate. Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Cardiac arrest (HP:0001695): An abrupt loss of heart function. Evidence: PCS. Frequency: 1/1. (PMID:24259184)
- Dystonia (HP:0001332): An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk. Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Thoracic hypoplasia (HP:0005257). Evidence: PCS. Frequency: 1/2. (PMID:22305531)
- Abnormality of the mitochondrion (HP:0012103): An anomaly of the mitochondrion, the membranous cytoplasmic organelle the interior of which is subdivided by cristae. The mitochondrion is a self replicating organelle that is the site of tissue respiration. Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- 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: 3/6. (PMID:25885527;PMID:24357517)
- Abnormal hepatic iron concentration (HP:0040134). Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Large fontanelles (HP:0000239): In newborns, the two frontal bones, two parietal bones, and one occipital bone are joined by fibrous sutures, which form a small posterior fontanelle, and a larger, diamond-shaped anterior fontanelle. These regions allow for the skull to pass the birth canal and for later growth. The fontanelles gradually ossify, whereby the posterior fontanelle usually closes by eight weeks and the anterior fontanelle by the 9th to 16th month of age. Large fontanelles are diagnosed if the fontanelles are larger than age-dependent norms. Evidence: PCS. Frequency: 1/2. (PMID:22305531)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:300868)
- Olfactory lobe agenesis (HP:0001341). Evidence: PCS. Frequency: 1/2. (PMID:22305531)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Abnormality of eye movement (HP:0000496): An abnormality in voluntary or involuntary eye movements or their control. Evidence: PCS. Frequency: 2/2. (PMID:24259288)
- Grasp reflex (HP:0030903): A type of primitive reflex that can be elicated when the hand of the examiner is gently inserted into the palm of the patient's hand. The palmar surface is stroked or simply touched. The flexor surfaces of the fingers may be stimulated also by the examiner's fingers. The stimulus should be in a distal direction. With a positive response, the patient grasps the examiner's hand with variable strength and continues to grasp as the examiner's hand is moved. Ability to release the grip voluntarily depends on the activity of the reflex; some patients can do so readily, while others can even be lifted off the bed, since the grasp has such power [NCBI Books:NBK395]. Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Bilateral fetal pyelectasis (HP:0011129): A bilateral form of fetal pyelectasis. Evidence: PCS. Frequency: 1/2. (PMID:22305531)
- Elevated hepatic iron concentration (HP:0012465): An increased level of iron in liver tissues. Evidence: TAS. (PMID:24259288)
- Abnormality of the supraorbital ridges (HP:0100538): An anomaly of the supraorbital portion of the frontal bones. Evidence: PCS. Frequency: 1/1. (PMID:25885527)
- Abnormal visual fixation (HP:0025404): Any anomaly in the process of ocular fixation, which is the maintaining of the visual gaze on a single location. Evidence: PCS. Frequency: 2/2. (PMID:29502866)
- 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:24357517)
- Birth length greater than 97th percentile (HP:0003517). Evidence: TAS. (OMIM:300868)
- Papule (HP:0200034): A circumscribed, solid elevation of skin with no visible fluid, varying in size from a pinhead to less than 10mm in diameter at the widest point. Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Brachycephaly (HP:0000248): An abnormality of skull shape characterized by a decreased anterior-posterior diameter. That is, a cephalic index greater than 81%. Alternatively, an apparently shortened anteroposterior dimension (length) of the head compared to width. Evidence: PCS. Frequency: 2/2. (PMID:24259288;PMID:25885527)
- Agenesis of permanent teeth (HP:0006349): A congenital defect characterized by the absence of one or more permanent teeth, including oligodontia, hypodontia, and adontia of the of permanent teeth. Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Hydronephrosis (HP:0000126): Severe distention of the kidney with dilation of the renal pelvis and calices. Evidence: PCS. Frequency: 1/1. (PMID:25885527)
- Myoclonus (HP:0001336): Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements. Evidence: PCS. Frequency: 3/3. (PMID:24259288;PMID:24706016;PMID:24357517)
- 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: 9/9. (PMID:25885527;PMID:24706016;PMID:24357517)
- Small nail (HP:0001792): A nail that is diminished in length and width, i.e., underdeveloped nail. Evidence: PCS. Frequency: 1/2. (PMID:22305531)
- Upslanted palpebral fissure (HP:0000582): The palpebral fissure inclination is more than two standard deviations above the mean for age (objective); or, the inclination of the palpebral fissure is greater than typical for age. Evidence: PCS. Frequency: 2/3. (PMID:24259184;PMID:22305531)
- 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: 3/4. (PMID:22305531;PMID:29502866)
- Delayed myelination (HP:0012448): Delayed myelination. Evidence: TAS. (OMIM:300868)
- Overgrowth (HP:0001548): Excessive postnatal growth which may comprise increased weight, increased length, and/or increased head circumference. Evidence: TAS. (OMIM:300868)
- Broad forehead (HP:0000337): Width of the forehead or distance between the frontotemporales is more than two standard deviations above the mean (objective); or apparently increased distance between the two sides of the forehead. Evidence: PCS. Frequency: 1/1. (PMID:25885527)
- Hydrops fetalis (HP:0001789): The abnormal accumulation of fluid in two or more fetal compartments, including ascites, pleural effusion, pericardial effusion, and skin edema. Evidence: TAS. (PMID:8599356)
- 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: 1/2. (PMID:22305531)
- 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: 1/2. (PMID:22305531)
- Gingival overgrowth (HP:0000212): Hyperplasia of the gingiva (that is, a thickening of the soft tissue overlying the alveolar ridge. The degree of thickening ranges from involvement of the interdental papillae alone to gingival overgrowth covering the entire tooth crown. Evidence: PCS. Frequency: 1/2. (PMID:22305531)
- Right ventricular hypertrophy (HP:0001667): In this case the right ventricle is more muscular than normal, causing a characteristic boot-shaped (coeur-en-sabot) appearance as seen on anterior- posterior chest x-rays. Right ventricular hypertrophy is commonly associated with any form of right ventricular outflow obstruction or pulmonary hypertension, which may in turn owe its origin to left-sided disease. The echocardiographic signs are thickening of the anterior right ventricular wall and the septum. Cavity size is usually normal, or slightly enlarged. In many cases there is associated volume overload present due to tricuspid regurgitation, in the absence of this, septal motion is normal. Evidence: PCS. Frequency: 1/1. (PMID:25885527)
- Thin bony cortex (HP:0002753): Abnormal thinning of the cortical region of bones. Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Polyhydramnios (HP:0001561): The presence of excess amniotic fluid in the uterus during pregnancy. Evidence: PCS. Frequency: 4/5. (PMID:24259184;PMID:22305531;PMID:24706016)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Thin vermilion border (HP:0000233): Height of the vermilion of the medial part of the lip more than 2 SD below the mean, or apparently reduced height of the vermilion of the lip in the frontal view. The vermilion is the red part of the lips (and confusingly, the vermilion itself is also often referred to as being equivalent the lips). Evidence: PCS. Frequency: 1/1. (PMID:24259184)
- Cerebellar hypoplasia (HP:0001321): Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time. Evidence: PCS. Frequency: 2/2. (PMID:22305531)
- Thickened nuchal skin fold (HP:0000474): A thickening of the skin thickness in the posterior aspect of the fetal neck. A nuchal fold (NF) measurement is obtained in a transverse section of the fetal head at the level of the cavum septum pellucidum and thalami, angled posteriorly to include the cerebellum. The measurement is taken from the outer edge of the occiput bone to the outer skin limit directly in the midline. An NF measurement greater than 5 mm at 14 to 17+6 weeks of gestation, or 6 mm at 18 to 28 weeks has been associated with a markedly increased risk for Down syndrome. Evidence: PCS. Frequency: 1/1. (PMID:25885527)
- Generalized tonic seizure (HP:0010818): A generalized tonic seizure is a type of generalized motor seizure characterized by bilateral limb stiffening or elevation, often with neck stiffening without a subsequent clonic phase. The tonic activity can be a sustained abnormal posture, either in extension or flexion, sometimes accompanied by tremor of the extremities. Evidence: PCS. Frequency: 2/2. (PMID:24706016)
- 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: 3/3. (PMID:24259288;PMID:25885527)
- Short neck (HP:0000470): Diminished length of the neck. Evidence: PCS. Frequency: 1/2. (PMID:22305531)
- Pneumonia (HP:0002090): Inflammation of any part of the lung parenchyma. Evidence: PCS. Frequency: 3/3. (PMID:22305531;PMID:24357517)
- Ichthyosis (HP:0008064): An abnormality of the skin characterized the presence of excessive amounts of dry surface scales on the skin resulting from an abnormality of keratinization. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:300868)
- Neuronal loss in central nervous system (HP:0002529). Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- 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: 11/11. (PMID:24259184;PMID:22305531)
- Hepatosplenomegaly (HP:0001433): Simultaneous enlargement of the liver and spleen. Evidence: PCS. Frequency: 2/2. (PMID:24259288)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: TAS. (OMIM:300868)
- Bilateral tonic-clonic seizure (HP:0002069): A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase. Evidence: PCS. Frequency: 3/3. (PMID:24357517;PMID:29502866)
- Delayed eruption of teeth (HP:0000684): Delayed tooth eruption, which can be defined as tooth eruption more than 2 SD beyond the mean eruption age. Evidence: PCS. Frequency: 2/2. (PMID:24259288)
- Elevated circulating alkaline phosphatase concentration (HP:0003155): Abnormally increased serum levels of alkaline phosphatase activity. Evidence: PCS. Frequency: 7/8. (PMID:25885527;PMID:24259184;PMID:22305531;PMID:24706016)
- 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: 4/4. (PMID:24706016)
- Hip contracture (HP:0003273): Lack of full passive range of motion (restrictions in flexion, extension, or other movements) of the hip joint resulting from structural changes of non-bony tissues, such as muscles, tendons, ligaments, joint capsules and/or skin. Evidence: PCS. Frequency: 1/2. (PMID:22305531)
- Rigidity (HP:0002063): Continuous involuntary sustained muscle contraction. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity. Evidence: PCS. Frequency: 1/1. (PMID:25885527)
- Lower limb spasticity (HP:0002061): Spasticity (velocity-dependent increase in tonic stretch reflexes with increased muscle tone and hyperexcitable tendon reflexes) in the muscles of the lower limbs, hips, and pelvis. Evidence: TAS. (OMIM:300868)
- Abdominal distention (HP:0003270): Distention of the abdomen. Evidence: PCS. Frequency: 1/1. (PMID:24259184)
- Aplasia/Hypoplasia of the cerebral white matter (HP:0012429): Absence or underdevelopment of the cerebral white matter. Evidence: PCS. Frequency: 1/1. (PMID:24259184)
- Cerebral white matter hypoplasia (HP:0012430): Underdevelopment of the cerebral white matter. Evidence: PCS. Frequency: 4/4. (PMID:24706016)
- Short finger (HP:0009381): Abnormally short finger associated with developmental hypoplasia. Evidence: PCS. Frequency: 1/1. (PMID:22305531)
- Fetal onset (HP:0011461): Onset prior to birth but after 8 weeks of embryonic development (corresponding to a gestational age of 10 weeks). Evidence: PCS. Frequency: 2/2. (PMID:22305531)
- Hypertelorism (HP:0000316): Interpupillary distance more than 2 SD above the mean (alternatively, the appearance of an increased interpupillary distance or widely spaced eyes). Evidence: PCS. Frequency: 3/3. (PMID:25885527;PMID:29502866)
- Death in infancy (HP:0001522): Death within the first 24 months of life. Evidence: PCS. Frequency: 2/2. (PMID:22305531)
- Patent ductus arteriosus (HP:0001643): In utero, the ductus arteriosus (DA) serves to divert ventricular output away from the lungs and toward the placenta by connecting the main pulmonary artery to the descending aorta. A patent ductus arteriosus (PDA) in the first 3 days of life is a physiologic shunt in healthy term and preterm newborn infants, and normally is substantially closed within about 24 hours after bith and completely closed after about three weeks. Failure of physiologcal closure is referred to a persistent or patent ductus arteriosus (PDA). Depending on the degree of left-to-right shunting, PDA can have clinical consequences. Evidence: PCS. Frequency: 1/2. (PMID:22305531)
- Anodontia (HP:0000674): The absence of all teeth from the normal series by a failure to develop. Evidence: PCS. Frequency: 1/1. (PMID:24259184)
- Round face (HP:0000311): The facial appearance is more circular than usual as viewed from the front. Evidence: PCS. Frequency: 1/1. (PMID:25885527)
- Retinal dystrophy (HP:0000556): Retinal dystrophy is an abnormality of the retina associated with a hereditary process. Retinal dystrophies are defined by their predominantly monogenic inheritance and they are frequently associated with loss or dysfunction of photoreceptor cells as a primary or secondary event. Evidence: PCS. Frequency: 1/1. (PMID:25885527)
- Generalized amyotrophy (HP:0003700): Generalized (diffuse, unlocalized) amyotrophy (muscle atrophy) affecting multiple muscles. Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Flat occiput (HP:0005469): Reduced convexity of the occiput (posterior part of skull). Evidence: PCS. Frequency: 1/1. (PMID:25885527)
- Spastic tetraplegia (HP:0002510): Spastic paralysis affecting all four limbs. Evidence: PCS. Frequency: 2/2. (PMID:24706016)
- Truncal ataxia (HP:0002078): Truncal ataxia is a sign of ataxia characterized by instability of the trunk. It usually occurs during sitting. Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Ascites (HP:0001541): Accumulation of fluid in the peritoneal cavity (between the layers of the peritoneum that lines the abdomen). Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Hypoplasia of the corpus callosum (HP:0002079): Underdevelopment of the corpus callosum. Evidence: PCS. Frequency: 9/9. (PMID:24259184;PMID:22305531;PMID:24706016)
- Generalized-onset seizure (HP:0002197): A generalized-onset seizure is a type of seizure originating at some point within, and rapidly engaging, bilaterally distributed networks. The networks may include cortical and subcortical structures but not necessarily the entire cortex. Evidence: PCS. Frequency: 1/1. (PMID:24259184)
- Microdontia (HP:0000691): Decreased size of the teeth, which can be defined as a mesiodistal tooth diameter (width) more than 2 SD below mean. Alternatively, an apparently decreased maximum width of tooth. Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Increased head circumference (HP:0040194): An abnormally increased head circumference in a growing child. Head circumference is measured with a nonelastic tape and comprises the distance from above the eyebrows and ears and around the back of the head. The measured HC is then plotted on an appropriate growth chart. Evidence: TAS. (OMIM:300868)
- Increased circulating ferritin concentration (HP:0003281): Increased concentration of ferritin in the blood circulation. Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Neuronal loss in the cerebral cortex (HP:0007190). Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- X-linked recessive inheritance (HP:0001419): A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele. Evidence: PCS. (PMID:22305531)
- Metopic synostosis (HP:0011330): Premature fusion of the metopic suture. Evidence: PCS. Frequency: 1/2. (PMID:22305531)
- Triangular mouth (HP:0000207): The presence of a triangular form of the mouth. Evidence: TAS. (OMIM:300868)
- Elbow flexion contracture (HP:0002987): An elbow contracture that limits the ability of the elbow joint to be extended (straightened), meaning that the elbow is fixed in an flexed (bent) position. Evidence: PCS. Frequency: 1/2. (PMID:22305531)
- Pierre-Robin sequence (HP:0000201): Pierre Robin malformation is a sequence of developmental malformations characterized by micrognathia (mandibular hypoplasia), glossoptosis and cleft palate. Evidence: PCS. Frequency: 1/7. (PMID:22305531;PMID:24357517)
- Abnormal cerebral white matter morphology (HP:0002500): An abnormality of the cerebral white matter. Evidence: PCS. Frequency: 1/1. (PMID:24357517)
- Microvesicular hepatic steatosis (HP:0001414): A form of hepatic steatosis characterized by the presence of small, lipid-laden vesicles in the affected hepatocytes. Evidence: PCS. Frequency: 1/2. (PMID:22305531)
- Facial asymmetry (HP:0000324): An abnormal difference between the left and right sides of the face. Evidence: PCS. Frequency: 1/1. (PMID:25885527)
- Micronodular cirrhosis (HP:0001413): A type of cirrhosis characterized by the presence of small regenerative nodules. Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Widely spaced teeth (HP:0000687): Increased spaces (diastemata) between most of the teeth in the same dental arch. Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Aspiration (HP:0002835): Inspiration of a foreign object into the airway. Evidence: PCS. Frequency: 1/1. (PMID:25885527)
- Downturned corners of mouth (HP:0002714): A morphological abnormality of the mouth in which the angle of the mouth is downturned. The oral commissures are positioned inferior to the midline labial fissure. Evidence: PCS. Frequency: 1/3. (PMID:22305531;PMID:24357517)
- Breech presentation (HP:0001623): A position of the fetus at delivery in which the fetus enters the birth canal with the buttocks or feet first. Evidence: PCS. Frequency: 2/3. (PMID:22305531;PMID:24357517)
- Splenomegaly (HP:0001744): Abnormal increased size of the spleen. Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Abnormal foot morphology (HP:0001760): An abnormality of the skeleton of foot. Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Axial hypotonia (HP:0008936): Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk. Evidence: PCS. Frequency: 5/6. (PMID:24259288;PMID:25885527;PMID:24259184;PMID:22305531;PMID:24357517)
- Opisthotonus (HP:0002179): Opisthotonus is defined as a dramatic abnormal posture due to spastic contraction of the extensor muscles of the neck, trunk, and lower extremities that produces a severe backward arching from neck to heel. In most cases, the trunk is elevated off the ground by a few inches. It is usually sudden in onset and can be sustained or repetitive. It can be considered a variant of decerebrate posturing involving a hyperextension of the neck, back, and limbs. Evidence: PCS. Frequency: 2/2. (PMID:29502866)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: PCS. Frequency: 2/2. (PMID:25885527;PMID:24259184)
- Abnormality of the glabella (HP:0002056): An abnormality of the glabella. Evidence: PCS. Frequency: 1/1. (PMID:25885527)
- Large for gestational age (HP:0001520): The term large for gestational age applies to babies whose birth weight lies above the 90th percentile for that gestational age. Evidence: PCS. Frequency: 1/1. (PMID:25885527)
- Postural tremor (HP:0002174): A type of tremors that is triggered by holding a limb in a fixed position. Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Uplifted earlobe (HP:0009909): An abnormal orientation of the earlobes such that they point out- and upward. That is, the lateral surface of ear lobe faces superiorly. Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Gliosis (HP:0002171): Gliosis is the focal proliferation of glial cells in the central nervous system. Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Optic disc pallor (HP:0000543): A pale yellow discoloration of the optic disc (the area of the optic nerve head in the retina). The optic disc normally has a pinkish hue with a central yellowish depression. Evidence: PCS. Frequency: 1/1. (PMID:25885527)
- Atrial septal defect (HP:0001631): Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum. Evidence: PCS. Frequency: 2/3. (PMID:24259184;PMID:22305531)
- Thrombocytopenia (HP:0001873): A reduction in the number of circulating thrombocytes. Evidence: PCS. Frequency: 1/1. (PMID:24259288)
- Myopia (HP:0000545): An abnormality of refraction characterized by the ability to see objects nearby clearly, while objects in the distance appear blurry. Evidence: PCS. Frequency: 1/1. (PMID:25885527)