Phenotypes associated with the disease cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy 1 (OMIM:621295):
- Astigmatism (HP:0000483): A type of refraction error associated with abnormal curvatures on the anterior and/or posterior surface of the cornea. Evidence: PCS. Frequency: 1/11. (PMID:39191170)
- Hemiplegia (HP:0002301): Paralysis (complete loss of muscle function) in the arm, leg, and in some cases the face on one side of the body. Evidence: PCS. Frequency: 3/3. (PMID:35026854;PMID:39191170)
- Stroke (HP:0001297): Sudden impairment of blood flow to a part of the brain due to occlusion or rupture of an artery to the brain. Evidence: PCS. Frequency: 3/4. (PMID:35026854;PMID:39191170;PMID:32980981)
- 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: 3/13. (PMID:37688971;PMID:25870235;PMID:39191170)
- Prominent fingertip pads (HP:0001212): A soft tissue prominence of the ventral aspects of the fingertips. The term "persistent fetal fingertip pads" is often used as a synonym, but should better not be used because it implies knowledge of history of the patient which often does not exist. Evidence: PCS. Frequency: 1/16. (PMID:39191170)
- 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:38824264)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 14/26. (PMID:37688971;PMID:38824264;PMID:35026854;PMID:39191170;PMID:32980981)
- 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: 1/16. (PMID:39191170)
- Aphasia (HP:0002381): An acquired language impairment of some or all of the abilities to produce or comprehend speech and to read or write. Evidence: PCS. Frequency: 1/1. (PMID:25870235)
- Caesarean section (HP:0011410): Delivery of a fetus through surgical incisions made through the abdominal wall (laparotomy) and the uterine wall (hysterotomy). Evidence: PCS. Frequency: 1/1. (PMID:35026854)
- Epiretinal membrane (HP:0100014): An epiretinal membrane is a thin sheet of fibrous tissue on the surface of the retina along the inner limiting membrane. It appears as a greyish semi-translucent avascular membrane over the internal limiting membrane (ILM) on the surface of the retina. Evidence: PCS. Frequency: 1/11. (PMID:39191170)
- 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: 3/3. (PMID:37688971;PMID:25870235;PMID:35026854)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: PCS. Frequency: 1/1. (PMID:37688971)
- Sepsis (HP:0100806): Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Evidence: PCS. Frequency: 1/1. (PMID:37688971)
- 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: 1/16. (PMID:39191170)
- Unilateral ptosis (HP:0007687): A unilateral form of ptosis. Evidence: PCS. Frequency: 2/11. (PMID:39191170)
- Leukodystrophy (HP:0002415): Leukodystrophy refers to deterioration of white matter of the brain resulting from degeneration of myelin sheaths in the CNS. Their basic defect is directly related to the synthesis and maintenance of myelin membranes. Symmetric white matter involvement at MRI is a typical finding in patients with leukodystrophies. Evidence: PCS. Frequency: 2/2. (PMID:37688971)
- Cystic hygroma (HP:0000476): A cystic lymphatic lesion of the neck. Evidence: PCS. Frequency: 1/12. (PMID:39191170)
- Laryngomalacia (HP:0001601): Laryngomalacia is a congenital abnormality of the laryngeal cartilage in which the cartilage is floppy and prolapses over the larynx during inspiration. Evidence: PCS. Frequency: 1/11. (PMID:39191170)
- Nausea and vomiting (HP:0002017): Nausea is a commonly encountered symptom that has been defined as an unpleasant painless subjective feeling that one will imminently vomit. Vomiting has been defined as the forceful expulsion of the contents of the stomach, duodenum, or jejunum through the oral cavity. While nausea and vomiting are often thought to exist on a temporal continuum, this is not always the case. There are situations when severe nausea may be present without emesis and less frequently, when emesis may be present without preceding nausea. Evidence: PCS. Frequency: 1/1. (PMID:35026854)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 5/14. (PMID:35026854;PMID:39191170)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: PCS. Frequency: 2/17. (PMID:39191170)
- 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:35026854)
- Lower limb hyperreflexia (HP:0002395): Increased intensity of the a reflex in the leg. Evidence: PCS. Frequency: 2/2. (PMID:39191170)
- Poor suck (HP:0002033): An inadequate sucking reflex, resulting in the difficult of newborns to be breast-fed. Evidence: PCS. Frequency: 2/11. (PMID:39191170)
- 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: 1/17. (PMID:39191170)
- 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:25870235)
- Long eyelashes (HP:0000527): Mid upper eyelash length >10 mm or increased length of the eyelashes (subjective). Evidence: PCS. Frequency: 1/16. (PMID:39191170)
- Auditory hallucination (HP:0008765): Perception of sounds without auditory stimulus. Evidence: PCS. Frequency: 1/1. (PMID:39191170)
- Drooling (HP:0002307): Habitual flow of saliva out of the mouth. Evidence: PCS. Frequency: 1/1. (PMID:37688971)
- Retinopathy (HP:0000488): Any noninflammatory disease of the retina. This nonspecific term is retained here because of its wide use in the literature, but if possible new annotations should indicate the precise type of retinal abnormality. Evidence: PCS. Frequency: 2/2. (PMID:37688971)
- Thoracic scoliosis (HP:0002943). Evidence: PCS. Frequency: 1/1. (PMID:39191170)
- 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: 1/16. (PMID:39191170)
- Subependymal nodules (HP:0009716): Small nodular masses which originate in the subependymal region of the lateral ventricles and protrude into the ventricular cavity. They may represent subependymal hamartomas of tuberous sclerosis. Evidence: PCS. Frequency: 4/4. (PMID:39191170)
- Visual hallucination (HP:0002367): Visual perception in the absence of a visual stimulus. Evidence: PCS. Frequency: 1/1. (PMID:39191170)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 1/18. (PMID:39191170)
- Long philtrum (HP:0000343): Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border. Evidence: PCS. Frequency: 3/16. (PMID:39191170)
- Retinal cotton wool spot (HP:0031606): Fluffy white patch in the inner retina, representing localized areas of dense white swelling of the retinal nerve fiber layer. Evidence: PCS. Frequency: 1/11. (PMID:39191170)
- 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:35026854)
- Moderate hypermetropia (HP:0031729): A form of hypermetropia with more than +2.00 diopters but not more than +5.00 diopters. Evidence: PCS. Frequency: 1/1. (PMID:37688971)
- Motor delay (HP:0001270): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: PCS. Frequency: 3/5. (PMID:39191170)
- Brain atrophy (HP:0012444): Partial or complete wasting (loss) of brain tissue that was once present. Evidence: PCS. Frequency: 1/1. (PMID:37688971)
- Livedo reticularis (HP:0033505): Livedo reticularis is characterized by the presence of a bluish purple, mottled or netlike pattern in unbroken circles on the skin. Exposure to cold environments usually intensifies the vascular pattern. Presumably, the condition results from slow or stagnant blood flow, vessel-wall pathology, and decreased oxygen tension. Evidence: PCS. Frequency: 4/21. (PMID:25870235;PMID:35026854;PMID:39191170;PMID:32980981)
- Cognitive impairment (HP:0100543): Abnormal cognition is characterized by deficits in thinking, reasoning, or remembering. Evidence: PCS. Frequency: 2/2. (PMID:32980981)
- 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:39191170)
- Anterior synechiae of the anterior chamber (HP:0011483): Adhesions between the iris and the cornea. Evidence: PCS. Frequency: 1/11. (PMID:39191170)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: PCS. Frequency: 0/1. (PMID:35026854)
- Fever (HP:0001945): Body temperature elevated above the normal range. Evidence: PCS. Frequency: 1/1. (PMID:35026854)
- Hemiparesis (HP:0001269): Loss of strength in the arm, leg, and sometimes face on one side of the body. Hemiplegia refers to a complete loss of strength, whereas hemiparesis refers to an incomplete loss of strength. Evidence: PCS. Frequency: 3/13. (PMID:39191170;PMID:32980981)
- Nocturnal hypoventilation (HP:0002877): An abnormal reduction in alveolar ventilation occurring during sleep. This is characterized by a rise in arterial carbon dioxide. Evidence: PCS. Frequency: 1/1. (PMID:25870235)
- Cerebral calcification (HP:0002514): The presence of calcium deposition within the cerebrum. Evidence: PCS. Frequency: 0/1. (PMID:35026854)
- Prolonged neonatal jaundice (HP:0006579): Neonatal jaundice refers to a yellowing of the skin and other tissues of a newborn infant as a result of increased concentrations of bilirubin in the blood. Neonatal jaundice affects over half of all newborns to some extent in the first week of life. Prolonged neonatal jaundice is said to be present if the jaundice persists for longer than 14 days in term infants and 21 days in preterm infants. Evidence: PCS. Frequency: 4/12. (PMID:37688971;PMID:39191170)
- Meningitis (HP:0001287): Inflammation of the meninges. Evidence: PCS. Frequency: 1/1. (PMID:37688971)
- Oligohydramnios (HP:0001562): Diminished amniotic fluid volume in pregnancy. Evidence: PCS. Frequency: 5/14. (PMID:37688971;PMID:35026854;PMID:39191170)
- Cerebellar vermis hypoplasia (HP:0001320): Underdevelopment of the vermis of cerebellum. Evidence: PCS. Frequency: 1/1. (PMID:35026854)
- Polyhydramnios (HP:0001561): The presence of excess amniotic fluid in the uterus during pregnancy. Evidence: PCS. Frequency: 1/1. (PMID:37688971)
- Lateral ventricle dilatation (HP:0006956). Evidence: PCS. Frequency: 3/3. (PMID:25870235;PMID:35026854)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: PCS. Frequency: 3/3. (PMID:25870235;PMID:32980981)
- Juvenile onset (HP:0003621): Onset of signs or symptoms of disease between the age of 5 and 15 years. Evidence: PCS. Frequency: 2/3. (PMID:25870235;PMID:32980981)
- 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: 2/2. (PMID:39191170)
- 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: 1/1. (PMID:35026854)
- Spastic tetraparesis (HP:0001285): Spastic weakness affecting all four limbs. Evidence: PCS. Frequency: 2/2. (PMID:39191170)
- Raynaud phenomenon (HP:0030880). Evidence: PCS. Frequency: 1/15. (PMID:39191170)
- Abnormal dentate nucleus morphology (HP:0100321): An abnormality of the dentate nucleus. Evidence: PCS. Frequency: 1/1. (PMID:38824264)
- Placenta previa (HP:0430070): Implantation of the placenta over or near the internal os of the cervix. Evidence: PCS. Frequency: 1/12. (PMID:39191170)
- Reduced cerebral white matter volume (HP:0034295): An abnormally low volume of the white matter of the brain. Evidence: PCS. Frequency: 3/3. (PMID:35026854)
- Inappropriate laughter (HP:0000748): Laughing that may be excessive and/or inappropriate in context (e.g., laughing at a funeral while others are crying). Evidence: PCS. Frequency: 1/1. (PMID:32980981)
- Abnormal pyramidal sign (HP:0007256): Functional neurological abnormalities related to dysfunction of the pyramidal tract. Evidence: PCS. Frequency: 1/1. (PMID:25870235)
- Decreased fetal movement (HP:0001558): An abnormal reduction in quantity or strength of fetal movements. Evidence: PCS. Frequency: 1/1. (PMID:35026854)
- Visual impairment (HP:0000505): Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery. Evidence: PCS. Frequency: 3/19. (PMID:37688971;PMID:39191170)
- Antiphospholipid antibody positivity (HP:0003613): The presence of circulating autoantibodies to phospholipids. Evidence: PCS. Frequency: 0/1. (PMID:32980981)
- Attention deficit hyperactivity disorder (HP:0007018): Attention deficit hyperactivity disorder (ADHD) manifests at age 2-3 years or by first grade at the latest. The main symptoms are distractibility, impulsivity, hyperactivity, and often trouble organizing tasks and projects, difficulty going to sleep, and social problems from being aggressive, loud, or impatient. Evidence: PCS. Frequency: 1/1. (PMID:39191170)
- Syncope (HP:0001279): A transient loss of consciousness (i.e., characterized by a rapid onset, a short duration, and a spontaneous and complete recovery) due to cerebral hypoperfusion. Evidence: PCS. Frequency: 1/1. (PMID:32980981)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: PCS. Frequency: 1/16. (PMID:39191170)
- 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: 2/4. (PMID:39191170)
- Mild intellectual disability (HP:0001256): Mild intellectual disability (ID) is defined as a type of ID characterized by mildly sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) the range of 50-69. Evidence: PCS. Frequency: 3/3. (PMID:39191170)
- 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: 7/20. (PMID:37688971;PMID:38824264;PMID:25870235;PMID:35026854;PMID:39191170)
- Gait ataxia (HP:0002066): A type of ataxia characterized by the impairment of the ability to coordinate the movements required for normal walking. Gait ataxia is characteirzed by a wide-based staggering gait with a tendency to fall. Evidence: PCS. Frequency: 1/1. (PMID:39191170)
- Deep cerebral white matter hyperintensities (HP:0030892): Areas of brighter than expected signal on magnetic resonance imaging emanating from locations distant from the ventricular system. Evidence: PCS. Frequency: 2/2. (PMID:37688971;PMID:38824264)
- 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: 8/18. (PMID:25870235;PMID:35026854;PMID:39191170)
- Periventricular white matter hyperintensities (HP:0030891): Areas of brighter than expected signal on magnetic resonance imaging emanating from the cerebral white matter that surrounds the cerebral ventricles. Evidence: PCS. Frequency: 3/3. (PMID:38824264;PMID:32980981)
- 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: PCS. Frequency: 7/15. (PMID:39191170;PMID:32980981)
- 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: PCS. Frequency: 1/1. (PMID:39191170)
- 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: 2/16. (PMID:39191170)
- Interictal epileptiform activity (HP:0011182): Epileptiform activity refers to distinctive EEG waves or complexes distinguished from background activity found in in a proportion of human subjects with epilepsy, but which can also be found in subjects without seizures. Interictal epileptiform activity refers to such activity that occurs in the absence of a clinical or subclinical seizure. Evidence: PCS. Frequency: 0/1. (PMID:38824264)
- Mild global developmental delay (HP:0011342): A mild delay in the achievement of motor or mental milestones in the domains of development of a child. Evidence: PCS. Frequency: 2/2. (PMID:39191170)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 9/18. (PMID:39191170)
- Young adult onset (HP:0011462): Onset of disease at the age of between 16 and 40 years. Evidence: PCS. Frequency: 1/18. (PMID:39191170)
- Varicose veins (HP:0002619): Enlarged and tortuous veins. Evidence: PCS. Frequency: 2/2. (PMID:38824264;PMID:39191170)
- Anger (HP:0031473): A state of excessive negative emotional reactivity characterized by strong feelings of hostility or antagonism typically in response to perceived provocation. It is often accompanied by physiological arousal (e.g., increased heart rate, muscle tension, or activation of the sympathetic nervous system) and expressions of blame, perceived injustice, or judgment. The experience of anger may be directed outwardly toward individuals, groups, objects, or abstract entities, or inwardly toward oneself. Evidence: PCS. Frequency: 1/1. (PMID:35026854)
- 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: 2/16. (PMID:39191170)
- Esodeviation (HP:0020045): A manifest or latent ocular deviation in which one or both eyes tends to deviate nasally. Evidence: PCS. Frequency: 1/1. (PMID:37688971)
- Dental crowding (HP:0000678): Changes in alignment of teeth in the dental arch. Evidence: PCS. Frequency: 0/16. (PMID:39191170)
- Hyperpigmentation of the skin (HP:0000953): A darkening of the skin related to an increase in melanin production and deposition. Evidence: PCS. Frequency: 1/15. (PMID:39191170)
- Vascular dilatation (HP:0002617): An abnormal increase in the diameter of an artery or vein, either as a diffuse dilatation or as a localized, sac-like outpouching of the vessel wall (aneurysm). Evidence: PCS. Frequency: 1/1. (PMID:25870235)
- 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: 1/1. (PMID:37688971)
- Posterior vitreous detachment (HP:0001489): Separation of the vitreous humor from the retina. Evidence: PCS. Frequency: 1/11. (PMID:39191170)
- Round face (HP:0000311): The facial appearance is more circular than usual as viewed from the front. Evidence: PCS. Frequency: 1/16. (PMID:39191170)
- Bilateral ptosis (HP:0001488). Evidence: PCS. Frequency: 2/11. (PMID:39191170)
- Cavitation of the basal ganglia (HP:0007007): The formation of small cavities in the tissue of the basal ganglia. Evidence: PCS. Frequency: 1/1. (PMID:25870235)
- 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: PCS. Frequency: 12/17. (PMID:35026854;PMID:39191170)
- Thick eyebrow (HP:0000574): Increased density/number and/or increased diameter of eyebrow hairs. Evidence: PCS. Frequency: 1/16. (PMID:39191170)
- EEG abnormality (HP:0002353): Abnormality observed by electroencephalogram (EEG), which is used to record of the brain's spontaneous electrical activity from multiple electrodes placed on the scalp. Evidence: PCS. Frequency: 4/10. (PMID:39191170)
- Migraine (HP:0002076): Migraine is a chronic neurological disorder characterized by episodic attacks of headache and associated symptoms. Evidence: PCS. Frequency: 2/2. (PMID:35026854;PMID:32980981)
- Dysarthria (HP:0001260): Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed. Evidence: PCS. Frequency: 4/13. (PMID:39191170;PMID:32980981)
- 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: 15/17. (PMID:37688971;PMID:35026854;PMID:39191170)
- Fatigue (HP:0012378): A subjective feeling of tiredness characterized by a lack of energy and motivation. Evidence: PCS. Frequency: 1/1. (PMID:38824264)
- Livedo racemosa (HP:0033260): Livedo racemosa describes a reddish-blue mottling of the skin in an irregular, reticular pattern. It differs from the more common livedo reticularis by its shape. Livedo racemosa consists of broken circular segments resulting in a seemingly larger pattern, as opposed to the fine, regular, complete network of livedo reticularis. Livedo racemosa results from permanent impairment of peripheral blood flow and, unlike livedo reticularis, it persists on warming. Evidence: PCS. Frequency: 1/1. (PMID:38824264)
- Simple febrile seizure (HP:0011171): A short generalized seizure, of a duration of <15 min, not recurring within 24 h, occurring during a febrile episode not caused by an acute disease of the nervous system intracranial infection or severe metabolic disturbance. Evidence: PCS. Frequency: 2/2. (PMID:39191170)
- Appendicular spasticity (HP:0034353): A type of spasticity that affects one or more limbs (arms or legs). Evidence: PCS. Frequency: 2/2. (PMID:37688971;PMID:39191170)
- Upper limb hyperreflexia (HP:0007350): Increased intensity of the a reflex in the arm. Evidence: PCS. Frequency: 1/1. (PMID:39191170)
- Primary microcephaly (HP:0011451): Head circumference below 2 standard deviations below the mean for age and gender at birth. Evidence: PCS. Frequency: 1/1. (PMID:35026854)
- Limb hypertonia (HP:0002509). Evidence: PCS. Frequency: 1/1. (PMID:37688971)
- 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: 10/16. (PMID:35026854;PMID:39191170)
- Bilateral cryptorchidism (HP:0008689): Absence of 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: 1/2. (PMID:39191170)
- Optic neuropathy (HP:0001138). Evidence: PCS. Frequency: 1/1. (PMID:37688971)
- Abnormal diffusion weighted cerebral MRI morphology (HP:0032615): A diffusion abnormality observed in diffusion-weighted magnetic resonance imaging (MRI) of the brain. Molecular diffusion refers to the notion that any type of molecule in a fluid (eg, water) is randomly displaced as the molecule is agitated by thermal energy. Restricted diffusion of water appears bright on diffusion-weighted images. Evidence: PCS. Frequency: 2/2. (PMID:35026854)
- Clonus (HP:0002169): A series of rhythmic and involuntary muscle contractions (at a frequency of about 5 to 7 Hz) that occur in response to an abruptly applied and sustained stretch. Evidence: PCS. Frequency: 1/2. (PMID:37688971)
- Vertigo (HP:0002321): An abnormal sensation of spinning while the body is actually stationary. Evidence: PCS. Frequency: 2/2. (PMID:38824264;PMID:32980981)
- Hypermetropia (HP:0000540): An abnormality of refraction characterized by the ability to see objects in the distance clearly, while objects nearby appear blurry. Evidence: PCS. Frequency: 1/11. (PMID:39191170)
- Pseudobulbar signs (HP:0002200): Pseudobulbar signs result from injury to an upper motor neuron lesion to the corticobulbar pathways in the pyramidal tract. Patients have difficulty chewing, swallowing and demonstrate slurred speech (often initial presentation) as well as abnormal behavioral symptoms such as inappropriate emotional outbursts of uncontrolled laughter or weeping etc. Evidence: PCS. Frequency: 1/1. (PMID:32980981)
- Urinary incontinence (HP:0000020): Loss of the ability to control the urinary bladder leading to involuntary urination. Evidence: PCS. Frequency: 2/2. (PMID:38824264;PMID:32980981)
- Anisometropia (HP:0012803): Inequality of refractive power of the two eyes. Evidence: PCS. Frequency: 1/11. (PMID:39191170)
- Frequent temper tantrums (HP:0025161): Temper tantrums that occur more frequently compared to the temper tantrums that are a part of the normal developmental process. Evidence: PCS. Frequency: 1/1. (PMID:35026854)
- Abnormal circulating creatine kinase activity (HP:0040081): Any deviation from the normal activity of creatine kinase in the blood circulation. Evidence: PCS. Frequency: 4/4. (PMID:39191170)
- 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: 1/1. (PMID:35026854)
- Focal T2 hyperintense basal ganglia lesion (HP:0007183): A lighter than expected T2 signal on magnetic resonance imaging (MRI) of the basal ganglia. This term refers to a localized hyperintensity affecting a particular region of the basal ganglia. Evidence: PCS. Frequency: 1/1. (PMID:25870235)
- Ventricular septal defect (HP:0001629): A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum. Evidence: PCS. Frequency: 2/2. (PMID:37688971)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 1/1. (PMID:38824264)
- Oculomotor apraxia (HP:0000657): Ocular motor apraxia is a deficiency in voluntary, horizontal, lateral, fast eye movements (saccades) with retention of slow pursuit movements. The inability to follow objects visually is often compensated by head movements. There may be decreased smooth pursuit, and cancelation of the vestibulo-ocular reflex. Evidence: PCS. Frequency: 1/1. (PMID:37688971)
- Facial diplegia (HP:0001349): Facial diplegia refers to bilateral facial palsy (bilateral facial palsy is much rarer than unilateral facial palsy). Evidence: PCS. Frequency: 3/18. (PMID:37688971;PMID:39191170)
- 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: 1/16. (PMID:39191170)
- Headache (HP:0002315): Cephalgia, or pain sensed in various parts of the head, not confined to the area of distribution of any nerve. Evidence: PCS. Frequency: 5/16. (PMID:39191170)
- 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: PCS. Frequency: 1/16. (PMID:39191170)
- 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:37688971;PMID:39191170)
- Congenital diaphragmatic hernia (HP:0000776): The presence of a hernia of the diaphragm present at birth. Evidence: PCS. Frequency: 1/11. (PMID:39191170)
- Hyperreflexia (HP:0001347): Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles. Evidence: PCS. Frequency: 14/15. (PMID:25870235;PMID:39191170)
- Axial hypotonia (HP:0008936): Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk. Evidence: PCS. Frequency: 2/2. (PMID:37688971)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: PCS. Frequency: 1/1. (PMID:35026854)
- 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: 1/2. (PMID:35026854)
- Narrow palpebral fissure (HP:0045025): Reduction in the vertical distance between the upper and lower eyelids. Evidence: PCS. Frequency: 1/16. (PMID:39191170)
- Gliosis (HP:0002171): Gliosis is the focal proliferation of glial cells in the central nervous system. Evidence: PCS. Frequency: 1/1. (PMID:25870235)
- Postural instability (HP:0002172): A tendency to fall or the inability to keep oneself from falling; imbalance. The retropulsion test is widely regarded as the gold standard to evaluate postural instability, Use of the retropulsion test includes a rapid balance perturbation in the backward direction, and the number of balance correcting steps (or total absence thereof) is used to rate the degree of postural instability. Healthy subjects correct such perturbations with either one or two large steps, or without taking any steps, hinging rapidly at the hips while swinging the arms forward as a counterweight. In patients with balance impairment, balance correcting steps are often too small, forcing patients to take more than two steps. Taking three or more steps is generally considered to be abnormal, and taking more than five steps is regarded as being clearly abnormal. Markedly affected patients continue to step backward without ever regaining their balance and must be caught by the examiner (this would be called true retropulsion). Even more severely affected patients fail to correct entirely, and fall backward like a pushed toy soldier, without taking any corrective steps. Evidence: PCS. Frequency: 1/1. (PMID:38824264)
- Depressed nasal bridge (HP:0005280): Posterior positioning of the nasal root in relation to the overall facial profile for age. Evidence: PCS. Frequency: 2/16. (PMID:39191170)
- Small for gestational age (HP:0001518): Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age. Evidence: PCS. Frequency: 3/3. (PMID:35026854)
- Palmar hyperhidrosis (HP:0006089). Evidence: PCS. Frequency: 1/1. (PMID:38824264)
- Hypothyroidism (HP:0000821): Deficiency of thyroid hormone. Evidence: PCS. Frequency: 2/2. (PMID:38824264;PMID:35026854)
- Abnormal nerve conduction velocity (HP:0040129). Evidence: PCS. Frequency: 0/1. (PMID:37688971)
- Intrauterine growth retardation (HP:0001511): An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age. Evidence: PCS. Frequency: 3/12. (PMID:39191170)
- Synophrys (HP:0000664): Meeting of the medial eyebrows in the midline. Evidence: PCS. Frequency: 9/16. (PMID:39191170)
- Transient ischemic attack (HP:0002326). Evidence: PCS. Frequency: 3/19. (PMID:35026854;PMID:39191170)
- Dolichocephaly (HP:0000268): An abnormality of skull shape characterized by a increased anterior-posterior diameter, i.e., an increased antero-posterior dimension of the skull. Cephalic index less than 76%. Alternatively, an apparently increased antero-posterior length of the head compared to width. Often due to premature closure of the sagittal suture. Evidence: PCS. Frequency: 1/16. (PMID:39191170)
- Vascular granular osmiophilic material deposition (HP:0003657): Accumulation of granular osmiophilic material in blood vessel walls. Osmiophilic material becomes black upon staining with osmium tetroxide. Deposition of granular osmiophilic material (GOM) is the vascular pathological hallmark of CADASIL, which is the most prevalent hereditary small vessel disease and is caused by missense mutations in the NOTCH3 gene. GOM have been shown to contain NOTCH3 ectodomain (NOTCH3ECD) and extracellular matrix proteins, and can be visualized ultrastructurally in the tunica media of small arteries and capillaries. These electron dense GOM deposits are located in the basement membrane of mural cells, i.e. vascular smooth muscle cells and pericytes. In both manifest and pre-manifest CADASIL patients, GOM deposits are present not only in brain vessels, but also in vessels of other organs, such as the skin. Evidence: PCS. Frequency: 0/2. (PMID:25870235;PMID:39191170)
- 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: 1/10. (PMID:39191170)
- Obesity (HP:0001513): Accumulation of substantial excess body fat. Evidence: PCS. Frequency: 1/1. (PMID:39191170)
- Horizontal nystagmus (HP:0000666): Nystagmus consisting of horizontal to-and-fro eye movements. Evidence: PCS. Frequency: 1/1. (PMID:32980981)