- Decreased body weight (HP:0004325): Abnormally low body weight. Evidence: PCS. Frequency: 6/25. (PMID:33513338)
- 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: 3/25. (PMID:33513338)
- Inability to walk (HP:0002540): Incapability to ambulate. Evidence: PCS. Frequency: 4/25. (PMID:33513338)
- Short foot (HP:0001773): A measured foot length that is more than 2 SD below the mean for a newborn of 27 - 41 weeks gestation, or foot that is less than the 3rd centile for individuals from birth to 16 years of age (objective). Alternatively, a foot that appears disproportionately short (subjective). Evidence: PCS. Frequency: 2/25. (PMID:33513338)
- Recurrent lower respiratory tract infections (HP:0002783): An increased susceptibility to lower respiratory tract infections as manifested by a history of recurrent lower respiratory tract infections. Evidence: PCS. Frequency: 3/25. (PMID:33513338)
- 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: 6/10. (PMID:33513338)
- 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: 17/35. (PMID:33513338)
- 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: 2/11. (PMID:33513338)
- 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: 3/25. (PMID:33513338)
- 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: 3/25. (PMID:33513338)
- 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: 4/25. (PMID:33513338)
- Ventouse delivery (HP:0011412): Delivery of newborn by means of a ventouse, a vacuum device used to assist the delivery of a baby when the second stage of labor has not progressed adequately. Evidence: PCS. Frequency: 4/25. (PMID:33513338)
- 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: 6/25. (PMID:33513338)
- Dry skin (HP:0000958): Skin characterized by the lack of natural or normal moisture. Evidence: PCS. Frequency: 3/25. (PMID:33513338)
- Smooth philtrum (HP:0000319): Flat skin surface, with no ridge formation in the central region of the upper lip between the nasal base and upper vermilion border. Evidence: PCS. Frequency: 2/25. (PMID:33513338)
- 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: 5/25. (PMID:33513338)
- Agitation (HP:0000713): A state of excessive motor activity that is associated with mental distress or a feeling of substantial unease or inner tension. Distinguished from restlessness by the increased level of emotional distress and negative intensity of the experience. Agitation has a significant level of physical activity that is typically threatening to the self or others. Evidence: PCS. Frequency: 2/25. (PMID:33513338)
- Delayed ability to sit (HP:0025336): A failure to achieve the ability to sit at an appropriate developmental stage. Most children sit with support at 6 months of age and sit steadily without support at 9 months of age. Evidence: PCS. Frequency: 6/25. (PMID:33513338)
- Constipation (HP:0002019): Infrequent or difficult evacuation of feces. Evidence: PCS. Frequency: 6/25. (PMID:33513338)
- 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. (PMID:33513338)
- Posteriorly rotated ears (HP:0000358): A type of abnormal location of the ears in which the position of the ears is characterized by posterior rotation (the superior part of the ears is rotated towards the back of the head, and the inferior part of the ears towards the front). Evidence: PCS. Frequency: 2/25. (PMID:33513338)
- Downslanted palpebral fissures (HP:0000494): The palpebral fissure inclination is more than two standard deviations below the mean. Evidence: PCS. Frequency: 2/25. (PMID:33513338)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 4/25. (PMID:33513338)
- Recurrent urinary tract infections (HP:0000010): Repeated infections of the urinary tract. Evidence: PCS. Frequency: 2/25. (PMID:33513338)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: PCS. Frequency: 11/11. (PMID:33513338)
- 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: 8/25. (PMID:33513338)
- Thick eyebrow (HP:0000574): Increased density/number and/or increased diameter of eyebrow hairs. Evidence: PCS. Frequency: 2/25. (PMID:33513338)
- Joint hypermobility (HP:0001382): The capability that a joint (or a group of joints) has to move, passively and/or actively, beyond normal limits along physiological axes. Evidence: PCS. Frequency: 4/16. (PMID:33513338)
- 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: 5/8. (PMID:33513338)
- 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: 21/22. (PMID:33513338)
- 2-3 toe syndactyly (HP:0004691): Syndactyly with fusion of toes two and three. Evidence: PCS. Frequency: 2/25. (PMID:33513338)
- Midface retrusion (HP:0011800): Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle. Evidence: PCS. Frequency: 2/25. (PMID:33513338)
- Generalized clonic seizure (HP:0011169): Generalized clonic seizure is a type of generalized motor seizure characterized by sustained bilateral jerking, either symmetric or asymmetric, that is regularly repetitive and involves the same muscle groups. Evidence: PCS. Frequency: 2/25. (PMID:33513338)
- Maintenance insomnia (HP:0031355): Individuals affected by abnormal difficulty in staying asleep tend to wake up at night and struggle to return to sleep. This condition typically involves spending more than 30 minutes awake during the night. Evidence: PCS. Frequency: 2/25. (PMID:33513338)
- Nocturnal seizures (HP:0031951): Seizures that occur while the affected individual is sleeping. Evidence: PCS. Frequency: 2/25. (PMID:33513338)
- Drooling (HP:0002307): Habitual flow of saliva out of the mouth. Evidence: PCS. Frequency: 7/16. (PMID:33513338)
- Sandal gap (HP:0001852): A widely spaced gap between the first toe (the great toe) and the second toe. Evidence: PCS. Frequency: 2/25. (PMID:33513338)
- Focal-onset seizure (HP:0007359): A focal-onset seizure is a type of seizure originating within networks limited to one hemisphere. They may be discretely localized or more widely distributed, and may originate in subcortical structures. Evidence: PCS. Frequency: 2/25. (PMID:33513338)
- 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: 3/16. (PMID:33513338)
- Autosomal dominant inheritance (HP:0000006): 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 heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele. Evidence: PCS. (PMID:33513338)
- 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: 2/25. (PMID:33513338)
- Tremor (HP:0001337): An unintentional, oscillating to-and-fro muscle movement about a joint axis. Evidence: PCS. Frequency: 2/25. (PMID:33513338)
- Upper limb spasticity (HP:0006986). Evidence: PCS. Frequency: 2/25. (PMID:33513338)
- Myoclonus (HP:0001336): Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements. Evidence: PCS. Frequency: 2/25. (PMID:33513338)
- Widely spaced teeth (HP:0000687): Increased spaces (diastemata) between most of the teeth in the same dental arch. Evidence: PCS. Frequency: 4/25. (PMID:33513338)
- 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: 4/25. (PMID:33513338)
- 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: 2/25. (PMID:33513338)
- Generalized non-motor (absence) seizure (HP:0002121): A generalized non-motor (absence) seizure is a type of a type of dialeptic seizure that is of electrographically generalized onset. It is a generalized seizure characterized by an interruption of activities, a blank stare, and usually the person will be unresponsive when spoken to. Any ictal motor phenomena are minor in comparison to these non-motor features. Evidence: PCS. Frequency: 4/25. (PMID:33513338)
- Abnormality of prenatal development or birth (HP:0001197): An abnormality of the fetus or the birth of the fetus, excluding structural abnormalities. Evidence: PCS. Frequency: 2/15. (PMID:33513338)
- Global brain atrophy (HP:0002283): Unlocalized atrophy of the brain with decreased total brain matter volume and increased ventricular size. Evidence: PCS. Frequency: 2/25. (PMID:33513338)
- Sleep disturbance (HP:0002360): An abnormal pattern in the quality, quantity, or characteristics of sleep. Evidence: PCS. Frequency: 6/15. (PMID:33513338)
- Motor delay (HP:0001270): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: PCS. Frequency: 21/23. (PMID:33513338)
- 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: 6/25. (PMID:33513338)
- 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: 2/25. (PMID:33513338)
- Focal myoclonic seizure (HP:0011166): A type of focal motor seizure characterized by sudden, brief (<100 ms) involuntary single or multiple contraction(s) of muscles(s) or muscle groups of variable topography (axial, proximal limb, distal). Myoclonus is less regularly repetitive and less sustained than is clonus. Evidence: PCS. Frequency: 2/25. (PMID:33513338)
- Enamel hypoplasia (HP:0006297): Developmental hypoplasia of the dental enamel. Evidence: PCS. Frequency: 3/25. (PMID:33513338)
- Motor stereotypy (HP:0000733): Use of the same abnormal action in response to certain triggers or at random. They may be used as a way to regulate one's internal state but must otherwise have no apparent functional purpose. Evidence: PCS. Frequency: 7/25. (PMID:33513338)
- Short attention span (HP:0000736): Reduced attention span characterized by distractibility and impulsivity. Evidence: PCS. Frequency: 2/25. (PMID:33513338)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: PCS. Frequency: 2/25. (PMID:33513338)
- Stereotypical hand wringing (HP:0012171): Habitual clasping and wringing of the hands in the middle of the body, similar to a hand-washing movement. Evidence: PCS. Frequency: 2/25. (PMID:33513338)
- Premature birth (HP:0001622): The birth of a baby of less than 37 weeks of gestational age. Evidence: PCS. Frequency: 2/25. (PMID:33513338)
- Developmental stagnation at onset of seizures (HP:0006834): A cessation of the development of a child in the areas of motor skills, speech and language, cognitive skills, and social and/or emotional skills, following the onset of epilepsy. Evidence: PCS. Frequency: 3/25. (PMID:33513338)
- Axial hypotonia (HP:0008936): Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk. Evidence: PCS. Frequency: 3/25. (PMID:33513338)
- Oligohydramnios (HP:0001562): Diminished amniotic fluid volume in pregnancy. Evidence: PCS. Frequency: 2/25. (PMID:33513338)
- Carious teeth (HP:0000670): Caries is a multifactorial bacterial infection affecting the structure of the tooth. This term has been used to describe the presence of more than expected dental caries. Evidence: PCS. Frequency: 2/25. (PMID:33513338)
- Lateral ventricle dilatation (HP:0006956). Evidence: PCS. Frequency: 2/25. (PMID:33513338)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: PCS. Frequency: 5/15. (PMID:33513338)
- 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: 21/23. (PMID:33513338)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: PCS. Frequency: 3/25. (PMID:33513338)
- 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: 3/25. (PMID:33513338)
- 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: 4/25. (PMID:33513338)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: PCS. Frequency: 4/21. (PMID:33513338)
- 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: 6/25. (PMID:33513338)
- 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: 2/25. (PMID:33513338)
- Death in adolescence (HP:0011421): Death during adolescence, the period between childhood and adulthood (roughly between the ages of 10 and 16 years). Evidence: PCS. Frequency: 4/25. (PMID:33513338)
- Amelogenesis imperfecta (HP:0000705): A developmental dysplasia of the dental enamel. Evidence: PCS. Frequency: 4/25. (PMID:33513338)
- Abnormal dental morphology (HP:0006482): An abnormality of the morphology of the tooth. Evidence: PCS. (PMID:33513338)
- EEG with focal spike waves (HP:0011197): EEG with focal sharp transient waves of a duration less than 80 msec followed by a slow wave. Evidence: PCS. Frequency: 2/25. (PMID:33513338)
- Yellow-brown discoloration of the teeth (HP:0006286). Evidence: PCS. Frequency: 5/25. (PMID:33513338)
- Widow's peak (HP:0000349): Frontal hairline with bilateral arcs to a low point in the midline of the forehead. Evidence: PCS. Frequency: 2/25. (PMID:33513338)
- High forehead (HP:0000348): An abnormally increased height of the forehead. Evidence: PCS. Frequency: 2/25. (PMID:33513338)
- Overweight (HP:0025502): Increased body weight with a body mass index of 25-29.9 kg per square meter. Evidence: PCS. Frequency: 2/25. (PMID:33513338)
- Abnormality of vision (HP:0000504): Abnormality of eyesight (visual perception). Evidence: PCS. Frequency: 3/12. (PMID:33513338)
- Intrauterine growth retardation (HP:0001511): An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age. Evidence: PCS. Frequency: 2/25. (PMID:33513338)
- Small hand (HP:0200055): Disproportionately small hand. Evidence: PCS. Frequency: 2/25. (PMID:33513338)
- Lactose intolerance (HP:0004789): An inability to digest lactose. Evidence: PCS. Frequency: 2/25. (PMID:33513338)
- Obesity (HP:0001513): Accumulation of substantial excess body fat. Evidence: PCS. Frequency: 3/25. (PMID:33513338)
These phenotypes are associated with the disease Kohlschutter-Tonz syndrome-like (OMIM:619229).