- 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: 4/6. (PMID:33410539)
- Inappropriate crying (HP:0030215): Uncontrolled episodes of crying occur without any apparent motivating stimuli. Evidence: PCS. Frequency: 1/6. (PMID:33410539)
- Hearing impairment (HP:0000365): A decreased magnitude of the sensory perception of sound. Evidence: PCS. Frequency: 2/6. (PMID:33410539)
- Inability to walk (HP:0002540): Incapability to ambulate. Evidence: PCS. Frequency: 4/4. (PMID:30269814)
- Delayed CNS myelination (HP:0002188): Delayed myelination in the central nervous system. Evidence: PCS. Frequency: 1/6. (PMID:33410539)
- 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: 4/4. (PMID:30269814)
- 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: 6/6. Onset: Infantile onset (HP:0003593). (PMID:33410539)
- Elevated circulating alkaline phosphatase concentration (HP:0003155): Abnormally increased serum levels of alkaline phosphatase activity. Evidence: PCS. Frequency: 2/6. (PMID:33410539;PMID:30269814)
- 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: 4/4. (PMID:30269814)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: IEA. Frequency: 6/6. (PMID:33410539)
- Generalized hypotonia (HP:0001290): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: PCS. Frequency: 4/4. (PMID:30269814)
- 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: 9/10. (PMID:33410539;PMID:30269814)
- Hypoplasia of the pons (HP:0012110): Underdevelopment of the pons. Evidence: PCS. Frequency: 4/6. (PMID:33410539)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: PCS. Frequency: 3/4. (PMID:30269814)
- Vertical forehead creases (HP:0011221): Vertical soft tissue creases in the midline of the forehead, often extending from the hairline to the brow, and seen with facial expression or when the face is at rest. Evidence: PCS. Frequency: 2/4. (PMID:30269814)
- Single transverse palmar crease (HP:0000954): The distal and proximal transverse palmar creases are merged into a single transverse palmar crease. Evidence: PCS. Frequency: 1/6. (PMID:30269814)
- Macroglossia (HP:0000158): Increased length and width of the tongue. Evidence: PCS. Frequency: 4/4. (PMID:30269814)
- Constipation (HP:0002019): Infrequent or difficult evacuation of feces. Evidence: PCS. Frequency: 1/4. (PMID:30269814)
- Cystic hygroma (HP:0000476): A cystic lymphatic lesion of the neck. Evidence: PCS. Frequency: 1/4. (PMID:30269814)
- 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: 1/6. (PMID:30269814)
- Highly arched eyebrow (HP:0002553): Increased height of the central portion of the eyebrow, forming a crescent, semicircular, or inverted U shape. Evidence: PCS. Frequency: 4/4. (PMID:30269814)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 8/10. (PMID:33410539;PMID:30269814)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: PCS. Frequency: 6/6. (PMID:33410539)
- Short chin (HP:0000331): Decreased vertical distance from the vermilion border of the lower lip to the inferior-most point of the chin. Evidence: PCS. Frequency: 1/5. (PMID:30269814)
- Feeding difficulties (HP:0011968): Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it. Evidence: PCS. Frequency: 4/4. (PMID:30269814)
- 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: 2/4. (PMID:30269814)
- 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: 4/4. (PMID:30269814)
- Short digit (HP:0011927): One or more digit that appears disproportionately short compared to the hand/foot, whereby either the entire digit or a specific phalanx is shortened. Evidence: PCS. Frequency: 1/4. (PMID:30269814)
- Decreased circulating alkaline phosphatase activity (HP:0003282): Concentration or activity of alkaline phosphatase outside the upper or lower limtis of normal in the blood circulation. Evidence: PCS. Frequency: 2/4. (PMID:30269814)
- Short 4th metacarpal (HP:0010044): Short fourth metacarpal bone. Evidence: PCS. Frequency: 2/4. (PMID:30269814)
- Autistic behavior (HP:0000729): Persistent deficits in social interaction and communication and interaction as well as a markedly restricted repertoire of activity and interest as well as repetitive patterns of behavior. Evidence: PCS. Frequency: 2/6. (PMID:33410539)
- Multiple joint contractures (HP:0002828). Evidence: PCS. Frequency: 2/6. (PMID:30269814)
- Multifocal seizures (HP:0031165): Seizures that start from several different areas of the brain (i.e., with multiple ictal onset locations). Evidence: PCS. Frequency: 4/6. (PMID:33410539)
- Umbilical hernia (HP:0001537): Protrusion of abdominal contents through a defect in the abdominal wall musculature around the umbilicus. Skin and subcutaneous tissue overlie the defect. Evidence: PCS. Frequency: 1/6. (PMID:30269814)
- 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:30269814)
- Pectus carinatum (HP:0000768): A deformity of the chest caused by overgrowth of the ribs and characterized by protrusion of the sternum. Evidence: PCS. Frequency: 2/4. (PMID:30269814)
- Clinodactyly of the 5th finger (HP:0004209): Clinodactyly refers to a bending or curvature of the fifth finger in the radial direction (i.e., towards the 4th finger). Evidence: PCS. Frequency: 4/4. (PMID:30269814)
- 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: 3/6. (PMID:33410539)
- Widely spaced teeth (HP:0000687): Increased spaces (diastemata) between most of the teeth in the same dental arch. Evidence: PCS. Frequency: 1/4. (PMID:30269814)
- Short fourth metatarsal (HP:0004689): Short fourth metatarsal bone. Evidence: PCS. Frequency: 2/4. (PMID:30269814)
- Preauricular skin tag (HP:0000384): A rudimentary tag of skin often containing ear tissue including a core of cartilage and located just anterior to the auricle (outer part of the ear). Evidence: PCS. Frequency: 1/4. (PMID:30269814)
- Deep philtrum (HP:0002002): Accentuated, prominent philtral ridges giving rise to an exaggerated groove in the midline between the nasal base and upper vermillion border. Evidence: PCS. Frequency: 2/4. (PMID:30269814)
- Inguinal hernia (HP:0000023): Protrusion of the contents of the abdominal cavity through the inguinal canal. Evidence: PCS. Frequency: 1/4. (PMID:30269814)
- Brachydactyly (HP:0001156): Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here. Evidence: PCS. Frequency: 3/4. (PMID:30269814)
- 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: 2/4. (PMID:30269814)
- Cerebral cortical atrophy (HP:0002120): Atrophy of the cortex of the cerebrum. Evidence: PCS. Frequency: 2/4. (PMID:30269814)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: PCS. Frequency: 2/4. (PMID:30269814)
- 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: 3/4. (PMID:30269814)
- Short distal phalanx of finger (HP:0009882): Short distance from the end of the finger to the most distal interphalangeal crease or the distal interphalangeal joint flexion point. That is, hypoplasia of one or more of the distal phalanx of finger. Evidence: PCS. Frequency: 1/6. (PMID:30269814)
- Fetal akinesia sequence (HP:0001989): Decreased fetal activity associated with multiple joint contractures, facial anomalies and pulmonary hypoplasia. Ultrasound examination may reveal polyhydramnios, ankylosis, scalp edema, and decreased chest movements (reflecting pulmonary hypoplasia). Evidence: PCS. Frequency: 2/6. (PMID:30269814)
- 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: 3/4. (PMID:30269814)
- Cerebellar vermis atrophy (HP:0006855): Wasting (atrophy) of the vermis of cerebellum. Evidence: PCS. Frequency: 2/6. (PMID:33410539)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: PCS. Frequency: 6/6. (PMID:33410539)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: PCS. Frequency: 1/4. (PMID:30269814)
- Long nose (HP:0003189): Distance from nasion to subnasale more than two standard deviations above the mean, or alternatively, an apparently increased length from the nasal root to the nasal base. Evidence: PCS. Frequency: 1/6. (PMID:30269814)
- 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: 5/6. (PMID:33410539)
- Cardiomegaly (HP:0001640): Increased size of the heart, clinically defined as an increased transverse diameter of the cardiac silhouette that is greater than or equal to 50% of the transverse diameter of the chest (increased cardiothoracic ratio) on a posterior-anterior projection of a chest radiograph or a computed tomography. Evidence: PCS. Frequency: 1/4. (PMID:30269814)
- Gait disturbance (HP:0001288): The term gait disturbance can refer to any disruption of the ability to walk. Evidence: PCS. Frequency: 4/4. (PMID:30269814)
- Thickened helices (HP:0000391): Increased thickness of the helix of the ear. Evidence: PCS. Frequency: 4/4. (PMID:30269814)
- 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: 6/6. (PMID:33410539)
- Severe global developmental delay (HP:0011344): A severe delay in the achievement of motor or mental milestones in the domains of development of a child. Evidence: PCS. Frequency: 6/6. (PMID:33410539)
- 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: 1/6. (PMID:33410539)
- Arthrogryposis multiplex congenita (HP:0002804): Multiple congenital contractures in different body areas. Evidence: PCS. Frequency: 2/6. Onset: Fetal onset (HP:0011461). (PMID:30269814)
- 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: 3/6. (PMID:33410539)
- 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: 1/4. (PMID:30269814)
These phenotypes are associated with the disease glycosylphosphatidylinositol biosynthesis defect 18 (OMIM:618143).