- Recurrent aspiration pneumonia (HP:0002100): Increased susceptibility to aspiration pneumonia, defined as pneumonia due to breathing in foreign material, as manifested by a medical history of repeated episodes of aspiration pneumonia. Evidence: PCS. Frequency: 1/2. (PMID:33833240)
- 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: 7/7. (PMID:33833240;PMID:34909687)
- 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: 1/2. (PMID:33833240)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 1/2. (PMID:33833240)
- 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: 1/2. (PMID:33833240)
- 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: 5/5. (PMID:34909687)
- Osteoporosis (HP:0000939): Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD). Evidence: PCS. Frequency: 1/2. (PMID:33833240)
- Young adult onset (HP:0011462): Onset of disease at the age of between 16 and 40 years. Evidence: PCS. Frequency: 1/5. (PMID:34909687)
- Cortical dysplasia (HP:0002539): The presence of developmental dysplasia of the cerebral cortex. Evidence: PCS. Frequency: 1/2. (PMID:33833240)
- Atrophy/Degeneration affecting the brainstem (HP:0007366). Evidence: PCS. Frequency: 1/2. (PMID:33833240)
- 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: 5/5. (PMID:34909687)
- Neonatal onset (HP:0003623): Onset of signs or symptoms of disease within the first 28 days of life. Evidence: PCS. Frequency: 1/2. (PMID:33833240)
- Spastic tetraplegia (HP:0002510): Spastic paralysis affecting all four limbs. Evidence: PCS. Frequency: 1/2. (PMID:33833240)
- Polyhydramnios (HP:0001561): The presence of excess amniotic fluid in the uterus during pregnancy. Evidence: PCS. Frequency: 1/2. (PMID:33833240)
- Juvenile onset (HP:0003621): Onset of signs or symptoms of disease between the age of 5 and 15 years. Evidence: PCS. Frequency: 4/5. (PMID:34909687)
- Intermittent diarrhea (HP:0002254): Repeated episodes of diarrhea separated by periods without diarrhea. Evidence: PCS. Frequency: 1/2. (PMID:33833240)
- 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: 1/2. (PMID:33833240)
- Feeding difficulties (HP:0011968): Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it. Evidence: PCS. Frequency: 1/2. (PMID:33833240)
- Erratic myoclonus (HP:0025357): A type of myoclonus in which the myoclonias shift from body region to another in a random and asynchronous fashion. Erratic myoclonus can affect the face or limbs, are brief, single or repetitive, very frequent and nearly continuous. Evidence: PCS. Frequency: 1/2. (PMID:33833240)
- 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: 2/2. (PMID:33833240)
- Malnutrition (HP:0004395): A deficiency in the intake of energy and nutrients. Evidence: PCS. Frequency: 1/2. (PMID:33833240)
- EEG with burst suppression (HP:0010851): The burst suppression pattern in electroencephalography refers to a characteristic periodic pattern of low voltage (<10 microvolts) suppressed background and a relatively shorter pattern of higher amplitude slow, sharp, and spiking complexes. Evidence: PCS. Frequency: 1/2. (PMID:33833240)
- Epileptic spasm (HP:0011097): A sudden flexion, extension, or mixed extension-flexion of predominantly proximal and truncal muscles that is usually more sustained than a myoclonic movement but not as sustained as a tonic seizure. Limited forms may occur: Grimacing, head nodding, or subtle eye movements. Epileptic spasms frequently occur in clusters. Infantile spasms are the best known form, but spasms can occur at all ages. Evidence: PCS. Frequency: 1/2. (PMID:33833240)
- 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:33833240)
- 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: 1/2. (PMID:33833240)
- Mandibular prognathia (HP:0000303): Abnormal prominence of the chin related to increased length of the mandible. Evidence: PCS. Frequency: 4/4. (PMID:34909687)
- Myoclonus (HP:0001336): Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements. Evidence: PCS. Frequency: 5/5. (PMID:34909687)
These phenotypes are associated with the disease neurodevelopmental disorder with epilepsy and brain atrophy (OMIM:619971).