- 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: IEA. (OMIM:617481)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. (PMID:28334956)
- Progressive (HP:0003676): Applies to a disease manifestation that increases in scope or severity over the course of time, i.e., that worsens with age. Evidence: PCS. (PMID:28334956)
- Sloping forehead (HP:0000340): Inclination of the anterior surface of the forehead from the vertical more than two standard deviations above the mean (objective); or apparently excessive posterior sloping of the forehead in a lateral view. Evidence: IEA. (OMIM:617481)
- Narrow palate (HP:0000189): Width of the palate more than 2 SD below the mean (objective) or apparently decreased palatal width (subjective). Evidence: IEA. Frequency: Very rare (HP:0040284). (OMIM:617481)
- Inability to walk (HP:0002540): Incapability to ambulate. Evidence: PCS. Frequency: 15/15. (PMID:28334956)
- Delayed CNS myelination (HP:0002188): Delayed myelination in the central nervous system. Evidence: PCS. Frequency: 5/13. (PMID:28334956)
- 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: 2/13. (PMID:28334956)
- Cerebral cortical atrophy (HP:0002120): Atrophy of the cortex of the cerebrum. Evidence: PCS. Frequency: 5/13. (PMID:28334956)
- 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: 6/13. (PMID:28334956)
- 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: 15/15. (PMID:28334956)
- 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: 15/15. (PMID:28334956)
- Cataract (HP:0000518): A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule. Evidence: PCS. Frequency: 3/9. Onset: Congenital onset (HP:0003577). (PMID:28334956)
- Protruding ear (HP:0000411): Angle formed by the plane of the ear and the mastoid bone greater than the 97th centile for age (objective); or, outer edge of the helix more than 2 cm from the mastoid at the point of maximum distance (objective). Evidence: IEA. (OMIM:617481)
- Hyperreflexia (HP:0001347): Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles. Evidence: PCS. Frequency: 12/15. (PMID:28334956)
- Skeletal muscle atrophy (HP:0003202): The presence of skeletal muscular atrophy (which is also known as amyotrophy). Evidence: PCS. Frequency: 7/8. (PMID:28334956)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 15/15. (PMID:28334956)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: IEA. (OMIM:617481)
- Talipes equinovarus (HP:0001762): Talipes equinovarus (also called clubfoot) typically has four main components: inversion and adduction of the forefoot; inversion of the heel and hindfoot; equinus (limitation of extension) of the ankle and subtalar joint; and internal rotation of the leg. Evidence: IEA. (OMIM:617481)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: PCS. Frequency: 15/15. (PMID:28334956)
- Hypoplasia of the corpus callosum (HP:0002079): Underdevelopment of the corpus callosum. Evidence: PCS. Frequency: 4/13. (PMID:28334956)
- Spastic tetraparesis (HP:0001285): Spastic weakness affecting all four limbs. Evidence: PCS. Frequency: 14/15. (PMID:28334956)
- 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: 15/15. (PMID:28334956)
- Joint contracture (HP:0034392): A limitation in the passive range of motion of a joint resulting from loss of elasticity in the periarticular tissues owing to structural changes of non-bony tissues, such as muscles, tendons, ligaments, joint capsules or skin. A contracture prevents movement of the associated body part. Evidence: PCS. Frequency: 7/8. (PMID:28334956)
- 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:28334956)
- Decreased fetal movement (HP:0001558): An abnormal reduction in quantity or strength of fetal movements. Evidence: IEA. (OMIM:617481)
- Optic atrophy (HP:0000648): Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy. Evidence: PCS. Frequency: 2/4. (PMID:28334956)
- Macrotia (HP:0000400): Median longitudinal ear length greater than two standard deviations above the mean and median ear width greater than two standard deviations above the mean (objective); or, apparent increase in length and width of the pinna (subjective). Evidence: IEA. (OMIM:617481)
- 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: 13/15. (PMID:28334956)
- Proptosis (HP:0000520): An eye that is protruding anterior to the plane of the face to a greater extent than is typical. Evidence: IEA. (OMIM:617481)
- Abnormal cerebral white matter morphology (HP:0002500): An abnormality of the cerebral white matter. Evidence: PCS. Frequency: 5/13. (PMID:28334956)
These phenotypes are associated with the disease neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies (OMIM:617481).