Phenotypes associated with the disease brain abnormalities, neurodegeneration, and dysosteosclerosis (OMIM:618476):
- Epicanthus (HP:0000286): A fold of skin starting above the medial aspect of the upper eyelid and arching downward to cover, pass in front of and lateral to the medial canthus. Evidence: PCS. Frequency: 1/4. (PMID:30982609)
- Mutism (HP:0002300): Complete lack of speech or verbal communication in a person despite attempts to engage in conversation. Mutism as a phenomena assumes the individual has previous capacity for speech and in the pediatric population it assumes that the person is past the age of typical language development. Evidence: IEA. (OMIM:618476)
- Poor speech (HP:0002465). Evidence: IEA. (OMIM:618476)
- 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:30982609)
- Tented upper lip vermilion (HP:0010804): Triangular appearance of the oral aperture with the apex in the midpoint of the upper vermilion and the lower vermilion forming the base. Evidence: PCS. Frequency: 1/4. (PMID:30982609)
- 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. (PMID:30982609)
- Diaphyseal sclerosis (HP:0003034): An elevation in bone density in one or more diaphyses. Sclerosis is normally detected on a radiograph as an area of increased opacity. Evidence: PCS. Frequency: 4/4. (PMID:30982609)
- Rigidity (HP:0002063): Continuous involuntary sustained muscle contraction. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity. Evidence: PCS. Frequency: 1/4. (PMID:30982609)
- 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. (PMID:30982609)
- Neurodegeneration (HP:0002180): Progressive loss of neural cells and tissue. Evidence: IEA. (OMIM:618476)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: PCS. Frequency: 1/4. (PMID:30982609)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. (PMID:30982609)
- Periventricular heterotopia (HP:0007165): A form of gray matter heterotopia were the mislocalized gray matter is typically located periventricularly, also sometimes called subependymal heterotopia. Periventricular means beside the ventricles. This is by far the most common location for heterotopia. Subependymal heterotopia present in a wide array of variations. There can be a small single node or a large number of nodes, can exist on either or both sides of the brain at any point along the higher ventricle margins, can be small or large, single or multiple, and can form a small node or a large wavy or curved mass. Evidence: IEA. (OMIM:618476)
- Hydrocephalus (HP:0000238): Hydrocephalus is an active distension of the ventricular system of the brain resulting from inadequate passage of CSF from its point of production within the cerebral ventricles to its point of absorption into the systemic circulation. Evidence: PCS. Frequency: 2/4. Onset: Congenital onset (HP:0003577). (PMID:30982609)
- 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: 1/4. (PMID:30982609)
- Spastic tetraplegia (HP:0002510): Spastic paralysis affecting all four limbs. Evidence: IEA. (OMIM:618476)
- Craniofacial osteosclerosis (HP:0005464): Abnormally increased density of craniofacial bone tissue. Evidence: PCS. Frequency: 2/4. (PMID:30982609)
- 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. (PMID:30982609)
- 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: 1/4. (PMID:30982609)
- Increased skull ossification (HP:0004330): An increase in the magnitude or amount of ossification of the skull. Evidence: PCS. Frequency: 4/4. (PMID:30982609)
- Sclerotic vertebral body (HP:0100861): Increase in bone density of the vertebral body. Evidence: PCS. Frequency: 2/4. (PMID:30982609)
- Platyspondyly (HP:0000926): A flattened vertebral body shape with reduced distance between the vertebral endplates. Evidence: PCS. Frequency: 4/4. (PMID:30982609)
- 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:30982609)
- Long eyelashes (HP:0000527): Mid upper eyelash length >10 mm or increased length of the eyelashes (subjective). Evidence: PCS. Frequency: 1/4. (PMID:30982609)
- 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: 1/4. (PMID:30982609)
- Hypocalcemia (HP:0002901): The concentration of calcium in the blood circulation is below the lower limit of normal. Evidence: IEA. Frequency: Very rare (HP:0040284). (OMIM:618476)
- 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: 1/4. (PMID:30982609)
- 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: 2/4. (PMID:30982609)
- 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: 3/4. (PMID:30982609)
- Metaphyseal widening (HP:0003016): Abnormal widening of the metaphyseal regions of long bones. Evidence: PCS. Frequency: 4/4. (PMID:30982609)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. (PMID:30982609)
- Bell-shaped thorax (HP:0001591): The rib cage has the shape of a wide mouthed bell. That is, the superior portion of the rib cage is constricted, followed by a convex region, and the inferior portion of the rib cage expands again to have a large diameter. Evidence: PCS. Frequency: 1/4. (PMID:30982609)
- Agenesis of corpus callosum (HP:0001274): Absence of the corpus callosum as a result of the failure of the corpus callosum to develop, which can be the result of a failure in any one of the multiple steps of callosal development including cellular proliferation and migration, axonal growth or glial patterning at the midline. Evidence: PCS. Frequency: 1/4. (PMID:30982609)
- Enlarged cisterna magna (HP:0002280): Increase in size of the cisterna magna, one of three principal openings in the subarachnoid space between the arachnoid and pia mater, located between the cerebellum and the dorsal surface of the medulla oblongata. Evidence: PCS. Frequency: 2/4. (PMID:30982609)
- Cognitive impairment (HP:0100543): Abnormal cognition is characterized by deficits in thinking, reasoning, or remembering. Evidence: PCS. Frequency: 1/4. (PMID:30982609)
- Osteopetrosis (HP:0011002): Abnormally increased formation of dense trabecular bone tissue. Despite the increased density of bone tissue, osteopetrotic bones tend to be more fracture-prone than normal. Evidence: PCS. Frequency: 1/4. (PMID:30982609)
- Bulbous nose (HP:0000414): Increased volume and globular shape of the anteroinferior aspect of the nose. Evidence: PCS. Frequency: 1/4. (PMID:30982609)
- Dandy-Walker malformation (HP:0001305): A congenital brain malformation typically characterized by incomplete formation of the cerebellar vermis, dilation of the fourth ventricle, and enlargement of the posterior fossa. In layman's terms, Dandy Walker malformation is a cyst in the cerebellum (typically symmetrical) that is involved with the fourth ventricle. This may interfere with the ability to drain cerebrospinal fluid from the brain, resulting in hydrocephalus. Dandy Walker cysts are formed during early embryonic development, while the brain forms. The cyst in the cerebellum typically has several blood vessels running through it connecting to the brain, thereby prohibiting surgical removal. Evidence: PCS. Frequency: 1/4. (PMID:30982609)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: PCS. Frequency: 4/4. (PMID:30982609)
- Cerebral calcification (HP:0002514): The presence of calcium deposition within the cerebrum. Evidence: PCS. Frequency: 4/4. (PMID:30982609)
- 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: IEA. (OMIM:618476)
- Mental deterioration (HP:0001268): Loss of previously present mental abilities, generally in adults. Evidence: IEA. (OMIM:618476)
- Erlenmeyer flask deformity of the femurs (HP:0004975): Flaring of distal femur. Evidence: PCS. Frequency: 1/4. (PMID:30982609)
- Hyperreflexia (HP:0001347): Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles. Evidence: PCS. Frequency: 1/4. (PMID:30982609)
- Juvenile onset (HP:0003621): Onset of signs or symptoms of disease between the age of 5 and 15 years. Evidence: PCS. (PMID:30982609)
- 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: IEA. (OMIM:618476)
- Gait disturbance (HP:0001288): The term gait disturbance can refer to any disruption of the ability to walk. Evidence: PCS. Frequency: 1/4. (PMID:30982609)
- 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: 1/4. (PMID:30982609)
- Kyphosis (HP:0002808): Exaggerated anterior convexity of the thoracic vertebral column. Evidence: PCS. Frequency: 1/4. (PMID:30982609)
- Chiari type I malformation (HP:0007099): Arnold-Chiari type I malformation refers to a relatively mild degree of herniation of the posteroinferior region of the cerebellum (the cerebellar tonsils) into the cervical canal with little or no displacement of the fourth ventricle. It is characterized by one or both pointed (not rounded) cerebellar tonsils that project 5 mm below the foramen magnum, measured by a line drawn from the basion to the opisthion (McRae Line). Evidence: PCS. Frequency: 1/4. (PMID:30982609)
- Hyperintensity of cerebral white matter on MRI (HP:0030890): A brighter than expected signal on magnetic resonance imaging emanating from the cerebral white matter. Evidence: PCS. Frequency: 2/4. (PMID:30982609)
- 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: 1/4. (PMID:30982609)