- Short stature (HP:0004322): A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms). Evidence: IEA. (OMIM:300352)
- Dystonia (HP:0001332): An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk. Evidence: TAS. (OMIM:300352)
- 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: IEA. (OMIM:300352)
- 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: 1/3. (PMID:27408820)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 13/13. (OMIM:300352;PMID:27408820)
- Aggressive behavior (HP:0000718): Behavior or an act aimed at harming a person, animal, or physical property (e.g., acts of physical violence; shouting, swearing, and using harsh language; slashing someone's tires). Evidence: IEA. (OMIM:300352)
- Constipation (HP:0002019): Infrequent or difficult evacuation of feces. Evidence: IEA. (OMIM:300352)
- 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: 3/3. (PMID:27408820;PMID:11326334)
- Tall stature (HP:0000098): A height above that which is expected according to age and gender norms. Evidence: IEA. (OMIM:300352)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 2/3. (PMID:27408820)
- Ileus (HP:0002595): Acute obstruction of the intestines preventing passage of the contents of the intestines. Evidence: IEA. (OMIM:300352)
- Hypoplasia of the corpus callosum (HP:0002079): Underdevelopment of the corpus callosum. Evidence: TAS. (OMIM:300352)
- 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: IEA. (OMIM:300352)
- 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:27408820;PMID:11326334)
- 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: TAS. (OMIM:300352)
- Elevated urinary creatine/creatinine ratio (HP:6000127): The ratio of creatine to creatinine concentration in the urine is above the upper limit of normal. Evidence: TAS. (OMIM:300352)
- Reduced brain creatine level by MRS (HP:0025051): A decrease in the level of creatine in the brain identified by magnetic resonance spectroscopy (MRS). Evidence: PCS. Frequency: 4/4. (PMID:27408820;PMID:11326334)
- X-linked recessive inheritance (HP:0001419): A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele. Evidence: PCS. (PMID:11326334)
- Speech apraxia (HP:0011098): A type of apraxia that is characterized by difficulty or inability to execute speech movements because of problems with coordination and motor problems, leading to incorrect articulation. An increase of errors with increasing word and phrase length may occur. Evidence: PCS. Frequency: 2/3. (PMID:27408820)
- Prolonged QT interval (HP:0001657): Increased time between the start of the Q wave and the end of the T wave as measured by the electrocardiogram (EKG). Evidence: PCS. Frequency: 7/18. (PMID:34050321)
- 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: TAS. (OMIM:300352)
- Hypertonia (HP:0001276): A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move. Evidence: PCS. Frequency: 1/3. (PMID:27408820)
- Hypermetropia (HP:0000540): An abnormality of refraction characterized by the ability to see objects in the distance clearly, while objects nearby appear blurry. Evidence: IEA. (OMIM:300352)
- Delayed myelination (HP:0012448): Delayed myelination. Evidence: TAS. (OMIM:300352)
- Motor delay (HP:0001270): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: IEA. (OMIM:300352)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 1/3. (PMID:27408820)
- 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: IEA. (OMIM:300352)
- Feeding difficulties in infancy (HP:0008872): Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention. Evidence: IEA. (OMIM:300352)
- Broad forehead (HP:0000337): Width of the forehead or distance between the frontotemporales is more than two standard deviations above the mean (objective); or apparently increased distance between the two sides of the forehead. Evidence: TAS. (OMIM:300352)
- Exotropia (HP:0000577): A form of strabismus with one or both eyes deviated outward. Evidence: IEA. (OMIM:300352)
- Narrow face (HP:0000275): Bizygomatic (upper face) and bigonial (lower face) width are both more than 2 standard deviations below the mean (objective); or, an apparent reduction in the width of the upper and lower face (subjective). Evidence: TAS. (OMIM:300352)
- Myopathic facies (HP:0002058): A facial appearance characteristic of myopathic conditions. The face appears expressionless with sunken cheeks, bilateral ptosis, and inability to elevate the corners of the mouth, due to muscle weakness. Evidence: TAS. (OMIM:300352)
- Axial hypotonia (HP:0008936): Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk. Evidence: PCS. Frequency: 1/3. (PMID:27408820)
- Broad-based gait (HP:0002136): An abnormal gait pattern in which persons stand and walk with their feet spaced widely apart. This is often a component of cerebellar ataxia. Evidence: PCS. Frequency: 1/3. (PMID:27408820)
- 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: 2/4. (PMID:27408820;PMID:11326334)
- Vomiting (HP:0002013): Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions. Evidence: IEA. (OMIM:300352)
- Pes cavus (HP:0001761): An increase in height of the medial longitudinal arch of the foot that does not flatten on weight bearing (i.e., a distinctly hollow form of the sole of the foot when it is bearing weight). Evidence: IEA. (OMIM:300352)
- Long face (HP:0000276): Facial height (length) is more than 2 standard deviations above the mean (objective); or, an apparent increase in the height (length) of the face (subjective). Evidence: TAS. (OMIM:300352)
- Gait disturbance (HP:0001288): The term gait disturbance can refer to any disruption of the ability to walk. Evidence: TAS. (OMIM:300352)
- Malar flattening (HP:0000272): Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation. Evidence: IEA. (OMIM:300352)
- Aganglionic megacolon (HP:0002251): An abnormality resulting from a lack of intestinal ganglion cells (i.e., an aganglionic section of bowel) that results in bowel obstruction with enlargement of the colon. Evidence: IEA. (OMIM:300352)
- Reduced social responsiveness (HP:0012760): A reduced ability to participate in the back-and-forth flow of social interaction appropriate to culture and developmental level, which is normally characterized by an influence of the behavior of one person on the behavior of another person. This results in difficulty interacting with others through emotional, physical, or verbal communication. Evidence: IEA. (OMIM:300352)
- Underfolded superior helices (HP:0008583): A condition in which the superior portion of the helix is folded over to a lesser degree than normal. Evidence: IEA. (OMIM:300352)
- Ptosis (HP:0000508): The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective). Evidence: TAS. (OMIM:300352)
- Poor hand-eye coordination (HP:0007057). Evidence: IEA. (OMIM:300352)
- Neonatal hypotonia (HP:0001319): Muscular hypotonia (abnormally low muscle tone) manifesting in the neonatal period. Evidence: IEA. (OMIM:300352)
- 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: IEA. (OMIM:300352)
- Mandibular prognathia (HP:0000303): Abnormal prominence of the chin related to increased length of the mandible. Evidence: IEA. (OMIM:300352)
- Elevated circulating creatine concentration (HP:0034291): An elevation above the normal range of creatine in the blood circulation. Evidence: PCS. Frequency: 1/1. (PMID:11326334)
These phenotypes are associated with the disease creatine transporter deficiency (OMIM:300352).