- Failure to thrive in infancy (HP:0001531). Evidence: PCS. Frequency: 2/4. (PMID:30824121)
- Mild intellectual disability (HP:0001256): Mild intellectual disability (ID) is defined as a type of ID characterized by mildly sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) the range of 50-69. Evidence: PCS. Frequency: 4/4. (PMID:30824121)
- Delayed CNS myelination (HP:0002188): Delayed myelination in the central nervous system. Evidence: PCS. Frequency: 1/4. (PMID:30824121)
- 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: PCS. Frequency: 1/4. (PMID:30824121)
- 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: PCS. Frequency: 2/4. (PMID:30824121)
- 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: 1/4. (PMID:30824121)
- Flexion contracture (HP:0001371): A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints. Evidence: PCS. Frequency: 1/4. (PMID:30824121)
- Talipes valgus (HP:0004684): Outward turning of the heel, resulting in clubfoot with the person walking on the inner part of the foot. Evidence: PCS. Frequency: 1/4. (PMID:30824121)
- 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: 1/4. (PMID:30824121)
- Chordee (HP:0000041): A congenital anomaly of the penis characterized by ventral (i.e., downward), lateral, or ventrolateral curvature of the shaft and glans penis of more than 30 degrees. Evidence: PCS. (PMID:30824121)
- Depression (HP:0000716): Frequently experiencing feelings of being down, miserable, and/or hopeless; struggling to recover from these moods; having a pessimistic outlook on the future; feeling a pervasive sense of shame; having a low self-worth; experiencing thoughts of suicide and engaging in suicidal behavior. Evidence: PCS. Frequency: 1/4. (PMID:30824121)
- Aortic root aneurysm (HP:0002616): An abnormal localized widening (dilatation) of the aortic root. Evidence: PCS. Frequency: 1/4. (PMID:30824121)
- Incoordination (HP:0002311): A deficit in coordination of muscle movements. Coordination is defined as the orchestrated movement of multiple body parts as required to accomplish intended actions, like walking. Evidence: PCS. Frequency: 1/4. (PMID:30824121)
- Submucous cleft hard palate (HP:0000176): Hard-palate submucous clefts are characterized by bony defects in the midline of the bony palate that are covered by the mucous membrane of the roof of the mouth. It may be possible to detect a submucous cleft hard palate upon palpation as a notch in the bony palate. Evidence: PCS. Frequency: 1/4. (PMID:30824121)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 2/4. (PMID:30824121)
- Hypoplasia of the corpus callosum (HP:0002079): Underdevelopment of the corpus callosum. Evidence: PCS. Frequency: 1/4. (PMID:30824121)
- 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. Frequency: 1/4. (PMID:30824121)
- Deeply set eye (HP:0000490): An eye that is more deeply recessed into the plane of the face than is typical. Evidence: PCS. Frequency: 1/4. (PMID:30824121)
- Dysdiadochokinesis (HP:0002075): A type of ataxia characterized by the impairment of the ability to perform rapidly alternating movements, such as pronating and supinating his or her hand on the dorsum of the other hand as rapidly as possible. Evidence: PCS. Frequency: 1/4. (PMID:30824121)
- Delayed gross motor development (HP:0002194): A type of motor delay characterized by a delay in acquiring the ability to control the large muscles of the body for walking, running, sitting, and crawling. Evidence: PCS. Frequency: 4/4. (PMID:30824121)
- Ankle clonus (HP:0011448): Clonus is an involuntary tendon reflex that causes repeated flexion and extension of the foot. Ankle clonus is tested by rapidly flexing the foot upward. Evidence: PCS. Frequency: 1/4. (PMID:30824121)
- Generalized limb muscle atrophy (HP:0009055): Generalized (unlocalized) atrophy affecting muscles of the limbs in both proximal and distal locations. Evidence: PCS. Frequency: 1/4. (PMID:30824121)
- 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:30824121)
- Compulsive behaviors (HP:0000722): Behavior that consists of repetitive acts, characterized by the feeling that one "has to" perform them, while being aware that these acts are not in line with one's overall goal. Evidence: PCS. Frequency: 1/4. (PMID:30824121)
- Type II diabetes mellitus (HP:0005978): A type of diabetes mellitus initially characterized by insulin resistance and hyperinsulinemia and subsequently by glucose interolerance and hyperglycemia. Evidence: PCS. Frequency: 2/4. (PMID:30824121)
- Hypospadias (HP:0000047): Abnormal position of urethral meatus on the ventral penile shaft (underside) characterized by displacement of the urethral meatus from the tip of the glans penis to the ventral surface of the penis, scrotum, or perineum. Evidence: PCS. (PMID:30824121)
- Narrow forehead (HP:0000341): Width of the forehead or distance between the frontotemporales is more than two standard deviations below the mean (objective); or apparently narrow intertemporal region (subjective). Evidence: PCS. Frequency: 1/4. (PMID:30824121)
- 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: 1/4. (PMID:30824121)
- Sleep disturbance (HP:0002360): An abnormal pattern in the quality, quantity, or characteristics of sleep. Evidence: PCS. Frequency: 1/4. (PMID:30824121)
- Narrow nose (HP:0000460): Interalar distance more than 2 SD below the mean for age, or alternatively, an apparently decreased width of the nasal base and alae. Evidence: PCS. Frequency: 2/4. (PMID:30824121)
- Delayed fine motor development (HP:0010862): A type of motor delay characterized by a delay in acquiring the ability to control the fingers and hands. Evidence: PCS. Frequency: 4/4. (PMID:30824121)
- Sparse hair (HP:0008070): Reduced density of hairs. Evidence: PCS. (PMID:30824121)
- Irritability (HP:0000737): An emotional state characterized by negative feelings of heightened frustration, annoyance, or feeling upset, often triggered by internal factors (e.g., fatigue, hunger, unfulfilled desires) or external factors (e.g., social or environmental challenges). Irritability may be unpredictable, and is accompanied by a lowered threshold for emotional reactivity and observable features (speech, facial expressions, or psychomotor activity). Evidence: PCS. Frequency: 1/4. (PMID:30824121)
- 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: PCS. Frequency: 1/4. (PMID:30824121)
- Brisk reflexes (HP:0001348): Tendon reflexes that are noticeably more active than usual (conventionally denoted 3+ on clinical examination). Brisk reflexes may or may not indicate a neurological lesion. They are distinguished from hyperreflexia by the fact that hyerreflexia is characterized by hyperactive repeating (clonic) reflexes, which are considered to be always abnormal. Evidence: PCS. Frequency: 1/4. (PMID:30824121)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: PCS. Frequency: 1/4. Onset: Young adult onset (HP:0011462). (PMID:30824121)
- 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: 2/4. (PMID:30824121)
- Fine hair (HP:0002213): Hair that is fine or thin to the touch. Evidence: PCS. Frequency: 3/4. (PMID:30824121)
- 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: 4/4. (PMID:30824121)
- 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: 1/4. (PMID:30824121)
- 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: PCS. Frequency: 1/4. (PMID:30824121)
- Brittle hair (HP:0002299): Fragile, easily breakable hair, i.e., with reduced tensile strength. Evidence: PCS. (PMID:30824121)
- Small for gestational age (HP:0001518): Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age. Evidence: PCS. Frequency: 1/4. Onset: Congenital onset (HP:0003577). (PMID:30824121)
- Pendular nystagmus (HP:0012043): Rhythmic, involuntary sinusoidal oscillations of one or both eyes. The waveform of pendular nystagmus may occur in any direction. Evidence: PCS. Frequency: 1/4. (PMID:30824121)
- Abnormal pyramidal sign (HP:0007256): Functional neurological abnormalities related to dysfunction of the pyramidal tract. Evidence: PCS. Frequency: 1/4. (PMID:30824121)
- High forehead (HP:0000348): An abnormally increased height of the forehead. Evidence: IEA. Frequency: 1/4. (PMID:30824121)
- Delayed puberty (HP:0000823): Passing the age when puberty normally occurs with no physical or hormonal signs of the onset of puberty. Evidence: PCS. Frequency: 1/4. (PMID:30824121)
- Intrauterine growth retardation (HP:0001511): An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age. Evidence: PCS. Frequency: 2/4. Onset: Antenatal onset (HP:0030674). (PMID:30824121)
- 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: 1/4. (PMID:30824121)
- Atrial septal defect (HP:0001631): Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum. Evidence: PCS. Frequency: 1/4. (PMID:30824121)
These phenotypes are associated with the disease microcephaly, developmental delay, and brittle hair syndrome (OMIM:618891).