- 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: 1/5. (PMID:39003500)
- Myopathy (HP:0003198): A disorder of muscle unrelated to impairment of innervation or neuromuscular junction. Evidence: PCS. Frequency: 2/2. (PMID:39003500)
- 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: 1/5. (PMID:39003500)
- 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: 4/4. (PMID:39003500)
- Distal muscle weakness (HP:0002460): Reduced strength of the musculature of the distal extremities. Evidence: PCS. Frequency: 2/2. (PMID:39003500)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 7/7. (PMID:39003500)
- Avascular necrosis (HP:0010885): A disease where there is cellular death (necrosis) of bone components due to interruption of the blood supply. Evidence: PCS. Frequency: 1/1. (PMID:39003500)
- Small hypothenar eminence (HP:0010487): Reduced muscle mass on the ulnar side of the palm, that is, reduction in size of the hypothenar eminence. Evidence: PCS. Frequency: 2/2. (PMID:39003500)
- Decreased heart rate variability (HP:0031861): Reduced variation of beat-to-beat intervals of the heart that occurs in conjunction with the respiratory cycle. Evidence: PCS. Frequency: 2/6. (PMID:39003500)
- Abnormality of circulating cortisol level (HP:0011731): An abnormality of the concentration of cortisol in the blood. Evidence: PCS. Frequency: 0/2. (PMID:39003500)
- Tongue atrophy (HP:0012473): Wasting of the tongue. Evidence: PCS. Frequency: 2/4. (PMID:39003500)
- 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: PCS. Frequency: 1/2. (PMID:39003500)
- Coxa vara (HP:0002812): Coxa vara includes all forms of decrease of the femoral neck shaft angle (the angle between the neck and the shaft of the femur) to less than 120 degrees. Evidence: PCS. Frequency: 1/1. (PMID:39003500)
- Postnatal growth retardation (HP:0008897): Slow or limited growth after birth. Evidence: PCS. Frequency: 4/7. (PMID:39003500)
- Hyporeflexia of upper limbs (HP:0012391): Reduced intensity of muscle tendon reflexes in the upper limbs. Reflexes are elicited by stretching the tendon of a muscle, e.g., by tapping. Evidence: PCS. Frequency: 1/4. (PMID:39003500)
- Muscle weakness (HP:0001324): Reduced strength of muscles. Evidence: PCS. Frequency: 1/2. (PMID:39003500)
- 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: 1/3. (PMID:39003500)
- Downslanted palpebral fissures (HP:0000494): The palpebral fissure inclination is more than two standard deviations below the mean. Evidence: PCS. Frequency: 2/4. (PMID:39003500)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 1/5. (PMID:39003500)
- Few cafe-au-lait spots (HP:0007429): The presence of two to five cafe-au-lait macules. Evidence: PCS. Frequency: 1/1. (PMID:39003500)
- EMG: neuropathic changes (HP:0003445): The presence of characteristic findings of denervation on electromyography (fibrillations, positive sharp waves, and giant motor unit potentials). Evidence: PCS. Frequency: 1/1. (PMID:39003500)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: PCS. Frequency: 1/4. (PMID:39003500)
- Interictal EEG abnormality (HP:0025373): Interictal refers to a period of time between epileptic seizures. Electroencephalographic (EEG) patterns are important in the differential diagnosis of epilepsy, and the EEG is almost always abnormal during a seizure. Some persons with seizures may show EEG abnormalities between seizures, while others do not. In some cases, multiple interictal EEGs must be recorded before an abnormality is observed. In most cases the electrographic pattern of seizure onset is completely different from the activity recorded during interictal discharge. Evidence: PCS. Frequency: 2/6. (PMID:39003500)
- 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: 2/3. (PMID:39003500)
- Upper limb muscle weakness (HP:0003484): Weakness of the muscles of the arms. Evidence: PCS. Frequency: 2/2. (PMID:39003500)
- 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: 4/4. (PMID:39003500)
- 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: 3/3. (PMID:39003500)
- Tapered finger (HP:0001182): The gradual reduction in girth of the finger from proximal to distal. Evidence: PCS. Frequency: 3/3. (PMID:39003500)
- Fatigue (HP:0012378): A subjective feeling of tiredness characterized by a lack of energy and motivation. Evidence: PCS. Frequency: 2/2. (PMID:39003500)
- Pes valgus (HP:0008081): An outward (valgus) deviation of the calcaneus relative to the longitudinal axis of the lower leg at the talocalcaneal (subtalar) joint, such that the heel is everted. Evidence: PCS. Frequency: 1/1. (PMID:39003500)
- Knee contracture (HP:0034671): Lack of full passive range of motion (restrictions in flexion, extension, or other movements) of the knee joint resulting from structural changes of non-bony tissues, such as muscles, tendons, ligaments, joint capsules and/or skin. Evidence: PCS. Frequency: 1/1. (PMID:39003500)
- 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:39003500)
- Absent Achilles reflex (HP:0003438): Absence of the Achilles reflex (also known as the ankle jerk reflex), which can normally be elicited by tapping the tendon is tapped while the foot is dorsiflexed. Evidence: PCS. Frequency: 2/6. (PMID:39003500)
- 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: 1/1. (PMID:39003500)
- Elbow contracture (HP:0034391): A limitation in the passive range of motion of the elbow 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. Evidence: PCS. Frequency: 1/1. (PMID:39003500)
- Chronic diarrhea (HP:0002028): The presence of chronic diarrhea, which is usually taken to mean diarrhea that has persisted for over 4 weeks. Evidence: PCS. Frequency: 1/1. (PMID:39003500)
- Hypernasal speech (HP:0001611): A type of speech characterized by the presence of an abnormally increased nasal airflow during speech associated with structural abnormality of the nasal passages. Evidence: PCS. Frequency: 5/5. (PMID:39003500)
- Alacrima (HP:0000522): Absence of tear secretion. Evidence: PCS. Frequency: 3/3. (PMID:39003500)
- Hyperkeratosis (HP:0000962): Hyperkeratosis is a histopathological term defining a thickened stratum corneum and may be present in many different skin conditions, with many possible overlaps. Hyperkeratosis refers to the increased thickness of the stratum corneum, the outer layer of the skin. Hyperkeratosis is subclassified as orthokeratotic or parakeratotic. Orthokeratotic hyperkeratosis refers to the thickening of the keratin layer with preserved keratinocyte maturation, while parakeratotic hyperkeratosis shows retained nuclei as a sign of delayed maturation of keratinocytes. Evidence: PCS. Frequency: 2/2. (PMID:39003500)
- Preauricular skin tag (HP:0000384): A rudimentary tag of skin often containing ear tissue including a core of cartilage and located just anterior to the auricle (outer part of the ear). Evidence: PCS. Frequency: 1/1. (PMID:39003500)
- Distal amyotrophy (HP:0003693): Muscular atrophy affecting muscles in the distal portions of the extremities. Evidence: PCS. Frequency: 1/1. (PMID:39003500)
- Bilateral facial palsy (HP:0430025): Two-sided or bilateral weakness of the muscles of facial expression and eye closure. Evidence: PCS. Frequency: 0/3. (PMID:39003500)
- Polyneuropathy (HP:0001271): A generalized disorder of peripheral nerves. Evidence: PCS. Frequency: 1/1. (PMID:39003500)
- 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: 0/4. (PMID:39003500)
- Weakness of facial musculature (HP:0030319): Reduced strength of one or more muscles innervated by the facial nerve (the seventh cranial nerve). Evidence: PCS. Frequency: 3/4. (PMID:39003500)
- Lower limb muscle weakness (HP:0007340): Weakness of the muscles of the legs. Evidence: PCS. Frequency: 2/2. (PMID:39003500)
- Cerebral visual impairment (HP:0100704): A form of loss of vision caused by damage to the visual cortex rather than a defect in the eye. Evidence: PCS. Frequency: 1/1. (PMID:39003500)
- Demyelinating motor neuropathy (HP:0007220): Demyelination of peripheral motor nerves. Evidence: PCS. Frequency: 1/1. (PMID:39003500)
- Abnormal circulating adrenocorticotropin concentration (HP:0011043): An abnormal concentration of corticotropin in the blood. Evidence: PCS. Frequency: 0/2. (PMID:39003500)
- Anxiety (HP:0000739): Intense feelings of nervousness, tension, or panic often arise in response to interpersonal stresses. There is worry about the negative effects of past unpleasant experiences and future negative possibilities. Individuals may feel fearful, apprehensive, or threatened by uncertainty, and they may also have fears of falling apart or losing control. Evidence: PCS. Frequency: 1/2. (PMID:39003500)
- Blindness (HP:0000618): Blindness is the condition of lacking visual perception defined as a profound reduction in visual perception. On the 6m visual acuity scale, blindness is defined as less than 3/60. On the 20ft visual acuity scale, blindness is defined as less than 20/400. On the decimal visual acuity scale, blindness is defined as less than 0.05. Blindness is typically characterized by a visual field of no greater than 10 degrees in radius around central fixation. Evidence: PCS. Frequency: 1/1. (PMID:39003500)
- Tongue fasciculations (HP:0001308): Fasciculations or fibrillation affecting the tongue muscle. Evidence: PCS. Frequency: 2/2. (PMID:39003500)
- Chest pain (HP:0100749): An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the chest. Evidence: PCS. Frequency: 1/6. (PMID:39003500)
- Recurrent pneumonia (HP:0006532): An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia. Evidence: PCS. Frequency: 2/7. (PMID:39003500)
- Aspiration (HP:0002835): Inspiration of a foreign object into the airway. Evidence: PCS. Frequency: 1/1. (PMID:39003500)
- High palate (HP:0000218): Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective). Evidence: PCS. Frequency: 3/4. (PMID:39003500)
- Frequent falls (HP:0002359). Evidence: PCS. Frequency: 1/1. (PMID:39003500)
- Hyperreflexia (HP:0001347): Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles. Evidence: PCS. Frequency: 1/1. (PMID:39003500)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: PCS. Frequency: 3/3. (PMID:39003500)
- Long nose (HP:0003189): Distance from nasion to subnasale more than two standard deviations above the mean, or alternatively, an apparently increased length from the nasal root to the nasal base. Evidence: PCS. Frequency: 2/4. (PMID:39003500)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: PCS. Frequency: 1/1. (PMID:39003500)
- 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: 3/3. (PMID:39003500)
- 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: 1/1. (PMID:39003500)
- Delayed ability to walk (HP:0031936): A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months. Evidence: PCS. Frequency: 5/6. (PMID:39003500)
- Gait disturbance (HP:0001288): The term gait disturbance can refer to any disruption of the ability to walk. Evidence: PCS. Frequency: 1/1. (PMID:39003500)
- Achalasia (HP:0002571): A disorder of esophageal motility characterized by the inability of the lower esophageal sphincter to relax during swallowing and by inadequate or lacking peristalsis in the lower half of the body of the esophagus. Evidence: PCS. Frequency: 3/6. (PMID:39003500)
- Episodic vomiting (HP:0002572): Paroxysmal, recurrent episodes of vomiting. Evidence: PCS. Frequency: 3/3. (PMID:39003500)
- Urolithiasis (HP:0034368): Renal stones are formed within the kidneys, and this is called nephrolithiasis. Urolithiasis is a condition that occurs when these stones exit the renal pelvis and move into the remainder of the urinary collecting system, which includes the ureters, bladder, and urethra. Evidence: PCS. Frequency: 2/7. (PMID:39003500)
- Dilation of Virchow-Robin spaces (HP:0012520): Increased dimensions of the Virchow-Robin spaces (also known as perivascular spaces), which surround the walls of vessels as they course from the subarachnoid space through the brain parenchyma. Perivascular spaces are commonly microscopic, and not visible on conventional neuroimaging. This term refers to an increase of size of these spaces such that they are visible on neuroimaging (usually magnetic resonance imaging). The dilatations are regular cavities that always contain a patent artery. Evidence: PCS. Frequency: 2/2. (PMID:39003500)
- Peripheral neuropathy (HP:0009830): Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course. Evidence: PCS. Frequency: 2/2. (PMID:39003500)
- Small hand (HP:0200055): Disproportionately small hand. Evidence: PCS. Frequency: 1/1. (PMID:39003500)
- Hyporeflexia of lower limbs (HP:0002600): Reduced intensity of muscle tendon reflexes in the lower limbs. Reflexes are elicited by stretching the tendon of a muscle, e.g., by tapping. Evidence: PCS. Frequency: 2/6. (PMID:39003500)
These phenotypes are associated with the disease neurodevelopmental disorder with achalasia, polyneuropathy, and alacrima (OMIM:621328).