Phenotypes associated with the disease hypotonia, infantile, with psychomotor retardation and characteristic facies 3 (OMIM:616900):
- Encephalopathy (HP:0001298): Encephalopathy is a term that means brain disease, damage, or malfunction. In general, encephalopathy is manifested by an altered mental state. Evidence: PCS. (PMID:27040692)
- Corneal opacity (HP:0007957): A reduction of corneal clarity. Evidence: PCS. Frequency: 1/13. (PMID:27040691)
- Dysplastic corpus callosum (HP:0006989): Dysplasia and dysgenesis of the corpus callosum are nonspecific descriptions that imply defective development of the corpus callosum. The term dysplasia is applied when the morphology of the corpus callosum is altered as a congenital trait. For instance, the corpus callosum may be hump-shaped, kinked, or a striped corpus callosum that lacks an anatomically distinct genu and splenium. Evidence: PCS. (PMID:27040692)
- Hearing impairment (HP:0000365): A decreased magnitude of the sensory perception of sound. Evidence: PCS. Frequency: 1/24. (PMID:27040691;PMID:27040692;PMID:36522252)
- Strabismus (HP:0000486): A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error. Evidence: PCS. Frequency: 7/11. (PMID:30103036;PMID:27275012;PMID:36522252)
- Exaggerated cupid's bow (HP:0002263): More pronounced paramedian peaks and median notch of the Cupid's bow. Evidence: PCS. Frequency: 6/7. (PMID:27040692;PMID:37876076;PMID:36273129)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 7/20. (PMID:37876076;PMID:30103036;PMID:27275012;PMID:29283439;PMID:36522252)
- Generalized hypotonia (HP:0001290): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: PCS. Frequency: 6/6. (PMID:36522252)
- Multifocal epileptiform discharges (HP:0010841): An abnormality in cerebral electrical activity recorded along the scalp by electroencephalography (EEG) and being identified at multiple locations (foci). Evidence: PCS. Frequency: 6/11. (PMID:29283439;PMID:36522252)
- Thin corpus callosum (HP:0033725): An abnormally thin corpus callous, due to atrophy, hypoplasia or agenesis. This term is intended to be used in situations where it is not known if thinning of the corpus callosum (for instance, as visualized by magnetic resonance tomography) is due to abnormal development (e.g. a leukodystrophy) or atrophy following normal development (e.g. neurodegeneration). Evidence: PCS. Frequency: 7/7. (PMID:32363625;PMID:29283439)
- 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: 1/5. (PMID:27040692)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: PCS. Frequency: 2/6. (PMID:36522252)
- Thick vermilion border (HP:0012471): Increased width of the skin of vermilion border region of upper lip. Evidence: PCS. Frequency: 2/15. (PMID:27040691;PMID:37876076;PMID:36273129)
- Overlapping toe (HP:0001845): Describes a foot digit resting on the dorsal surface of an adjacent digit when the foot is at rest. Initially clawing may be dynamic and only noticeable on walking. Over time the plantar plate tears, subluxation occurs at the metatarsophalangeal joint (MTPJ), and the deformity becomes permanent. Evidence: PCS. Frequency: 3/3. (PMID:27275012)
- 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: 2/6. (PMID:36522252)
- 11 pairs of ribs (HP:0000878): Presence of only 11 pairs of ribs. Evidence: PCS. Frequency: 2/18. (PMID:27040691;PMID:27040692)
- Neonatal onset (HP:0003623): Onset of signs or symptoms of disease within the first 28 days of life. Evidence: PCS. Frequency: 4/5. (PMID:27275012;PMID:32363625)
- Highly arched eyebrow (HP:0002553): Increased height of the central portion of the eyebrow, forming a crescent, semicircular, or inverted U shape. Evidence: PCS. Frequency: 9/12. (PMID:27040692;PMID:36273129;PMID:36522252)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 1/26. (PMID:27040691;PMID:27040692;PMID:29283439)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: PCS. Frequency: 18/24. (PMID:27040691;PMID:37876076;PMID:30103036;PMID:32363625;PMID:36522252)
- Hypertriglyceridemia (HP:0002155): An abnormal increase in the level of triglycerides in the blood. Evidence: PCS. Frequency: 3/6. (PMID:36522252)
- Hypercholesterolemia (HP:0003124): An increased concentration of cholesterol in the blood. Evidence: PCS. Frequency: 3/6. (PMID:36522252)
- Deeply set eye (HP:0000490): An eye that is more deeply recessed into the plane of the face than is typical. Evidence: PCS. Frequency: 6/21. (PMID:27040691;PMID:27040692;PMID:30103036;PMID:36273129)
- Tube feeding (HP:0033454): Feeding problem necessitating food and nutrient delivery via a tube. Evidence: PCS. Frequency: 7/10. (PMID:27040692;PMID:36522252)
- 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: 5/5. (PMID:27040692)
- Tapered finger (HP:0001182): The gradual reduction in girth of the finger from proximal to distal. Evidence: PCS. Frequency: 1/2. (PMID:32363625)
- Small basal ganglia (HP:0012697): Decreased size of the basal ganglia. Evidence: PCS. (PMID:27040692)
- 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: 1/2. (PMID:32363625)
- Pectus excavatum (HP:0000767): A defect of the chest wall characterized by a depression of the sternum, giving the chest ("pectus") a caved-in ("excavatum") appearance. Evidence: PCS. Frequency: 1/1. (PMID:36273129)
- 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:27040692)
- Partial agenesis of the corpus callosum (HP:0001338): A partial failure of the development of the corpus callosum. Evidence: PCS. Frequency: 1/6. (PMID:29283439)
- Long eyelashes (HP:0000527): Mid upper eyelash length >10 mm or increased length of the eyelashes (subjective). Evidence: PCS. Frequency: 1/14. (PMID:27040691;PMID:36273129)
- Proptosis (HP:0000520): An eye that is protruding anterior to the plane of the face to a greater extent than is typical. Evidence: PCS. Frequency: 3/3. (PMID:27275012)
- Brachycephaly (HP:0000248): An abnormality of skull shape characterized by a decreased anterior-posterior diameter. That is, a cephalic index greater than 81%. Alternatively, an apparently shortened anteroposterior dimension (length) of the head compared to width. Evidence: PCS. Frequency: 5/6. (PMID:37876076;PMID:30103036;PMID:27275012)
- Low-set ears (HP:0000369): Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear. Evidence: PCS. Frequency: 1/6. (PMID:36522252)
- 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: 14/16. (PMID:27040692;PMID:37876076;PMID:30103036;PMID:29283439)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 12/15. (PMID:36273129;PMID:29283439;PMID:36522252)
- 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: PCS. Frequency: 2/15. (PMID:27040691;PMID:37876076;PMID:36273129)
- Upslanted palpebral fissure (HP:0000582): The palpebral fissure inclination is more than two standard deviations above the mean for age (objective); or, the inclination of the palpebral fissure is greater than typical for age. Evidence: PCS. Frequency: 1/15. (PMID:27040691;PMID:37876076;PMID:36273129)
- Long philtrum (HP:0000343): Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border. Evidence: PCS. Frequency: 3/16. (PMID:27040691;PMID:30103036;PMID:36273129)
- Anteverted nares (HP:0000463): Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip). Evidence: PCS. Frequency: 4/7. (PMID:27040692;PMID:37876076;PMID:36273129)
- Fetal pyelectasis (HP:0010945): Mild pyelectasis is defined as a hypoechoic spherical or elliptical space within the renal pelvis that measures at least 5mm and not more than 10 mm. The measurement is taken on a transverse section through the fetal renal pelvis using the maximum anterior-to-posterior measurement. Evidence: PCS. Frequency: 1/13. Onset: Fetal onset (HP:0011461). (PMID:27040691)
- 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: 1/6. (PMID:27275012;PMID:36273129;PMID:32363625)
- Distal amyotrophy (HP:0003693): Muscular atrophy affecting muscles in the distal portions of the extremities. Evidence: PCS. Frequency: 8/8. (PMID:29283439)
- Limb muscle weakness (HP:0003690): Reduced strength and weakness of the muscles of the arms and legs. Evidence: PCS. Frequency: 10/10. (PMID:32363625;PMID:29283439)
- Motor delay (HP:0001270): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: PCS. Frequency: 34/35. (PMID:27040691;PMID:37876076;PMID:30103036;PMID:27275012;PMID:36273129;PMID:32363625;PMID:29283439;PMID:36522252)
- Brain atrophy (HP:0012444): Partial or complete wasting (loss) of brain tissue that was once present. Evidence: PCS. (PMID:27040692)
- 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: 6/12. (PMID:27040692;PMID:27275012;PMID:36522252)
- 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: PCS. Frequency: 2/14. (PMID:27040691;PMID:36273129)
- Periventricular leukomalacia (HP:0006970): Periventricular leukomalacia is characterized by diffuse injury of deep cerebral white matter, accompanied in its most severe form by focal necrosis. The neuropathologic hallmarks of PVL are microglial activation and focal and diffuse periventricular depletion of premyelinating oligodendroglia. Evidence: PCS. Frequency: 2/15. (PMID:27040691;PMID:37876076;PMID:36273129)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: PCS. Frequency: 7/7. (PMID:27040692;PMID:32363625)
- 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: 2/6. (PMID:36522252)
- Axial muscle weakness (HP:0003327): Reduced strength of the axial musculature (i.e., of the muscles of the head and neck, spine, and ribs). Evidence: PCS. Frequency: 2/2. (PMID:32363625)
- Gingival overgrowth (HP:0000212): Hyperplasia of the gingiva (that is, a thickening of the soft tissue overlying the alveolar ridge. The degree of thickening ranges from involvement of the interdental papillae alone to gingival overgrowth covering the entire tooth crown. Evidence: PCS. Frequency: 2/5. (PMID:27040692;PMID:37876076;PMID:36273129)
- Cerebellar vermis hypoplasia (HP:0001320): Underdevelopment of the vermis of cerebellum. Evidence: PCS. (PMID:27040692)
- Oligohydramnios (HP:0001562): Diminished amniotic fluid volume in pregnancy. Evidence: PCS. Frequency: 1/11. Onset: Antenatal onset (HP:0030674). (PMID:27040691)
- Limb undergrowth (HP:0009826): Limb shortening because of underdevelopment of one or more bones of the extremities. Evidence: PCS. Frequency: 6/8. (PMID:29283439)
- Polyhydramnios (HP:0001561): The presence of excess amniotic fluid in the uterus during pregnancy. Evidence: PCS. Frequency: 1/6. (PMID:36522252)
- 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: 7/7. (PMID:27040691;PMID:36273129)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: PCS. Frequency: 4/17. (PMID:27040691;PMID:30103036;PMID:32363625)
- 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: 0/11. (PMID:30103036;PMID:32363625;PMID:29283439)
- 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: TAS. (OMIM:616900)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: PCS. Frequency: 11/34. (PMID:27040691;PMID:27040692;PMID:32363625;PMID:29283439;PMID:36522252)
- Open mouth (HP:0000194): A facial appearance characterized by a permanently or nearly permanently opened mouth. Evidence: PCS. Frequency: 4/16. (PMID:27040691;PMID:30103036;PMID:36273129)
- Prominent metopic ridge (HP:0005487): Vertical bony ridge positioned in the midline of the forehead. Evidence: PCS. Frequency: 2/21. (PMID:27040691;PMID:37876076;PMID:36273129;PMID:36522252)
- Areflexia (HP:0001284): Absence of neurologic reflexes such as the knee-jerk reaction. Evidence: PCS. Frequency: 8/8. (PMID:29283439)
- Short neck (HP:0000470): Diminished length of the neck. Evidence: PCS. Frequency: 1/13. (PMID:27040691)
- Respiratory insufficiency (HP:0002093). Evidence: PCS. Frequency: 10/15. (PMID:27040692;PMID:30103036;PMID:29283439)
- EMG: myokymic discharges (HP:0100288): The presence of spontaneous bursts of rapidly firing potentials that recur at regular intervals of 2-10 per second and are unaffected by voluntary effort. This is an electromyographic (EMG) finding. Evidence: PCS. Frequency: 1/2. (PMID:30103036)
- Mildly elevated creatine kinase (HP:0008180). Evidence: PCS. Frequency: 2/2. (PMID:32363625)
- Gastrostomy tube feeding in infancy (HP:0011471): Feeding problem necessitating gastrostomy tube feeding. Evidence: PCS. Frequency: 5/5. (PMID:27040692)
- Broad toe (HP:0001837): Visible increase in width of the non-hallux digit without an increase in the dorso-ventral dimension. Evidence: PCS. Frequency: 1/13. (PMID:27040691)
- 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: PCS. Frequency: 1/5. (PMID:27040692)
- 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: 6/6. (PMID:29283439)
- Decreased fetal movement (HP:0001558): An abnormal reduction in quantity or strength of fetal movements. Evidence: PCS. Frequency: 1/11. Onset: Antenatal onset (HP:0030674). (PMID:27040691)
- Decreased fetal movement (HP:0001558): An abnormal reduction in quantity or strength of fetal movements. Evidence: PCS. Frequency: 1/6. (PMID:36522252)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: PCS. Frequency: 1/6. (PMID:36522252)
- 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: 2/15. (PMID:27040691;PMID:37876076;PMID:36273129)
- Poor speech (HP:0002465). Evidence: PCS. (PMID:27040691)
- 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: 7/21. (PMID:27040691;PMID:37876076;PMID:36273129;PMID:36522252)
- 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: 26/37. (PMID:27040691;PMID:27040692;PMID:30103036;PMID:27275012;PMID:36273129;PMID:29283439;PMID:36522252)
- 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: 14/14. (PMID:29283439;PMID:36522252)
- 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: 35/35. (PMID:27040691;PMID:27040692;PMID:37876076;PMID:30103036;PMID:27275012;PMID:36273129;PMID:32363625;PMID:29283439)
- Severe muscular hypotonia (HP:0006829): A severe degree of muscular hypotonia characterized by markedly reduced muscle tone. Evidence: PCS. Frequency: 5/5. (PMID:27040692)
- Reduced brain N-acetyl aspartate level by MRS (HP:0012708): A decrease in the level of N-acetyl aspartate in the brain identified by magnetic resonance spectroscopy (MRS). Evidence: PCS. Frequency: 3/3. (PMID:27040692)
- Acromelia (HP:0010884): Shortening of the extremities affecting primarily the distal parts of the limbs (hands and feet) in relation to the other segments of the limbs. Evidence: PCS. Frequency: 8/8. (PMID:29283439)
- Coarse facial features (HP:0000280): Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues. Evidence: PCS. Frequency: 17/34. (PMID:27040691;PMID:27040692;PMID:37876076;PMID:36273129;PMID:29283439;PMID:36522252)
- Hypertelorism (HP:0000316): Interpupillary distance more than 2 SD above the mean (alternatively, the appearance of an increased interpupillary distance or widely spaced eyes). Evidence: PCS. Frequency: 1/2. (PMID:37876076;PMID:36273129)
- Single transverse palmar crease (HP:0000954): The distal and proximal transverse palmar creases are merged into a single transverse palmar crease. Evidence: PCS. Frequency: 3/3. (PMID:27275012)
- Macroglossia (HP:0000158): Increased length and width of the tongue. Evidence: PCS. Frequency: 14/34. (PMID:27040691;PMID:27040692;PMID:37876076;PMID:36273129;PMID:29283439;PMID:36522252)
- Hirsutism (HP:0001007): Abnormally increased hair growth referring to a male pattern of body hair (androgenic hair). Evidence: PCS. Frequency: 4/22. (PMID:27040691;PMID:36273129;PMID:32363625;PMID:36522252)
- EMG: chronic denervation signs (HP:0003444): Evidence of chronic denervation on electromyography. Evidence: PCS. Frequency: 5/9. (PMID:29283439;PMID:36522252)
- Hyporeflexia (HP:0001265): Reduction of neurologic reflexes such as the knee-jerk reaction. Evidence: PCS. Frequency: 20/25. (PMID:27040691;PMID:27040692;PMID:37876076;PMID:36273129;PMID:32363625;PMID:36522252)
- Delayed skeletal maturation (HP:0002750): A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body. Evidence: PCS. Frequency: 2/2. (PMID:27040691)
- Hypoplasia of the corpus callosum (HP:0002079): Underdevelopment of the corpus callosum. Evidence: PCS. (PMID:27040691)
- 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: 3/3. (PMID:37876076;PMID:36522252)
- 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: 32/32. (PMID:27040691;PMID:27040692;PMID:37876076;PMID:30103036;PMID:27275012;PMID:32363625;PMID:36522252)
- Decreased compound muscle action potential amplitude (HP:0033383): Reduced level of the compound muscle action potential (CMAP), which is recorded following electrical stimulation of a nerve from surface electrodes overlying a muscle supplied by that nerve. Evidence: PCS. Frequency: 3/7. (PMID:29283439;PMID:36522252)
- Right aortic arch (HP:0012020): Aorta descends on right instead of on the left. Evidence: PCS. Frequency: 1/5. (PMID:27040692)
- Esotropia (HP:0000565): A form of strabismus with one or both eyes turned inward ('crossed') to a relatively severe degree, usually defined as 10 diopters or more. Evidence: PCS. Frequency: 1/5. (PMID:27040692)
- Increased variability in muscle fiber diameter (HP:0003557): An abnormally high degree of muscle fiber size variation. This phenotypic feature can be observed upon muscle biopsy. Evidence: PCS. Frequency: 2/2. (PMID:32363625)
- Global brain atrophy (HP:0002283): Unlocalized atrophy of the brain with decreased total brain matter volume and increased ventricular size. Evidence: PCS. Frequency: 8/21. (PMID:27040691;PMID:36273129;PMID:32363625;PMID:29283439)
- Turricephaly (HP:0000262): Tall head relative to width and length. Evidence: PCS. Frequency: 1/6. (PMID:36522252)
- 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: 1/1. (PMID:32363625)
- Osteoporosis (HP:0000939): Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD). Evidence: PCS. Frequency: 9/12. (PMID:27040692;PMID:29283439)
- Bulbous nose (HP:0000414): Increased volume and globular shape of the anteroinferior aspect of the nose. Evidence: PCS. Frequency: 3/15. (PMID:27040691;PMID:37876076;PMID:36273129)
- Broad finger (HP:0001500): Increased width of a non-thumb digit of the hand. Evidence: PCS. Frequency: 1/13. (PMID:27040691)
- 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: PCS. Frequency: 6/17. (PMID:27040691;PMID:30103036;PMID:36273129;PMID:32363625)
- Intermittent hypothermia (HP:0005964): Episodes of reduced body temperature. Evidence: PCS. Frequency: 6/8. (PMID:29283439)
- 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: PCS. Frequency: 1/6. (PMID:36522252)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: TAS. (OMIM:616900)
- Wide nasal bridge (HP:0000431): Increased breadth of the nasal bridge (and with it, the nasal root). Evidence: PCS. Frequency: 1/15. (PMID:27040691;PMID:37876076;PMID:36273129)
- Extra-axial cerebrospinal fluid accumulation (HP:0012510): An increased amount of cerebrospinal fluid (CSF) in the subarachnoid space. Evidence: PCS. Frequency: 5/5. (PMID:27040692)
- Prominent nasal bridge (HP:0000426): Anterior positioning of the nasal root in comparison to the usual positioning for age. Evidence: PCS. Frequency: 5/7. (PMID:27040692;PMID:37876076;PMID:36273129)
- Hypothyroidism (HP:0000821): Deficiency of thyroid hormone. Evidence: PCS. Frequency: 3/7. (PMID:29283439)
- Bilateral tonic-clonic seizure with focal onset (HP:0007334): A bilateral tonic-clonic seizure with focal onset is a focal-onset seizure which progresses into a bilateral tonic-clonic phase. Evidence: PCS. Frequency: 2/2. (PMID:32363625)
- Synophrys (HP:0000664): Meeting of the medial eyebrows in the midline. Evidence: PCS. Frequency: 1/15. (PMID:27040691;PMID:37876076;PMID:36273129)
- Cryptorchidism (HP:0000028): Testis in inguinal canal. That is, absence of one or both testes from the scrotum owing to failure of the testis or testes to descend through the inguinal canal to the scrotum. Evidence: PCS. Frequency: 3/5. (PMID:36273129;PMID:36522252)
- Mandibular prognathia (HP:0000303): Abnormal prominence of the chin related to increased length of the mandible. Evidence: PCS. Frequency: 1/14. (PMID:27040691;PMID:36273129)