Phenotypes associated with the disease immunoskeletal dysplasia with neurodevelopmental abnormalities (OMIM:617425):
- Pear-shaped vertebrae (HP:0004566): Bulbous appearance of the anterior vertebral bodies, such that the vertebral bodies have the greatest vertical height anteriorly as well as bulbous anterior superior-inferior contours. Evidence: PCS. Frequency: 1/3. (PMID:28148688)
- Anal atresia (HP:0002023): Congenital absence of the anus, i.e., the opening at the bottom end of the intestinal tract. Evidence: PCS. Frequency: 3/12. (OMIM:617425;PMID:28148688)
- Chalazion (HP:0010605): A chronic epithelioid cell granulomatous inflammation of the meibomian gland caused by inflammation of a blocked meibomian gland. A chalazion or meibomian cyst appears as a painless tuberous swelling in the upper lid without loss of eyelashes. Evidence: PCS. Frequency: 1/3. (PMID:28148688)
- 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: 4/6. (PMID:28132690)
- 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: 3/3. (PMID:28331220;PMID:28148688)
- 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: 1/1. (PMID:28148688)
- Short nose (HP:0003196): Distance from nasion to subnasale more than two standard deviations below the mean, or alternatively, an apparently decreased length from the nasal root to the nasal tip. Evidence: PCS. Frequency: 1/1. (PMID:28331220)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 4/11. (PMID:28132690;PMID:28331220)
- 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: 6/7. (PMID:28132690)
- Metaphyseal dysplasia (HP:0100255): The presence of dysplastic regions in metaphyseal regions. Evidence: PCS. Frequency: 2/9. (PMID:28132690)
- Abnormally low T cell receptor excision circle level (HP:0031545): Reduced level of T cell receptor excision circle (TRECs) as measured by the TREC assay. Late in maturation, 70% of thymocytes that will ultimately express alpha/beta-T cell receptors form a circular DNA TREC from the excised TCRdelta gene that lies within the TCRalpha genetic locus. The circles are stable but do not increase following cell division and, therefore, become diluted as T cells proliferate. A quantitative polymerase chain reaction (PCR) reaction across the joint of the circular DNA provides the TREC copy number, a marker of newly-formed, antigenically-naïve thymic emigrant T cells. Evidence: PCS. Frequency: 3/3. (PMID:28148688)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: PCS. Frequency: 1/3. (PMID:28148688)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 1/9. (PMID:28132690)
- Young adult onset (HP:0011462): Onset of disease at the age of between 16 and 40 years. Evidence: PCS. Frequency: 2/9. (PMID:28132690)
- Lumbar hyperlordosis (HP:0002938): An abnormal accentuation of the inward curvature of the spine in the lumbar region. Evidence: PCS. Frequency: 1/3. (PMID:28148688)
- 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: 1/7. (PMID:28132690)
- Sepsis (HP:0100806): Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Evidence: PCS. Frequency: 1/1. (PMID:28148688)
- Single transverse palmar crease (HP:0000954): The distal and proximal transverse palmar creases are merged into a single transverse palmar crease. Evidence: PCS. Frequency: 5/7. (PMID:28132690)
- Decreased total lymphocyte count (HP:0001888): A reduced number of lymphocytes in the blood. Evidence: PCS. Frequency: 1/9. (PMID:28132690)
- 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: 1/3. (PMID:28148688)
- Hepatic cysts (HP:0001407). Evidence: PCS. Frequency: 6/14. (PMID:28132690;PMID:28331220;PMID:28148688)
- Death in infancy (HP:0001522): Death within the first 24 months of life. Evidence: PCS. Frequency: 3/9. (PMID:28132690)
- Epiphyseal dysplasia (HP:0002656). Evidence: PCS. (PMID:28132690)
- 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: 3/6. (PMID:28132690)
- Simple ear (HP:0020206): The pinna has fewer folds and grooves than usual. Evidence: PCS. Frequency: 1/3. (PMID:28148688)
- Decreased circulating IgG concentration (HP:0004315): An abnormally decreased level of immunoglobulin G (IgG) in blood. Evidence: PCS. Frequency: 1/1. (PMID:28331220)
- Neonatal onset (HP:0003623): Onset of signs or symptoms of disease within the first 28 days of life. Evidence: PCS. (PMID:28132690)
- Kyphoscoliosis (HP:0002751): An abnormal curvature of the spine in both a coronal (lateral) and sagittal (back-to-front) plane. Evidence: PCS. Frequency: 1/9. (PMID:28132690)
- Progressive microcephaly (HP:0000253): Progressive microcephaly is diagnosed when the head circumference falls progressively behind age- and gender-dependent norms. Evidence: PCS. Frequency: 1/9. (PMID:28132690)
- Hip dysplasia (HP:0001385): The presence of developmental dysplasia of the hip. Evidence: PCS. Frequency: 1/3. (PMID:28148688)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 3/4. (PMID:28132690;PMID:28331220)
- Hypertriglyceridemia (HP:0002155): An abnormal increase in the level of triglycerides in the blood. Evidence: PCS. Frequency: 1/3. (PMID:28148688)
- Coxa valga (HP:0002673): Coxa valga is a deformity of the hip in which the angle between the femoral shaft and the femoral neck is increased compared to age-adjusted values (about 150 degrees in newborns gradually reducing to 120-130 degrees in adults). Evidence: PCS. Frequency: 3/3. (PMID:28132690)
- Laryngotracheal stenosis (HP:0004894). Evidence: PCS. Frequency: 1/3. (PMID:28148688)
- Short chin (HP:0000331): Decreased vertical distance from the vermilion border of the lower lip to the inferior-most point of the chin. Evidence: PCS. Frequency: 1/3. (PMID:28148688)
- Full cheeks (HP:0000293): Increased prominence or roundness of soft tissues between zygomata and mandible. Evidence: PCS. Frequency: 1/7. (PMID:28132690)
- Generalized-onset seizure (HP:0002197): A generalized-onset seizure is a type of seizure originating at some point within, and rapidly engaging, bilaterally distributed networks. The networks may include cortical and subcortical structures but not necessarily the entire cortex. Evidence: PCS. Frequency: 1/3. (PMID:28148688)
- 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: 6/6. (PMID:28132690;PMID:28331220;PMID:28148688)
- Dislocated radial head (HP:0003083): A dislocation of the head of the radius from its socket in the elbow joint. Evidence: PCS. Frequency: 4/9. (PMID:28132690)
- Platyspondyly (HP:0000926): A flattened vertebral body shape with reduced distance between the vertebral endplates. Evidence: PCS. Frequency: 11/11. (PMID:28132690;PMID:28331220;PMID:28148688)
- 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: 3/12. (PMID:28132690;PMID:28148688)
- Prominent nose (HP:0000448): Distance between subnasale and pronasale more than two standard deviations above the mean, or alternatively, an apparently increased anterior protrusion of the nasal tip. Evidence: PCS. Frequency: 1/7. (PMID:28132690)
- 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. Frequency: 20/20. (PMID:28132690;PMID:28148688)
- Erythroderma (HP:0001019): An inflammatory exfoliative dermatosis involving nearly all of the surface of the skin. Erythroderma develops suddenly. A patchy erythema may generalize and spread to affect most of the skin. Scaling may appear in 2-6 days and be accompanied by hot, red, dry skin, malaise, and fever. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:617425)
- Thoracolumbar kyphosis (HP:0005619): Hyperconvexity of the thoracolumbar spine producing a rounded or humped appearance. Evidence: PCS. Frequency: 5/11. (PMID:28132690;PMID:28331220;PMID:28148688)
- Cervical spinal canal stenosis (HP:0008445): An abnormal narrowing of the cervical spinal canal. Evidence: PCS. Frequency: 5/5. (PMID:28331220;PMID:28148688)
- Sacral dimple (HP:0000960): A cutaneous indentation resulting from tethering of the skin to underlying structures (bone) of the intergluteal cleft. Evidence: PCS. Frequency: 1/1. (PMID:28331220)
- Thoracic scoliosis (HP:0002943). Evidence: PCS. Frequency: 1/3. (PMID:28148688)
- Delayed ossification of carpal bones (HP:0001216): Ossification of carpal bones occurs later than age-adjusted norms. Evidence: PCS. Frequency: 5/9. (PMID:28132690)
- Scaphocephaly (HP:0030799): Scaphocephaly is a subtype of dolichocephaly where the anterior and posterior aspects of the cranial vault are pointed (boat-shaped). Scaphocephaly is caused by a precocious fusion of sagittal suture without other associated synostosis. Evidence: PCS. Frequency: 1/3. (PMID:28148688)
- Clonus (HP:0002169): A series of rhythmic and involuntary muscle contractions (at a frequency of about 5 to 7 Hz) that occur in response to an abruptly applied and sustained stretch. Evidence: PCS. Frequency: 1/3. (PMID:28148688)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 14/15. (PMID:28132690;PMID:28331220;PMID:28148688)
- Metaphyseal widening (HP:0003016): Abnormal widening of the metaphyseal regions of long bones. Evidence: PCS. Frequency: 1/1. (PMID:28331220)
- 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: 2/6. (PMID:28132690;PMID:28148688)
- 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: 1/2. (PMID:28331220)
- Brachydactyly (HP:0001156): Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here. Evidence: PCS. Frequency: 9/13. (PMID:28132690;PMID:28331220;PMID:28148688)
- Disproportionate short stature (HP:0003498): A kind of short stature in which different regions of the body are shortened to differing extents. Evidence: PCS. Frequency: 6/9. (PMID:28132690)
- Narrow greater sciatic notch (HP:0003375): A narrowing of the sacrosciatic notch, i.e., the deep indentation in the posterior border of the hip bone at the point of union of the ilium and ischium. Evidence: TAS. (OMIM:617425)
- Severe T-cell immunodeficiency (HP:0005352): A primary immune deficiency that is characterized by defects or deficiencies of T-lymphocytes that causes specific susceptibility to intracellular micro-organisms. Evidence: PCS. Frequency: 2/12. (PMID:28132690;PMID:28148688)
- Motor delay (HP:0001270): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: PCS. (PMID:28132690)
- Trident hand (HP:0004060): A hand in which the fingers are of nearly equal length and deflected at the first interphalangeal joint, so as to give a forklike shape consisting of separation of the first and second as well as the third and fourth digits. Evidence: PCS. Frequency: 1/1. (PMID:28331220)
- Hypoplasia of the capital femoral epiphysis (HP:0003090): Underdevelopment of the proximal epiphysis of the femur. Evidence: PCS. Frequency: 5/5. (PMID:28132690)
- Broad ischia (HP:0100865): Increased width of the ischium, which forms the lower and back part of the hip bone. Evidence: PCS. Frequency: 1/1. (PMID:28331220)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 2/3. (PMID:28148688)
- Recurrent infections (HP:0002719): Increased susceptibility to infections as manifested by repeated bouts of infection. Evidence: PCS. Frequency: 4/12. (PMID:28132690;PMID:28148688)
- Lower limb muscle weakness (HP:0007340): Weakness of the muscles of the legs. Evidence: PCS. Frequency: 1/1. (PMID:28331220)
- Disproportionate short-limb short stature (HP:0008873): A type of disproportionate short stature characterized by a short limbs but an average-sized trunk. Evidence: PCS. Frequency: 4/5. (PMID:28132690;PMID:28148688)
- Fetal distress (HP:0025116): An intrauterine state characterized by suboptimal values in the fetal heart rate, oxygenation of fetal blood, or other parameters indicative of compromise of the fetus. Signs of fetal distress include repetitive variable decelerations, fetal tachycardia or bradycardia, late decelerations, or low biophysical profile. Evidence: PCS. Frequency: 2/3. (PMID:28148688)
- Recurrent pneumonia (HP:0006532): An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia. Evidence: PCS. Frequency: 1/2. (PMID:28331220)
- Broad nasal tip (HP:0000455): Increase in width of the nasal tip. Evidence: PCS. Frequency: 3/7. (PMID:28132690)
- Wide intermamillary distance (HP:0006610): A larger than usual distance between the left and right nipple. Evidence: PCS. Frequency: 1/3. (PMID:28148688)
- Blepharitis (HP:0000498): Inflammation of the eyelids. Evidence: PCS. Frequency: 1/3. (PMID:28148688)
- Cloverleaf skull (HP:0002676): Trilobar skull configuration when viewed from the front or behind. Evidence: PCS. Frequency: 1/3. (PMID:28148688)
- Hyperreflexia (HP:0001347): Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles. Evidence: PCS. Frequency: 1/1. (PMID:28148688)
- Axial hypotonia (HP:0008936): Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk. Evidence: PCS. Frequency: 3/9. (PMID:28132690)
- Decreased circulating IgM concentration (HP:0002850): An abnormally decreased level of immunoglobulin M (IgM) in blood. Evidence: PCS. Frequency: 1/1. (PMID:28331220)
- Opisthotonus (HP:0002179): Opisthotonus is defined as a dramatic abnormal posture due to spastic contraction of the extensor muscles of the neck, trunk, and lower extremities that produces a severe backward arching from neck to heel. In most cases, the trunk is elevated off the ground by a few inches. It is usually sudden in onset and can be sustained or repetitive. It can be considered a variant of decerebrate posturing involving a hyperextension of the neck, back, and limbs. Evidence: PCS. Frequency: 1/3. (PMID:28148688)
- Craniosynostosis (HP:0001363): Craniosynostosis refers to the premature closure of the cranial sutures. Primary craniosynostosis refers to the closure of one or more sutures due to abnormalities in skull development, and secondary craniosynostosis results from failure of brain growth. Evidence: PCS. Frequency: 1/3. (PMID:28148688)
- Decreased circulating immunoglobulin concentration (HP:0004313): An abnormally decreased level of immunoglobulin in blood. Evidence: PCS. (PMID:28132690)
- Increased total eosinophil count (HP:0001880): Increased count of eosinophils in the blood. Evidence: PCS. Frequency: 3/9. (PMID:28132690)
- Juvenile onset (HP:0003621): Onset of signs or symptoms of disease between the age of 5 and 15 years. Evidence: PCS. Frequency: 3/9. (PMID:28132690)
- Limb undergrowth (HP:0009826): Limb shortening because of underdevelopment of one or more bones of the extremities. Evidence: PCS. Frequency: 6/10. (PMID:28132690;PMID:28331220;PMID:28148688)
- Polyhydramnios (HP:0001561): The presence of excess amniotic fluid in the uterus during pregnancy. Evidence: PCS. Frequency: 1/1. (PMID:28331220)
- Severe combined immunodeficiency (HP:0004430): A type of primary immune deficiency that is characterized by a more severe defect in both the T- and B-lymphocyte systems. Evidence: PCS. Frequency: 7/12. (PMID:28132690;PMID:28148688)
- Spinal cord compression (HP:0002176): External mechanical compression of the spinal cord. Evidence: PCS. Frequency: 4/4. (PMID:28331220;PMID:28148688)
- Increased intervertebral space (HP:0030320): An increase in the vertical distance between adjacent vertebral bodies, observed as an increase in the intervertebral disk space. Evidence: PCS. Frequency: 3/3. (PMID:28148688)
- Multiple renal cysts (HP:0005562): The presence of many cysts in the kidney. Evidence: PCS. Frequency: 1/2. (PMID:28132690)
- Depressed nasal bridge (HP:0005280): Posterior positioning of the nasal root in relation to the overall facial profile for age. Evidence: PCS. Frequency: 11/12. (PMID:28132690;PMID:28331220)
- Cervical instability (HP:0008462). Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:617425)
- Trident acetabulum (HP:0034374): Abnormal appearance of the acetabulum characterized by spurs at the medial and lateral acetabular margin and in the center of the acetabulum, giving rise to shape resembling a three-pronged spear sadi to resemble a trident. Evidence: PCS. Frequency: 3/3. (PMID:28148688)
- Frontal bossing (HP:0002007): Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline. Evidence: PCS. Frequency: 2/2. (PMID:28331220)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: PCS. Frequency: 4/5. (PMID:28331220;PMID:28148688)