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Inclusion Criteria
- Multiple congenital bilateral joint contractures - EMG/NCV completed - Creatinine kinase measured - MRI brain if developmentally delayed or otherwise clinically indicated - TORCH screen if developmentally delayed and less than 6 months old - Maternal anti-acetylcholine receptor antibodies - Consideration of skeletal survey to exclude skeletal dysplasia
Exclusion Criteria
- Isolated talipes/clubfoot - Oligohydramnios - Major structural CNS abnormalities likely to be causative of phenotype - Confident clinical diagnosis of amyoplasia
Prior Genetic Testing
- Results should have been reviewed for all genetic tests undertaken, including disease-relevant genes in exome sequencing data. The patient is not eligible if they have a molecular diagnosis for their condition. - Genetic testing should continue according to routine local practice for this phenotype regardless of recruitment to the project; results of these tests must be submitted via the ‘Genetic investigations’ section of the data capture tool to allow comparison of WGS with current standard testing. PLEASE NOTE: The sensitivity of WGS compared to current diagnostic genetic testing has not yet been established. It is therefore important that tests which are clinically indicated under local standard practice continue to be carried out.
Genes
Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice: - If associated with other abnormalities, genome-wide copy number variation testing (e.g. aCGH, SNP array or other genomic microarray)
Closing Statement
These requirements will be kept under continual review during the main programme and may be subject to change.
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Arthrogryposis multiplex congenita
A non-progressive finding characterized by multiple joint contractures found throughout the body at birth. Comment: Arthrogryposis multiplex congenita (AMC) is related to fetal akinesia owing to fetal neurogenic, muscle, or connective tissue disorders or occasionally to maternal conditions. AMC can be associated with polyhydramnios, pulmonary hypoplasia, micrognathia, ocular hypertelorism, and short umbilical cord. AMC is a feature of a heterogeneous group of disorders, some of which have the phrase 'arthrogryposis multiplex congenita' as a part of their name (for instance, Arthrogryposis multiplex congenita, distal type 1 or AMCD1). This term refers to the finding of multiple joint contractures found throughout the body at birth rather than to the disease entities of which this is a clinical feature.
Contractures of the joints of the upper limbs
Contractures of the joints of the lower limbs
Elbow flexion contracture
A chronic loss of elbow joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevent normal movement of the joints of the elbow.
Hip contracture
Permanent fixation of the hip in primary positions, with limited passive or active motion at the hip joint.
Knee flexion contracture
A bent (flexed) knee joint that cannot be straightened actively or passively.
Distal arthrogryposis
A form of arthrogryposis primarily affecting the hands and the feet.
Camptodactyly of finger
The distal interphalangeal joint and/or the proximal interphalangeal joint of the fingers cannot be extended to 180 degrees by either active or passive extension. Comment: Note that some restrict the use of the term to inability to extend the proximal interphalangeal joint of the fifth finger. We do not restrict the term in this way. This term should not be used if the patient has Clenched hand. A similar effect can be created by radial angulation within the distal phalanx with thickening of the epiphysis, which is called Kirner deformity or dystelephalangy. The affected digits should be specified.
Ankle contracture
A chronic loss of ankle joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevent normal movement of the joints of the ankle.
Skeletal muscle atrophy
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
Abnormality of muscle morphology
A structural abnormality of a skeletal muscle.
Limb muscle weakness
Reduced strength and weakness of the muscles of the arms and legs.
Axial muscle weakness
Reduced strength of the axial musculature (i.e., of the muscles of the head and neck, spine, and ribs).
Fatigable weakness
A type of weakness that occurs after a muscle group is used and lessens if the muscle group has some rest. That is, there is diminution of strength with repetitive muscle actions. Comment: This type of weakness is pathognomonic for an abnormality of the neuromuscular junction such as myasthenia gravis. A characteristic form of muscular weakness that worsens after use of affected muscles. Myasthenia is caused by failure of neuromuscular transmission, which results from the binding of autoantibodies to proteins involved in signaling at the neuromuscular junction, including especially the nicotinic acetyl choline receptor (AChR) or, less frequently, a muscle-specific tyrosine kinase involved in AChR clustering.
Decreased fetal movement
An abnormal reduction in quantity or strength of fetal movements.
Polyhydramnios
The presence of excess amniotic fluid in the uterus during pregnancy. Comment: Polyhydramnios is diagnosed if the deepest vertical pool of amniotic fluid is more than 8 cm or amniotic fluid index is more than 95th percentile for the corresponding gestational age.
Oligohydramnios
Diminished amniotic fluid volume in pregnancy. Comment: Oligohydramnios is the opposite of polyhydramnios. In normal pregnancy the amniotic fluid volume increases by about 10 ml/day until the 34th, after which it slowly diminishes. A normal amniotic fluid volume at term is about 500-2,000 ml. Oligohydramnios is defined as an AFI (amniotic fluid index) less than 5 cm or smallest vertical pocket of fluid less than 2 cm.
Neonatal hypotonia
Muscular hypotonia (abnormally low muscle tone) manifesting in the neonatal period.
Inability to walk
Incapability to ambulate.
Intellectual disability
Subnormal intellectual functioning which originates during the developmental period. Intellectual disability, previously referred to as mental retardation, has been defined as an IQ score below 70. Comment: This term should be used for children at least five years old. For younger children, consider the term Global developmental delay (HP:0001263).
Short stature
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).
Microcephaly
Occipito-frontal (head) circumference (OFC) less than -3 standard deviations compared to appropriate, age matched, normal standards (Ross JJ, Frias JL 1977, PMID:9683597). Alternatively, decreased size of the cranium. Comment: Head circumference is measured from just above the glabella (the most prominent point on the frontal bone above the root of the nose) to the most posterior prominent point of the occipital bone using a tape measure. Some standard charts are organized by centiles [Hall et al. [2007]], others by standard deviations [Farkas, [1981]]. It is important to add an indication of how far below the normal standard the head circumference is if an accurate assessment of this can be made. Microcephaly is an absolute term. The term relative microcephaly can be used when the head size centile is less than the centile for height, for example, head size at the 3rd centile with height at the 75% for age and sex. On prenatal ultrasound, microcephaly is diagnosed if the head circumference or the biparietal diameter is more than three standard deviations below the mean.
Abnormal facial shape
An abnormal morphology (form) of the face or its components. Comment: This term now covers many of the historical inexact descriptions such as Bird-like facies that probably should be avoided in modern genetics. This portion of the Ontology should be revised.
Global developmental delay
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. Comment: Developmental retardation is any significant lag in development in the any or all of the physical, cognitive, behavioral, emotional, or social spheres. Note that the term intellectual disability (mental retardation) refers to not merely a delay in development but rather a permanent limitation. Note that the term 'psychomotor retardation' is also used in some contexts to refer to a slowing of thought and physical movements as a result of major depression or intoxication.
Skeletal dysplasia
A general term describing features characterized by abnormal development of bones and connective tissues. Comment: The word skeletal dysplasia is most often used to describe a group of over 380 inherited conditions that involve abnormal development of bones and connective tissues. However, the word can also be used to describe the presence of a congenital defects of bones or connective tissues that are found in one or more of the diseases, especially on prenatal ultrasound, i.e., a situation in which it is often not yet possible to make an exact etiological diagnosis. This is the sense of the phrase we use in the HPO. It is, however, preferable to annotate the observed abnormalities.
Scoliosis
The presence of an abnormal lateral curvature of the spine.
Blepharophimosis
A fixed reduction in the vertical distance between the upper and lower eyelids with short palpebral fissures. Comment: When the palpebral fissures are severely shortened, they cannot be widely separated, actively or passively.
Cataract
A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule. Comment: Note that some ophthalmologists call any opacity in the lens a cataract, while others restrict the term to lens opacities that impair vision. We use the term to refer to the first meaning (any lens opacity).
Cleft palate
Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate). Comment: Cleft palate is a developmental defect that occurs between the 7th and 12th week of pregnancy. Normally, the palatine processes fuse during this time to form the soft and hard palate. A failure of fusion results in a cleft palate. The clinical spectrum ranges from bifid uvula, to (incomplete or complete) cleft of the soft palate, up to (complete or incomplete) cleft of both the soft and hard palate.
Respiratory insufficiency
Failure to adequately provide oxygen to cells of the body and to remove excess carbon dioxide.
Arrhythmia
Any cardiac rhythm other than the normal sinus rhythm. Such a rhythm may be either of sinus or ectopic origin and either regular or irregular. An arrhythmia may be due to a disturbance in impulse formation or conduction or both.
Cardiomyopathy
A myocardial disorder in which the heart muscle is structurally and functionally abnormal, in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease sufficient to cause the observed myocardial abnormality.
Abnormal heart morphology
Any structural anomaly of the heart.
Seizures
Seizures are an intermittent abnormality of the central nervous system due to a sudden, excessive, disorderly discharge of cerebral neurons and characterized clinically by some combination of disturbance of sensation, loss of consciousness, impairment of psychic function, or convulsive movements. The term epilepsy is used to describe chronic, recurrent seizures. Comment: The term epilepsy is not used to describe recurrent febrile seizures. Epilepsy presumably reflects an abnormally reduced seizure threshold.
Abnormality of the cerebrum
An abnormality of the telencephalon, which is also known as the cerebrum.
Abnormality of the cerebral white matter
An abnormality of the cerebral white matter. Comment: This finding can be demonstrated by magnetic resonance imaging, especially with t2 signalling. The cerebral white matter is the region of the central nervous system that consists mostly of glial cells and myelinated axons that interconnect the various regions of the cerebrum and the lower brain centers. It is located in the subcortex.
Abnormality of the cerebellum
An abnormality of the cerebellum.
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- Forced vital capacity
- Other enzymes
- General Biopsy
General investigation report to capture biopsies. Inherits all the elements in the abstract Biopsy class and the abstract Investigation Class.
- General Imaging Diagnostics
General imaging diagnostics report to capture reports that aren't included in the specific subclasses. Inherits all the elements in the abstract Imaging Diagnostics class and the abstract Investigation Class.
- General Non-imaging Diagnostics