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Inclusion Criteria
- De novo translocation where extreme phenotype present - Familial balanced translation that co-segregates with disease - Routine investigations pertaining to the presenting phenotype have been carried out with normal results - Genome-wide copy number variant testing has demonstrated no significant genomic rearrangement at the break points
Exclusion Criteria
- Genome-wide copy number variant analysis abnormal and clearly pathogenic
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: - Genome-wide copy number variant analysis (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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Small for gestational age
Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age.
Large for gestational age
The term large for gestational age applies to babies whose birth weight lies above the 90th percentile for that gestational age. Comment: Fetal macrosomia has been defined in several different ways, including birth weight of 4000-4500 g (8 lb 13 oz to 9 lb 15 oz) or greater than 90% for gestational age after correcting for neonatal sex and ethnicity. Based on these definitions, macrosomia affects 1-10% of all pregnancies. A diagnosis of fetal macrosomia can be made only by measuring birth weight after delivery; therefore, the condition is confirmed only retrospectively, ie, after delivery of the neonate.
Failure to thrive
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Comment: Although there is no clear consensus on the exact definition of FTT, it is usually diagnoses in a child growing below the 3rd percentile or in a child whose decreased growth has cross two major growth percentiles (for example, from above the 75th percentile to below the 25th percentile).
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).
Tall stature
A height above that which is expected according to age and gender 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.
Macrocephaly
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium. Comment: Macrocephaly can be due to hydrocephalus (increased CFSF), megalencephaly (increased brain volume) or thickening of the skull. 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 above the normal standard the head circumference is if an accurate assessment of this can be made. Macrocephaly is an absolute term. The term relative macrocephaly can be used when the head size centile exceeds the centile for height, for example, head size at the 75th centile with height at the 5th centile for age and sex.
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.
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).
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.
Hyperpigmented streaks
Hypermelanotic macule
A hyperpigmented circumscribed area of change in normal skin color without elevation or depression of any size.
Macular hypopigmented whorls, streaks, and patches
Hypopigmentation of the skin
A reduction of skin color related to a decrease in melanin production and deposition.
Cutaneous photosensitivity
An increased sensitivity of the skin to light. Photosensitivity may result in a rash upon exposure to the sun (which is known as photodermatosis). Photosensitivity can be diagnosed by phototests in which light is shone on small areas of skin.
Abnormality of the cardiovascular system
Any abnormality of the cardiovascular system. Comment: The cardiovascular system consists of the heart, vasculature, and the lymphatic system.
Abnormality of the musculature
Abnormality originating in one or more muscles, i.e., of the set of muscles of body.
Abnormality of the gastrointestinal tract
An abnormality of the gastrointestinal tract.
Abnormality of the liver
An abnormality of the liver.
Abnormality of the respiratory system
An abnormality of the respiratory system, which include the airways, lungs, and the respiratory muscles.
Abnormality of the endocrine system
Ab abnormality of the endocrine system. Comment: The endocrine system is composed of glands that secrete hormones directly into the bloodstream and includes the following glands: thyroid, parathyroids, adrenals, pancreas, gonads (testicles and ovaries), and pituitary. Many other organs, such as the kidney, liver, and heart, have secondary endocrine functions.
Abnormality of metabolism/homeostasis
Abnormality of blood and blood-forming tissues
An abnormality of the hematopoietic system. Comment: The hematopoietic system comprises the organs that are involved in the production of blood, primarily the bone marrow, spleen, tonsils, and lymph nodes.
Abnormality of the immune system
An abnormality of the immune system. Comment: The immune system is composed of organs and interdependent cell types that collectively protect the body from infections and from the growth of tumor cells. The organs of the immune system comprise the bone marrow, the spleen, the thymus,the lymph nodes, and the cell types comprise B cells, T cells, natural killer cells, granulocytes,dendritic cells, and macrophages.
Abnormality of the skeletal system
An abnormality of the skeletal system.
Abnormality of the genitourinary system
The presence of any abnormality of the genitourinary system.
Abnormality of prenatal development or birth
An abnormality of the fetus or the birth of the fetus, excluding structural abnormalities. Comment: Because of the close link between prenatal developmental abnormalities and abnormalities of the birth process, a single term is chosen to subsume both classes of abnormality.
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- APGAR score
- Facial features most in keeping with an OMIM disease
- 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.