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Inclusion Criteria
- unexplained rod-cone dystrophy/ retinal dystrophy OR - at least two of the major diagnostic features associated with Bardet-Biedl syndrome: - Obesity - Polydacyly - Rod-cone dystrophy/ retinal dystrophy/ retinitis pigmentosa - Hypogenitalism - Renal dysplasia
Exclusion Criteria
- non-syndromic retinitis pigmentosa without features suggestive of rod-cone dystrophy/ cone-rod dystrophy - existing molecular confirmation of a diagnosis of Bardet-Biedl syndrome or another ciliopathy
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 variation testing (e.g. aCGH, SNP array or other genomic microarray) - ARL6, ALMS1, BBS1, BBS10, BBS12, BBS2, BBS4, BBS5, BBS7, BBS9, MKKS, MKS1 and TTC8
Closing Statement
These requirements will be kept under continual review during the main programme and may be subject to change.
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Obesity
Body weight that is grossly above the acceptable or desirable weight, usually due to accumulation of excess fats in the body. The standards may vary with age, sex, genetic or cultural background. In the body mass index (BMI), a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese.
Neurodevelopmental delay
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).
Behavioral abnormality
An abnormality of mental functioning including various affective, behavioural, cognitive and perceptual abnormalities.
Rod-cone dystrophy
Progressive rod photoreceptor dysfunction and loss that leads to night blindness and loss of peripheral visual field, either as the prevailing problem or occurring at least as severely as cone dysfunction. Occurs most often as retinitis pigmentosa (Hereditary degeneration and atrophy of the retina). Comment: Retinitis pigmentosa is a group of hereditary diseases of the eye. However, the term retinitis pigmentosa has also been used to describe the retinal findings characteristic of these diseases but also seen on other diseases such as Usher syndrome. It is preferable to describe the findings precisely if possible, but this term is kept for convenience.
Retinal dystrophy
Optic atrophy
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy. Comment: The diagnosis of optic atrophy is made when the optic disc loses its normal orange-pink color. Optic atrophy is an end stage that arises from myriad causes of optic nerve damage anywhere along the path from the retina to the lateral geniculate. Some of the most common etiologies are advanced glaucoma, optic neuritis, arteritic or non-arteritic ischaemic optic neuropathy or a compressive lesion.
Astigmatism
Astigmatism describes a refractive error characterized by a difference in the horizontal and vertical curvature of the cornea. Comment: The irregular curvature associated with astigmatism means that the optical system is not symmetric about the optical axis. Most commonly the cornea is affected such that the refractive power in one meridian is less than that of the perpendicular axis. Astigmatism of significant degree causes blurry vision.
Strabismus
Strabismus (also known as squint) is a condition in which the eyes are not properly aligned with each other.
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).
Brachydactyly syndrome
Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used to describe a series of Mendelian diseases characterized by distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here, however, it is preferable to described the observed phenotypic abnormalities precisely.
Polydactyly
A congenital anomaly characterized by the presence of supernumerary fingers or toes.
Syndactyly
Webbing or fusion of the fingers or toes, involving soft parts only or including bone structure. Bony fusions are revered to as "bony" syndactyly if the fusion occurs in a radio-ulnar axis. Fusions of bones of the fingers or toes in a proximo-distal axis are refered to as "symphalangism". Comment: Syndactyly may be partial or complete. In complete syndactyly, the skin is joined all the way to the fingertip. In partial (incomplete) syndactyly, the skin is only joined part of the distance to the fingertip.
Abnormality of male external genitalia
An abnormality of male external genitalia.
Abnormality of the female genitalia
Abnormality of the female genital system. Comment: Abnormality of the female internal or external genitalia.
Glucose intolerance
Diabetes mellitus
A group of abnormalities characterized by hyperglycemia and glucose intolerance.
Diabetes insipidus
A state of excessive water intake and hypotonic (dilute) polyuria. Diabetes insipidus may be due to failure of vasopressin (AVP) release (central or neurogenic diabetes insipidus) or to a failure of the kidney to respond to AVP (nephrogenic diabetes insipidus).
Chronic kidney disease
Functional anomaly of the kidney persisting for at least three months.
Abnormal renal morphology
Any structural anomaly of the kidney.
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.
Abnormality of cardiovascular system morphology
Any structural anomaly of the heart and great vessels.
Abnormality of the ear
An abnormality of the ear. Comment: Either a morphological abnormality or hearing deficit. This should be split more cleanly in the future.
Hyperlipidemia
An elevated lipid concentration in the blood. Comment: Hyperlipidemia is an elevation of the blood levels of lipids including primarily cholesterol, phospholipids and triglycerides and cholesterol esters. The lipids are transported on lipoproteins some of which are commonly used for clinical measurements, including chylomicrons, very-low density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), low-density lipoproteins, and high-density lipoproteins (HDL).
Abnormality of the middle ear ossicles
An abnormality of the middle-ear ossicles (three small bones called malleus, incus, and stapes) that are contained within the middle ear and serve to transmit sounds from the air to the fluid-filled labyrinth (cochlea).
Hypertension
The presence of chronic increased pressure in the systemic arterial system. Comment: Hypertension is sustained elevation of resting systolic BP (140 mm Hg or higher), diastolic BP (90 mm Hg or higher), or both.
Otitis media
Inflammation or infection of the middle ear.
Sensorineural hearing impairment
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve. Comment: Hearing loss caused by damage or dysfunction of the auditory nerve (cranial nerve VIII, also known as the cochlear nerve).
Conductive hearing impairment
An abnormality of vibrational conductance of sound to the inner ear leading to impairment of sensory perception of sound. Comment: A conductive hearing impariment with greater than 90 dB loss.
Dental crowding
Overlapping teeth within an alveolar ridge.
High palate
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). Comment: The measuring device for this assessment is described in (Hall JG, Froster-Iskenius UG, Allanson JE, Gripp K, Slavotinek A. 2006. Handbook of Normal Physical Measurements. 2nd edition. Oxford Medical, publishers). A high palate is often associated with a narrow palate. However, a narrow palate can easily give a false appearance of a high palate. Height and width of the palate should be assessed and coded separately. We do not recommend the subjective determination because this term can be overused and applied inaccurately.
Hepatic fibrosis
The presence of excessive fibrous connective tissue in the liver. Fibrosis is a reparative or reactive process.
Hepatic steatosis
The presence of steatosis in the liver. Comment: Steatosis refers to an abnormal accumulation of lipids within a cell or tissue.
Abnormality of the intrahepatic bile duct
An abnormality of the intrahepatic bile duct.
Elevated hepatic transaminases
Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage. Comment: previous def: 'has part' some ('increased amount' and ('inheres in' some (IMR_0000951 and ('part of' some blood))) and ('has modifier' some abnormal))
Autonomic bladder dysfunction
Abnormal bladder function (increased urge or frequency of urination or urge incontinence) resulting from abnormal functioning of the autonomic nervous system.
Ataxia
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- oder overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly). Comment: Ataxia can be differentiated into dyssynergy, asynergy, dysmetria (hypometria, hypermetria), dysdiadochokinesis, gait ataxia, truncal ataxia, limb ataxia, and dysarthria). Note: This term does not include sensory ataxia.
Spasticity
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Aganglionic megacolon
An abnormality resulting from a lack of intestinal ganglion cells (i.e., an aganglionic section of bowel) that results in bowel obstruction with enlargement of the colon. Comment: Aganglionic megacolon is characterized by congenital absence of intrinsic ganglion cells in the myenteric (Auerbach) and submucosal (Meissner) plexuses of the gastrointestinal tract.
Anosmia
An inability to perceive odors. This is a general term describing inability to smell arising in any part of the process of smelling from absorption of odorants into the nasal mucous overlying the olfactory epithelium, diffusion to the cilia, binding to olfactory receptor sites, generation of action potentials in olfactory neurons, and perception of a smell.
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- 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 Imaging Diagnostics