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Relevant diseases: - Classical Beckwith-Wiedemann syndrome - Atypical Beckwith-Wiedemann syndrome
Inclusion Criteria
Clinical diagnosis of BWS meeting standard clinical diagnostic criteria EXCEPT THOSE WITH UPD 11p15, UNBALANCED TRANSLOCATIONS OR OTHER 11p15 COPY NUMBER DEFECTS OR CDKN1C MUTATIONS Eligible patients will include those with No detectable cause Balanced chromosomal aberration (translocation/inversion) Multilocus methylation defect consistent with an in trans imprinting defect Isolated/single locus 11p15 methylation defect Recruitment of families with Isolated/single locus methylation defects without a family history or BWS or other imprinted disorder should only occur as proband-mother-father trios.
Exclusion Criteria
Those with: UPD 11p15 Unbalanced translocations or other 11p15 copy number defects CDKN1C mutations
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
11p15 methylation testing is required PRIOR TO RECRUITMENT as molecular diagnosis determines eligibility and surveillance, and methylation abnormalities cannot be detected on WGS. - Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice: CDKN1C
Closing Statement
These requirements will be kept under continual review during the main programme and may be subject to change.
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Overgrowth
Excessive postnatal growth which may comprise increased weight, increased length, and/or increased head circumference.
Preeclampsia
Pregnancy-induced hypertension in association with significant amounts of protein in the urine.
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.
Large placenta
Increased size of the placenta.
Neonatal hypoglycemia
Feeding difficulties in infancy
Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.
Apnea
Lack of breathing with no movement of the respiratory muscles and no exchange of air in the lungs. This term refers to a disposition to have recurrent episodes of apnea rather than to a single event.
Apneic episodes in infancy
Recurrent episodes of apnea occurring during infancy.
Cyanosis
A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule.
Accelerated skeletal maturation
An abnormally increased rate of skeletal maturation. Accelerated skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.
Asymmetric growth
A growth pattern that displays an abnormal difference between the left and the right side.
Hemihypertrophy
Overgrowth of only one side of the body.
Facial asymmetry
An abnormal difference between the left and right sides of the face.
Hemihypertrophy of upper limb
Overgrowth of only one arm.
Asymmetry of the thorax
Lack of symmetry between the left and right halves of the thorax.
Hemihypertrophy of lower limb
Overgrowth of only one leg.
Nevus flammeus
A congenital vascular malformation consisting of superficial and deep dilated capillaries in the skin which produce a reddish to purplish discolouration of the skin. Comment: Port-wine stains generally become deeper, thicker, and darker in color over time, mainly as a result of progressive vascular dilatation. As a result of these changes, which are generally much more evident on the face, patients often develop hypertrophy and nodularity after the third or fourth decade of life. The fact that nodules are only found on the face and do not occur in childhood has led some authors to suggest that port-wine stains might actually be hamartomatous lesions.
Macroglossia
Increased length and width of the tongue. Comment: Normal standards do not exist. Large size usually leads to protrusion of the tongue. This is an acknowledged bundled term, but due to its frequent usage and relative paucity of situations that would call for separate individual assessments of tongue dimensions, the bundled term is retained. Micrognathia may give the false appearance of a large tongue.
Mandibular prognathia
Abnormal prominence of the chin related to increased length of the mandible.
Prominent occiput
Increased convexity of the occiput (posterior part of the skull). Comment: Increased convexity of the occiput gives an appearance of prominence. There are no objective measures for convexity of the occiput, and evaluation depends heavily on the experience of the observer. This finding may or may not be accompanied by Dolichocephaly, but this should be coded separately.
Aplasia/Hypoplasia of the maxilla
Absence or underdevelopment of the Maxilla.
Anterior creases of earlobe
Sharply demarcated, typically linear and approximately horizontal, indentations in the outer surface of the ear lobe. Comment: Shallow grooves or indentations are quite common, especially in large lobes. Ear lobe creases may arise postnatally. Posterior helical pits can be a related finding but should be assessed and coded separately.
Posterior helix pit
Permanent indentation on the posteromedial aspect of the helix that may be sharply or indistinctly delineated. Comment: They are usually linear to a narrow oval in shape and may be single or multiple.
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.
Polycythemia
Polycythemia is diagnosed if the red blood cell count, the hemoglobin level, and the red blood cell volume all exceed the upper limits of normal.
Ventricular septal defect
A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum.
Atrial septal defect
Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum.
Tetralogy of Fallot
A congenital cardiac malformation comprising pulmonary stenosis, overriding aorta, ventricular septum defect, and right ventricular hypertrophy. The diagnosis of TOF is made if at least three of the four above mentioned features are present.
Coarctation of aorta
Coarctation of the aorta is a narrowing or constriction of a segment of the aorta. Comment: Coarctation refers to a narrowing of the lumen of a vessel producing an obstruction to flow. Coarctation can occur in any region of the aorta.
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.
Abdominal wall defect
An incomplete closure of the abdominal wall.
Omphalocele
A midline anterior incomplete closure of the abdominal wall in which there is herniation of the abdominal viscera into the base of the abdominal cord.
Umbilical hernia
Protrusion of abdominal contents through a defect in the abdominal wall musculature around the umbilicus. Skin and subcutaneous tissue overlie the defect.
Malrotation of small bowel
A deviation from the normal rotation of the midgut during embryologic development with mislocalization of the small bowel. Comment: Malrotation results not only in the malposition of the bowel but also in the malfixation of the mesentery. The normally broad mesenteric attachment is shortened to a narrow pedicle that predisposes the patient to the complication of midgut volvulus.
Enlarged kidney
An abnormal increase in the size of the kidney. Comment: The main causes of large kidney are hydronephrosis, polycystic disease, renal cell carcinoma, nephroblastoma/Wilm's tumor (in children), and solitary cysts. If possible, a specific term should be used instead of this one. There are several ways of diagnosing enlarged kidney including intravenous urography.
Splenomegaly
Abnormal increased size of the spleen.
Hepatomegaly
Abnormally increased size of the liver.
Hypospadias
Displacement of the urethral opening on the ventral (inferior) surface of the penis.
Cryptorchidism
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 testis. Comment: The gonad is mobile and can be retracted superiorly by the cremaster muscle reflex stimulated, for instance, by cold or touch. A retracted testis is not cryptorchidism. An abdominal testis cannot be distinguished by physical examination from an (Apparently) absent testis and requires radiological (or, rarely, surgical) procedures for assessment.
Inguinal hernia
Protrusion of the contents of the abdominal cavity through the inguinal canal. Comment: Inguinal hernia appears as a bulge in the groin.
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.
Delayed gross motor development
A type of motor delay characterized by an delay in acquiring the ability to control the large muscles of the body for walking, running, sitting, and crawling.
Delayed fine motor development
A type of motor delay characterized by an delay in acquiring the ability to control the fingers and hands.
Delayed speech and language development
A degree of language development that is significantly below the norm for a child of a specified age. Comment: Language delay can be characterized by a failure to meet the developmental milestones for language development, an inability to follow directions, or slow or incomprehensible speech after the age of three years, as well as with severe problems with syntax or articulation.
Specific learning disability
Impairment of certain skills such as reading or writing, coordination, self-control, or attention that interfere with the ability to learn. The impairment is not related to a global deficiency of intelligence. Comment: The term learning disability is used with different meanings in different contexts. Significant impairments of mental functioning with a reduction in IQ below 70 should be coded as mental retardation.
Autistic behavior
A disorder beginning in childhood. It is marked by the presence of markedly abnormal or impaired development in social interaction and communication and a markedly restricted repertoire of activity and interest. Manifestations of the disorder vary greatly depending on the developmental level and chronological age of the individual (DSM-IV). Comment: This term can be used to refer to autism spectrum disorder as a phenotypic feature that can be a component of a disease. Autism spectrum disorder range from a severe form, called autistic disorder, to a milder form, Asperger syndrome.
Attention deficit hyperactivity disorder
Attention deficit hyperactivity disorder (ADHD) manifests at age 2-3 years or by first grade at the latest. The main symptoms are distractibility, impulsivity, hyperactivity, and often trouble organizing tasks and projects, difficulty going to sleep, and social problems from being aggressive, loud, or impatient.
Abnormal social behavior
An abnormality of actions or reactions of a person taking place during interactions with others.
Abnormal emotion/affect behavior
An abnormality of emotional behaviour.
Visual impairment
Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery.
Hearing impairment
A decreased magnitude of the sensory perception of sound. Comment: Hearing loss can be categorized by which part of the auditory system is damaged, as conductive hearing loss, sensorineural hearing loss, and mixed hearing loss. Another axis of classification uses the degree of hearing impairment. The degree of hearing loss is computed by using a three frequency average taken at 500 Hz, 1,000 Hz and 2,000 Hz. The average of these three frequencies is called the Pure Tone Average (PTA). 0-20 dB is considered normal, 21-40 dB mild loss, 41-60 dB moderate loss, 61-70 dB moderately severe loss,71-90 dB severe loss, and greater than 90 dB profound loss. Note that the word deafness is occasionally used to describe partial hearing loss. The World Health Organization uses the word deafness to refer to complete loss of the ability to hear, and hearing impairment to refer to any degree of reduced hearing.
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.
Nephroblastoma
The presence of a nephroblastoma, which is a neoplasm of the kidney that primarily affects children. Comment: Nephroblastoma is characterized by an abnormal proliferation of the metanephric blastema cells, which are believed to be primitive embryologic cells of the kidney. Clinically, nephroblatoma usually presents as an abdominal mass, and in some cases with abdominal pain, hypertension, hematuria, and fever.
Neuroblastoma
Neuroblastoma is a solid tumor that originate in neural crest cells of the sympathetic nervous system. Most neuroblastomas originate in the abdomen, and most abdominal neuroblastomas originate in the adrenal gland. Neuroblastomas can also originate in the thorax, usually in the posterior mediastinum.
Hepatoblastoma
A kind of neoplasm of the liver that originates from immature liver precursor cells and macroscopically is composed of tissue resembling fetal or mature liver cells or bile ducts. Comment: Hepatoblastoma occurs nearly exclusively in infants and children.
Neoplasm of the adrenal cortex
The presence of a neoplasm of the adrenal cortex.
Rhabdomyosarcoma
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- Additional body measurements