Tetrasomy 18p
Encyclopedia
Tetrasomy 18p is a genetic condition that is caused by the presence of an isochromosome
, composed of two copies of the short arm of chromosome 18. It is characterized by multiple medical and developmental concerns.
or amniocentesis
.
is the most common defect. Septal defects (ventricular septal defects
and atrial septal defects
) are also common, as are patent foramina ovalia. Other cardiac anomalies, including mitral valve regurgitation; mitral valve prolapse
; bicuspid pulmonary valve; hypoplastic transverse aortic arch; tricuspid valve regurgitation; right ventricular hypertrophy
; and pulmonic stenosis
.
In males, cryptorchidism
is common. Abnormal genitalia in females is not a common feature. Renal abnormalities have been reported in a minority of patients. Horseshoe kidney
and bladder diverticuli have been reported. Other abdominal malformations, including pyloric stenosis
and hernias, have also been reported, though they are present in only a minority of patients.
Orthopedic anomalies also occur relatively frequently, with hip dysplasia
being the most common orthopedic issue. Clubfoot and rocker bottom feet have also been reported.
Myelomeningocele is another known feature associated with tetrasomy 18p.
are also relatively frequent.
is common, and many patients required the placement of PE tubes. Small ear canals are also fairly common, but not as much as in 18q-.
, though gastrointestinal reflux
was also common.
and/or hypertonia
are present in nearly all individuals with tetrasomy 18p. Approximately 25% have a seizure
disorder.
is present in about 40% of patients.
Chromosome 18 Clinical Research Center, University of Texas Health Science Center at San Antonio
Isochromosome
An isochromosome is a chromosome that has lost one of its arms and replaced it with an exact copy of the other arm. This is sometimes seen in some females with Turner syndrome or in tumor cells. This may also cause an isochromosome to have two centromeres The chromosome arm is already copied during...
, composed of two copies of the short arm of chromosome 18. It is characterized by multiple medical and developmental concerns.
Genetic Basis
Tetrasomy 18p is caused by the presence of an additional isochromosome composed of two copies of the p arm of chromosome 18. It has been reported in both the non-mosaic as well as the mosaic state. (The phrase "mosaicism" in this context means that some cells carry the genetic change while others do not.) In the grand majority of cases, the isochromosome is de novo. Although there has been some speculation that tetrasomy 18p may occur with a higher frequency in children of older mothers, there is not enough evidence to say that this is definitively the case.Diagnosis
Suspicion of a chromosome abnormality is typically raised due to the presence of developmental delays or congenital malformations. Diagnosis of tetrasomy 18p is typically made via a routine chromosome analysis from a blood sample. The diagnosis can also be made prenatally by chorionic villus samplingChorionic villus sampling
Chorionic villus sampling , sometimes misspelled "chorionic villous sampling", is a form of prenatal diagnosis to determine chromosomal or genetic disorders in the fetus. It entails sampling of the chorionic villus and testing it...
or amniocentesis
Amniocentesis
Amniocentesis is a medical procedure used in prenatal diagnosis of chromosomal abnormalities and fetal infections, in which a small amount of amniotic fluid, which contains fetal tissues, is sampled from the amnion or amniotic sac surrounding a developing fetus, and the fetal DNA is examined for...
.
Clinical Description
Tetrasomy 18p causes a wide range of medical and developmental problems .Congenital Anomalies
Cardiac anomalies are the most common congenital malformation in individuals with tetrasomy 18p. However, there is no pathognomatic heart defect associated with the condition. Patent ductus arteriosusPatent ductus arteriosus
Patent ductus arteriosus is a congenital disorder in the heart wherein a neonate's ductus arteriosus fails to close after birth. Early symptoms are uncommon, but in the first year of life include increased work of breathing and poor weight gain...
is the most common defect. Septal defects (ventricular septal defects
Ventricular septal defect
A ventricular septal defect is a defect in the ventricular septum, the wall dividing the left and right ventricles of the heart.The ventricular septum consists of an inferior muscular and superior membranous portion and is extensively innervated with conducting cardiomyocytes.The membranous...
and atrial septal defects
Atrial septal defect
Atrial septal defect is a form of congenital heart defect that enables blood flow between the left and right atria via the interatrial septum. The interatrial septum is the tissue that divides the right and left atria...
) are also common, as are patent foramina ovalia. Other cardiac anomalies, including mitral valve regurgitation; mitral valve prolapse
Mitral valve prolapse
Mitral valve prolapse is a valvular heart disease characterized by the displacement of an abnormally thickened mitral valve leaflet into the left atrium during systole. There are various types of MVP, broadly classified as classic and nonclassic. In its nonclassic form, MVP carries a low risk of...
; bicuspid pulmonary valve; hypoplastic transverse aortic arch; tricuspid valve regurgitation; right ventricular hypertrophy
Right ventricular hypertrophy
Right ventricular hypertrophy is a form of ventricular hypertrophy affecting the right ventricle.Blood travels through the right ventricle to the lungs via the pulmonary arteries. If conditions occur which decrease pulmonary circulation, meaning blood does not flow well from the heart to the...
; and pulmonic stenosis
Pulmonic stenosis
Pulmonic stenosis, also known as Pulmonary stenosis, is a dynamic or fixed obstruction to flow from the right ventricle of the heart to the pulmonary artery. It is usually first diagnosed in childhood....
.
In males, cryptorchidism
Cryptorchidism
Cryptorchidism is the absence of one or both testes from the scrotum. It is the most common birth defect regarding male genitalia. In unique cases, cryptorchidism can develop later in life, often as late as young adulthood. About 3% of full-term and 30% of premature infant boys are born with at...
is common. Abnormal genitalia in females is not a common feature. Renal abnormalities have been reported in a minority of patients. Horseshoe kidney
Horseshoe kidney
Horseshoe kidney, also known as renal fusion or super kidney, is a congenital disorder affecting about 1 in 400 people. In this disorder, the patient's kidneys fuse together to form a horseshoe-shape during development in the womb...
and bladder diverticuli have been reported. Other abdominal malformations, including pyloric stenosis
Pyloric stenosis
Pyloric stenosis is a condition that causes severe vomiting in the first few months of life. There is narrowing of the opening from the stomach to the intestines, due to enlargement of the muscle surrounding this opening , which spasms when the stomach empties...
and hernias, have also been reported, though they are present in only a minority of patients.
Orthopedic anomalies also occur relatively frequently, with hip dysplasia
Hip dysplasia
Hip dysplasia is an abnormal formation of the hip socket that, in its more severe form, can eventually cause crippling lameness and painful arthritis of the joints. It is a genetic trait that is affected by environmental factors...
being the most common orthopedic issue. Clubfoot and rocker bottom feet have also been reported.
Myelomeningocele is another known feature associated with tetrasomy 18p.
Neonatal Complications
Neonatal complications (apart from congenital anomalies) are common. In a paper published in 2010, 41 of 42 individuals had some type medical problem in the first days of life, the most common being feeding difficulties. Respiratory difficulty and jaundiceNeonatal jaundice
Neonatal jaundice or Neonatal hyperbilirubinemia is a yellowing of the skin and other tissues of a newborn infant. A bilirubin level of more than 85 umol/l manifests clinical jaundice in neonates whereas in adults a level of 34 umol/l would look icteric...
are also relatively frequent.
ENT
Recurrent otitis mediaOtitis media
Otitis media is inflammation of the middle ear, or a middle ear infection.It occurs in the area between the tympanic membrane and the inner ear, including a duct known as the eustachian tube. It is one of the two categories of ear inflammation that can underlie what is commonly called an earache,...
is common, and many patients required the placement of PE tubes. Small ear canals are also fairly common, but not as much as in 18q-.
Gastrointestinal Anomalies
The most common gastrointestinal abnormality is chronic constipationConstipation
Constipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...
, though gastrointestinal reflux
Reflux
Reflux is a technique involving the condensation of vapors and the return of this condensate to the system from which it originated. It is used in industrial and laboratory distillations...
was also common.
Neurologic
HypotoniaHypotonia
Hypotonia is a state of low muscle tone , often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength...
and/or hypertonia
Hypertonia
Hypertonia a condition marked by an abnormal increase in muscle tension and a reduced ability of a muscle to stretch. It is caused by lesions to upper motor neurons in the central nervous system, which carry information from the central nervous system to the muscles and control posture, muscle...
are present in nearly all individuals with tetrasomy 18p. Approximately 25% have a seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...
disorder.
Growth
Short stature is common, with ~50% being at or below the 25th centile and 20% being at or below the 3rd centile. MicrocephalyMicrocephaly
Microcephaly is a neurodevelopmental disorder in which the circumference of the head is more than two standard deviations smaller than average for the person's age and sex. Microcephaly may be congenital or it may develop in the first few years of life...
is present in about 40% of patients.
Development
All reported cases of tetrasomy 18p have some degree of intellectual disability. Most individuals score in the moderate range of intellectual disability based on standardized testing.Variability
Severity of tetrasomy 18p is variable. Individuals with mosaicism are typically less severely affected than non-mosaic individuals.Treatment/Management
At present, treatment for tetrasomy 18p is empiric, meaning that the focus is on treating the signs and symptoms of the conditions as they arise. The Chromosome 18 Clinical Research Center has published a list of recommended screening and evaluations :- Genetics evaluation and counseling
- Parental chromosomes
- Periodic opthalmology evaluations
- Periodic audiology evaluations
- ENT referral for management of chronic otitis media
- Cardiology evaluation
- Renal ultrasound
- Orthopedic evaluation for management of foot abnormalities
- Monitor for scoliosis and kyphosis
- Neurology evaluation for seizures, abnormal muscle tone
- Gastrointestinal/nutritional evaluation of failure to thrive, gastroesophageal reflux, constipation
- Endocrinology evaluation for short stature, to include evaluation for growth hormone deficiency
- Referral for developmental services and therapy
Current Research
Current research is focusing on clearly defining the phenotype associated with tetrasomy 18p and identifying which genes cause medical and developmental problems when present in four copies.Support resources
The Chromosome 18 Registry & Research SocietyChromosome 18 Clinical Research Center, University of Texas Health Science Center at San Antonio