Tetrasomy 18p is a genetic condition that is caused by the presence of an

isochromosome An isochromosome is an unbalanced structural abnormality in which the arms of the chromosome are mirror images of each other. The chromosome consists of two copies of either the long (q) arm or the short (p) arm because isochromosome formation ...

composed of two copies of the short arm of chromosome 18 in addition to the two normal copies of the chromosome. It is characterized by multiple medical and developmental concerns.

Signs and symptoms

Tetrasomy 18p causes a wide range of medical and developmental problems.Sebold C, Roeder E, Zimmerman M, Soileau B, Heard P, Carter E, Schatz M, White WA, Perry B, Reinker K, O'Donnell L, Lancaster J, Li J, Hasi M, Hill A, Pankratz L, Hale DE, Cody JD (2010). Tetrasomy 18p: report of the molecular and clinical findings of 43 individuals. Am J Med Genet 152A(9): 2164-72.

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 arteriosus ''Patent ductus arteriosus'' (PDA) is a medical condition in which the ''ductus arteriosus'' fails to close after birth: this allows a portion of oxygenated blood from the left heart to flow back to the lungs by flowing from the aorta, which has ...

is the most common defect. Septal defects (

ventricular septal defect A ventricular septal defect (VSD) is a defect in the ventricular septum, the wall dividing the left and right ventricles of the heart. The extent of the opening may vary from pin size to complete absence of the ventricular septum, creating one ...

s and

atrial septal defect Atrial septal defect (ASD) is a congenital heart defect in which blood flows between the atria (upper chambers) of the heart. Some flow is a normal condition both pre-birth and immediately post-birth via the foramen ovale; however, when this d ...

s) are also common, as are patent foramina ovalia. Other cardiac anomalies include

mitral valve regurgitation Mitral regurgitation (MR), also known as mitral insufficiency or mitral incompetence, is a form of valvular heart disease in which the mitral valve is insufficient and does not close properly when the heart pumps out blood. Section: Valvular Hea ...

, mitral valve prolapse, bicuspid pulmonary valve, hypoplastic transverse aortic arch, tricuspid valve regurgitation,

right ventricular hypertrophy Right ventricular hypertrophy (RVH) is a condition defined by an abnormal enlargement of the cardiac muscle surrounding the right ventricle. The right ventricle is one of the four chambers of the heart. It is located towards the lower-end of the h ...

, and

pulmonic stenosis Pulmonic stenosis, is a dynamic or fixed obstruction of flow from the right ventricle of the heart to the pulmonary artery. It is usually first diagnosed in childhood. Signs and symptoms Cause Pulmonic stenosis is usually due to isolated valvula ...

. In males,

cryptorchidism Cryptorchidism, also known as undescended testis, is the failure of one or both testes to descend into the scrotum. The word is from Greek () 'hidden' and () 'testicle'. It is the most common birth defect of the male genital tract. About 3% of ...

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, also known as ''ren arcuatus'' (in Latin), renal fusion or super kidney, is a congenital disorder affecting about 1 in 500 people that is more common in men, often asymptomatic, and usually diagnosed incidentally. In this disorder ...

and bladder diverticuli have been reported. Other abdominal malformations, including

pyloric stenosis Pyloric stenosis is a narrowing of the opening from the stomach to the first part of the small intestine (the pylorus). Symptoms include projectile vomiting without the presence of bile. This most often occurs after the baby is fed. The typical a ...

and

hernias A hernia is the abnormal exit of tissue or an organ, such as the bowel, through the wall of the cavity in which it normally resides. Various types of hernias can occur, most commonly involving the abdomen, and specifically the groin. Groin herni ...

, 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 is an abnormality of the hip joint where the socket portion does not fully cover the ball portion, resulting in an increased risk for joint dislocation. Hip dysplasia may occur at birth or develop in early life. Regardless, it doe ...

being the most common orthopedic issue.

Clubfoot Clubfoot is a birth defect where one or both feet are rotated inward and downward. Congenital clubfoot is the most common congenital malformation of the foot with an incidence of 1 per 1000 births. In approximately 50% of cases, clubfoot aff ...

and

rocker bottom feet Unlike the flexible flat foot that is commonly encountered in young children, congenital vertical talus is characterized by presence of a very rigid foot deformity. The foot deformity in congenital vertical talus consists of various components, nam ...

have also been reported.

Myelomeningocele Spina bifida (Latin for 'split spine'; SB) is a birth defect in which there is incomplete closing of the spine and the membranes around the spinal cord during early development in pregnancy. There are three main types: spina bifida occulta, men ...

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

jaundice Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...

are also relatively frequent.

ENT

Recurrent

otitis media Otitis media is a group of inflammatory diseases of the middle ear. One of the two main types is acute otitis media (AOM), an infection of rapid onset that usually presents with ear pain. In young children this may result in pulling at the ear, ...

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

The most common gastrointestinal abnormality is chronic

constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement ...

, though gastrointestinal reflux was also common.

Endocrine

Growth hormone deficiency Growth hormone deficiency (GHD), or human growth hormone deficiency, is a medical condition resulting from not enough growth hormone (GH). Generally the most noticeable symptom is that an individual attains a short height. Newborns may also prese ...

is present in about 20% of people with tetrasomy 18p.

Neurologic

Hypotonia Hypotonia is a state of low muscle tone (the amount of tension or resistance to stretch in a muscle), often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases a ...

and/or

hypertonia Hypertonia is a term sometimes used synonymously with spasticity and rigidity in the literature surrounding damage to the central nervous system, namely upper motor neuron lesions. Impaired ability of damaged motor neurons to regulate descending ...

are present in nearly all individuals with tetrasomy 18p. Approximately 25% have a

seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...

disorder.

Growth

Short stature is common, with ~50% being at or below the 25th centile and 20% being at or below the 3rd centile.

Microcephaly Microcephaly (from New Latin ''microcephalia'', from Ancient Greek μικρός ''mikrós'' "small" and κεφαλή ''kephalé'' "head") is a medical condition involving a smaller-than-normal head. Microcephaly may be present at birth or it ...

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.

Genetics

Tetrasomy 18p is caused by the presence of an additional isochromosome composed of two copies of the p arm of chromosome 18. This extra chromosome is classified as a

small supernumerary marker chromosome A small supernumerary marker chromosome (sSMC) is an abnormal extra chromosome. It contains copies of parts of one or more normal chromosomes and like normal chromosomes is located in the cell's nucleus, is replicated and distributed into each d ...

that forms ''de novo'' in a parent's egg or sperm or, in rare cases, is directly inherited from a parent carrier of the intact small supernumerary marker chromosome. It has been reported in both the non-mosaic as well as the

mosaic A mosaic is a pattern or image made of small regular or irregular pieces of colored stone, glass or ceramic, held in place by plaster/mortar, and covering a surface. Mosaics are often used as floor and wall decoration, and were particularly pop ...

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,Kotzot D, Bundscherer G, Bernasconi F, Brecevic L, Lurie IW, Basaran S, Baccicchetti C, H€oller A, Castellan C, Braun-Quentin C, Pfeiffer RA, Schinzel A. 1996. Isochromosome 18p results from maternal meiosis II nondisjunction. Eur J Hum Genet 4:168–174. 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 Specific developmental disorders (SDD) was a classification of disorders characterized by delayed development in one specific area or areas.Ahuja Vyas: ''Textbook of Postgraduate Psychiatry'' (2 Vols.), 2nd ed. 1999 Specific developmental disorders ...

congenital malformations A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can r ...

. 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 sampling Chorionic villus sampling (CVS), sometimes called "chorionic ''villous'' sampling" (as "villous" is the adjectival form of the word "villus"), is a form of prenatal diagnosis done to determine chromosomal or genetic disorders in the fetus. It ent ...

amniocentesis Amniocentesis is a medical procedure used primarily in the prenatal diagnosis of genetic conditions. It has other uses such as in the assessment of infection and fetal lung maturity. Prenatal diagnostic testing, which includes amniocentesis, is ne ...

. Severity of tetrasomy 18p is variable. Individuals with mosaicism are typically less severely affected than non-mosaic individuals.

Management

At present, treatment for tetrasomy 18p is symptomatic, 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:

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.

References

External links

{{Medical resources , ICD10 = Q99.8 , ICD9 = , ICDO = , OMIM = 614290 , DiseasesDB = , MedlinePlus = , eMedicineSubj = , eMedicineTopic = , MeSH = , GeneReviewsNBK = , GeneReviewsName = , Orphanet = 3307 Genetic disorders with no OMIM