18p- is a genetic condition caused by a deletion of all or part of the short arm (the p arm) of chromosome 18. It occurs in about 1 of every 40,000 births.

Nomenclature

The preferred terminology for this condition is 18p-. In the past, it has been referred to as partial monosomy 18p and, rarely, as “de Grouchy syndrome, type 1".

Genetic Basis

18p- describes a deletion of the short arm of chromosome 18. About half of the people with deletions have a breakpoint at the centromere

Centromere

A centromere is a region of DNA typically found near the middle of a chromosome where two identical sister chromatids come closest in contact. It is involved in cell division as the point of mitotic spindle attachment...

.

Diagnosis

Suspicion of a chromosome abnormality is typically raised due to the presence of developmental delays or birth defects. Diagnosis of 18p- is usually made via a blood sample. A routine chromosome analysis, or karyotype

Karyotype

A karyotype is the number and appearance of chromosomes in the nucleus of an eukaryotic cell. The term is also used for the complete set of chromosomes in a species, or an individual organism.p28...

, is usually used to make the initial diagnosis, although it may also be made by microarray analysis. Increasingly, microarray analysis is also being used to clarify breakpoints. Prenatal diagnosis

Prenatal diagnosis

Prenatal diagnosis or prenatal screening is testing for diseases or conditions in a fetus or embryo before it is born. The aim is to detect birth defects such as neural tube defects, Down syndrome, chromosome abnormalities, genetic diseases and other conditions, such as spina bifida, cleft palate,...

 is possible via 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...

 of chorionic villus sampling

Chorionic 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...

.

Clinical Description

18p- causes a wide range of medical and developmental concerns. There is significant variation in severity. This variation is due to the variability of the deletion size and breakpoints.

Congenital Anomalies

About 10-15% of individuals with 18p- have holoprosencephaly

Holoprosencephaly

Holoprosencephaly is a cephalic disorder in which the prosencephalon fails to develop into two hemispheres. Normally, the forebrain is formed and the face begins to develop in the fifth and sixth weeks of human pregnancy...

.

Approximately 10% of people with 18p- have a congenital heart anomaly. There does not appear to be a specific type of heart defect associated with a deletion of the short arm of chromosome 18. Septal defects, tetralogy of Fallot

Tetralogy of Fallot

Tetralogy of Fallot is a congenital heart defect which is classically understood to involve four anatomical abnormalities...

, dextrocardia

Dextrocardia

Dextrocardia is a congenital defect in which the heart is situated on the right side of the body. There are two main types of dextrocardia: dextrocardia of embryonic arrest and dextrocardia situs inversus...

, and coarctation of the aorta have all been reported in infants with 18p-.

Neurologic

Hypotonia

Hypotonia

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...

 is frequently seen in the 18p- population. Seizures, though uncommon, have been reported in people with 18p-. Dystonia

Dystonia

Dystonia is a neurological movement disorder, in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures. The disorder may be hereditary or caused by other factors such as birth-related or other physical trauma, infection, poisoning or reaction to...

 has also been diagnosed in a small minority of young adults with 18p-. Also, tethered cord has been reported in a few people with 18p-.

MRI Abnormalities

In some children without “classic” holoprosencephaly, microforms of holoprosencephaly may be noted on MRI, including missing olfactory tracts and bulbs

Olfactory bulb

The olfactory bulb is a structure of the vertebrate forebrain involved in olfaction, the perception of odors.-Anatomy:In most vertebrates, the olfactory bulb is the most rostral part of the brain. In humans, however, the olfactory bulb is on the inferior side of the brain...

 and absent or hypoplastic corpus callosum

Corpus callosum

The corpus callosum , also known as the colossal commissure, is a wide, flat bundle of neural fibers beneath the cortex in the eutherian brain at the longitudinal fissure. It connects the left and right cerebral hemispheres and facilitates interhemispheric communication...

.

Vision

Ptosis

Ptosis

Ptosis refers to droopiness of a body part. Specifically, it can refer to:* Ptosis * Ptosis * Enteroptosis * Gastroptosis...

 is quite common among people with 18p-. In many cases, surgical correction is required. Refractive errors, such as myopia

Myopia

Myopia , "shortsightedness" ) is a refractive defect of the eye in which collimated light produces image focus in front of the retina under conditions of accommodation. In simpler terms, myopia is a condition of the eye where the light that comes in does not directly focus on the retina but in...

, hyperopia

Hyperopia

Hyperopia, also known as farsightedness, longsightedness or hypermetropia, is a defect of vision caused by an imperfection in the eye , causing difficulty focusing on near objects, and in extreme cases causing a sufferer to be unable to focus on objects at any distance...

, and astigmatism

Astigmatism

An optical system with astigmatism is one where rays that propagate in two perpendicular planes have different foci. If an optical system with astigmatism is used to form an image of a cross, the vertical and horizontal lines will be in sharp focus at two different distances...

, are also prevalent. Strabismus

Strabismus

Strabismus is a condition in which the eyes are not properly aligned with each other. It typically involves a lack of coordination between the extraocular muscles, which prevents bringing the gaze of each eye to the same point in space and preventing proper binocular vision, which may adversely...

 has been reported in infants and children with 18p-. Nystagmus

Nystagmus

Nystagmus is a condition of involuntary eye movement, acquired in infancy or later in life, that may result in reduced or limited vision.There are two key forms of Nystagmus: pathological and physiological, with variations within each type. Nystagmus may be caused by congenital disorders,...

 is also present in a minority of individuals.

Ear and Sinus Infections

Children with 18p- have an increased incidence of ear infections, often requiring the placement of PE tubes.

Gastrointestinal

Chronic constipation

Constipation

Constipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...

 is a frequent complaint in the 18p- population. Other abdominal abnormalities that have been reported include inguinal hernias; malrotation of the gut; and abnormalities of the spleen.

Genitourinary

Genitourinary abnormalities are not common in 18p-. There have been a few cases of small penis and 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...

 in males and uterine abnormalities in females.

Orthopedics

There have been several orthopedic concerns identified in individuals with 18p-. These include pes planus, clubfoot, scoliosis

Scoliosis

Scoliosis is a medical condition in which a person's spine is curved from side to side. Although it is a complex three-dimensional deformity, on an X-ray, viewed from the rear, the spine of an individual with scoliosis may look more like an "S" or a "C" than a straight line...

 and/or kyphosis

Kyphosis

Kyphosis , also called roundback or Kelso's hunchback, is a condition of over-curvature of the thoracic vertebrae...

, pectus

Pectus

Pectus may refer to:* Pectus excavatum* Pectus carinatum...

 abnormalities, cubitus valgus

Cubitus valgus

Cubitus valgus is a medical deformity in which the elbows are turned in. A small degree of cubitus valgus is acceptable and occurs in the general population....

, congenital hip dysplasia

Hip dysplasia (human)

Hip dysplasia, developmental dysplasia of the hip or congenital dysplasia of the hip is a congenital or acquired deformation or misalignment of the hip joint.-Terminology:...

, spina bifida occulta, and genu valgus.

Endocrinology

Growth hormone deficiency

Growth hormone deficiency

Growth hormone deficiency is a medical condition in which the body does not produce enough growth hormone . Growth hormone, also called somatotropin, is a polypeptide hormone which stimulates growth and cell reproduction...

 has been reported in several individuals with 18p-, though not at the same frequency as in the distal 18q- population. Panhypopituitarism and hypothyroidism

Hypothyroidism

Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...

 have each been diagnosed in a handful of individuals

Psychiatry

There is an increased incidence of psychiatric conditions within the distal 18p- population. In one study, 2 of 3 people with 18p- had an anxiety disorder

Anxiety disorder

Anxiety disorder is a blanket term covering several different forms of abnormal and pathological fear and anxiety. Conditions now considered anxiety disorders only came under the aegis of psychiatry at the end of the 19th century. Gelder, Mayou & Geddes explains that anxiety disorders are...

, 1 of 3 had a communication disorder

Communication disorder

A communication disorder is a speech and language disorder which refers to problems in communication and in related areas such as oral motor function. The delays and disorders can range from simple sound substitution to the inability to understand or use language...

, and 1 of 3 had a motor skills disorders

Motor skills disorder

Motor skills disorder is a human developmental disorder that impairs motor coordination in daily activities. It is neurological in origin...

, and 1 of 3 had a stereotypic movement disorder

Stereotypic movement disorder

Stereotypic movement disorder is a disorder of childhood involving repetitive, nonfunctional motor behavior , that markedly interferes with normal activities or results in bodily injury, and persists for four weeks or longer. The behavior must not be due to the direct effects of a substance or...

. Additional research with a larger number of subjects is necessary to confirm these findings.

Cognition and adaptive skills

Cognitive ability in individuals with 18p- varies widely, with most falling in the mild to moderate range of impairment, though there have been some reports of people with impairment in the severe to profound range. These individuals may have had holoprosencephaly, which is frequently associated with severe impairment.

Speech deficits are quite common within this population. Frequently, expressive speech lags behind other developmental parameters.

Dysmorphology

Common facial features include a flat and broad nasal bridge; epicanthic folds; wide mouth; short philtrum

Philtrum

The philtrum , is a medial cleft common to many mammals, extending from the nose to the upper lip, and, together with a glandular rhinarium and slit-like nostrils, is believed to constitute the primitive condition for mammals in general...

; everted lower lip; small and slightly receding chin during childhood. The ears may be low-set and posteriorly rotated. The posterior hairline may be low.

Treatment

At present, treatment for 18p- is empiric, meaning that the focus is on treating the signs and symptoms of the conditions as they arise. To ensure early diagnosis and treatment, it is suggested that people with 18p- undergo routine screenings for hearing and vision problems.

Current Research

Currently, research is focusing on identifying the role of the genes on 18p in causing the signs and symptoms associated with deletions of 18p. This will ultimately enable predictive genotyping

Genotyping

Genotyping is the process of determining differences in the genetic make-up of an individual by examining the individual's DNA sequence using biological assays and comparing it to another individual's sequence or a reference sequence. It reveals the alleles an individual has inherited from their...

.

TGIF-Mutations and deletions of this gene have been associated with holoprosencephaly. Penetrance

Penetrance

Penetrance in genetics is the proportion of individuals carrying a particular variant of a gene that also express an associated trait . In medical genetics, the penetrance of a disease-causing mutation is the proportion of individuals with the mutation who exhibit clinical symptoms...

is incomplete, meaning that a deletion of one copy of this gene is not in and of itself sufficient to cause holoprosencephaly. Ten to fifteen percent of people with 18p- have holoprosencephaly, suggesting that other genetic and environmental facts play a role in the etiology of holoprosencephaly in these individuals.

Support Resources

The Chromosome 18 Registry & Research Society

Chromosome 18 Clinical Research Center, University of Texas Health Science Center at San Antonio

Unique

Chromosome Disorder Outreach