Proximal 18q- is a rare

genetic condition A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...

caused by a deletion of genetic material within one of the two copies of

chromosome 18 Chromosome 18 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 18 spans about 80 million base pairs (the building material of DNA) and represents about 2.5 percent of the total DNA in ...

. This deletion involves the proximal (near the

centromere The centromere links a pair of sister chromatids together during cell division. This constricted region of chromosome connects the sister chromatids, creating a short arm (p) and a long arm (q) on the chromatids. During mitosis, spindle fibers a ...

) section of the long arm of chromosome 18 somewhere between 18q11.2 (18.9 Mb) to 18q21.1 (43.8 Mb).Cody JD, Sebold C, Malik A, Heard P, Carter E, Crandall A, Soileau B, Semrud-Clikeman M, Cody CM, Hardies LJ, Li J, Lancaster J, Fox PT, Stratton RF, Perry B, Hale DE (2007). Am J Med Genet 143A(11):1181-90. Exact breakpoints vary.

Signs and symptoms

Proximal 18q- causes a range of medical and developmental concerns. There is significant variation in severity due to the variation in breakpoints reported. Current research is focused on establishing genotype-phenotype correlations to enable predictive genotyping. A group of individuals with similar deletions within this region have been described (Cody et al., 2007): The medical and developmental problems are described below.

Congenital anomalies

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 ...

has been reported in some individuals. Although it is not a common finding,

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 ...

has been reported in some boys.

Neonatal complications

Feedings difficulties and problems with temperature regulation have been reported in some newborns with proximal 18q-.

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 frequently associated with proximal 18q- and, in some cases, may cause conductive hearing loss. This may be resolved with the placement of PE tubes.

Vision

Many individuals with proximal 18q- have

strabismus Strabismus is a vision disorder in which the eyes do not properly align with each other when looking at an object. The eye that is focused on an object can alternate. The condition may be present occasionally or constantly. If present during a ...

and/or

refractive errors Refractive error, also known as refraction error, is a problem with focusing light accurately on the retina due to the shape of the eye and or cornea. The most common types of refractive error are near-sightedness, far-sightedness, astigmatism, ...

Gastrointestinal anomalies

Gastrointestinal anomalies are not common in people with proximal 18q-, though there has been at least one individual reported that required g-tube feedings.

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 ...

is a common finding.

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

are present in about half of individuals.

MRI abnormalities

Hypoplasia of the

corpus callosum The corpus callosum (Latin for "tough body"), also callosal commissure, is a wide, thick nerve tract, consisting of a flat bundle of commissural fibers, beneath the cerebral cortex in the brain. The corpus callosum is only found in placental mam ...

, enlarged lateral ventricles, and Virchow-Robin perivascular spaces have all been reported in people with proximal 18q-.

Orthopedics

Orthopedic anomalies are commonly seen in people with proximal 18q-.

pes planus Flat feet (also called pes planus or fallen arches) is a postural deformity in which the arches of the foot collapse, with the entire sole of the foot coming into complete or near-complete contact with the ground. Sometimes children are born ...

, and

scoliosis Scoliosis is a condition in which a person's spine has a sideways curve. The curve is usually "S"- or "C"-shaped over three dimensions. In some, the degree of curve is stable, while in others, it increases over time. Mild scoliosis does not t ...

have all been reported.

Growth

Children with proximal 18q- are often small for their age. Unlike distal 18q-, however,

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 presen ...

has not been reported in anyone with proximal 18q-.

Development

Proximal 18q- causes developmental disabilities. Receptive language skills tend to be more advanced and can be near normal; however, expressive language skills are usually significantly delayed.

Genetics

Proximal 18q- is caused by an interstitial deletion of chromosome 18 involving the proximal region of the long arm of chromosome 18.

Diagnosis

Suspicion of a chromosome abnormality is typically raised due to the presence of developmental delays. Diagnosis of proximal 18q is usually made via a routine

chromosome analysis Cytogenetics is essentially a branch of genetics, but is also a part of cell biology/cytology (a subdivision of human anatomy), that is concerned with how the chromosomes relate to cell behaviour, particularly to their behaviour during mitosis an ...

, although it may also be made by microarray analysis.

Prenatal diagnosis Prenatal testing consists of prenatal screening and prenatal diagnosis, which are aspects of prenatal care that focus on detecting problems with the pregnancy as early as possible. These may be anatomic and physiologic problems with the health of ...

is possible via

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 ...

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 ...

. However, there have been multiple reports of missed prenatal diagnoses as the deletion can be difficult to identify on prenatal samples. In addition, small deletions within this region of the chromosome have been found in phenotypically normal individuals.

Treatment

At present, treatment for proximal 18q- is symptomatic, meaning that the focus is on treating the signs and symptoms of the condition as they arise.

Research

Currently, research is focusing on identifying the role of the genes on 18q in causing the signs and symptoms associated with proximal deletions of 18q.

References

External links

{{Chromosomal abnormalities Autosomal monosomies and deletions