Proximal chromosome 18q deletion syndrome

Alternate names

Proximal 18q deletion syndrome; Proximal 18q-; Monosomy 18q syndrome; Proximal 18q deletion

Definition

Proximal chromosome 18q deletion syndrome is a chromosome abnormality that occurs when there is a missing (deleted) copy of genetic material from the part of the long (q) arm near the center of chromosome 18. The term "proximal" means that the missing piece occurs near the center of the chromosome.

Epidemiology

• Deletions from the q arm of chromosome 18 occur in an estimated 1 in 55,000 newborns worldwide.
• However, only a small number of these individuals have deletions in the region associated with proximal 18q deletion syndrome.
• At least 15 people with proximal 18q deletion syndrome have been described in the medical literature.

Cause

• Proximal 18q deletion syndrome is caused by a deletion of genetic material from one copy of chromosome 18.
• The deletion occurs near the middle of the q arm of the chromosome, typically in an area between regions called 18q11.2 and 18q21.2.
• The size of the deletion varies among affected individuals.
• The signs and symptoms of proximal 18q deletion syndrome are thought to be related to the loss of multiple genes from this part of chromosome 18.
• Researchers are working to determine how the loss of specific genes in this region contributes to the various features of this disorder.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

• Proximal 18q deletion syndrome is considered to be an autosomal dominant condition.
• This means that a deletion in one of the two copies of chromosome 18 in each cell is sufficient to cause the disorder's characteristic features.
• Most cases of proximal 18q deletion syndrome are the result of a new (de novo) deletion and are not inherited from a parent.
• The deletion occurs most often as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development.
• Affected people typically have no history of the disorder in their family.

Signs and symptoms

• The severity of the condition and the signs and symptoms depend on the size and location of the deletion and which genes are involved.
• Features that often occur in people with proximal chromosome 18q deletion syndrome include developmental delay, intellectual disability, and distinctive facial features.
• The might also have seizures, low muscle tone (hypotonia), speech and language delays, obesity, and short stature.
• Affected individuals also frequently have behavioral problems such as hyperactivity, aggression, and features of autism spectrum disorder that affect communication and social interaction.

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

30%-79% of people have these symptoms

• Abnormal facial shape(Unusual facial appearance)
• Abnormal myelination
• Abnormal palmar dermatoglyphics
• Abnormal retinal morphology(Retina issue)
• Arachnodactyly(Long slender fingers)
• Bilateral conductive hearing impairment
• Bilateral cryptorchidism
• Delayed skeletal maturation(Delayed bone maturation)
• Depressed nasal bridge(Depressed bridge of nose)
• Diffuse white matter abnormalities
• Downturned corners of mouth(Downturned corners of the mouth)
• Global developmental delay
• Intellectual disability, mild(Mental retardation, borderline-mild)
• Kyphoscoliosis
• Macrotia(Large ears)
• Mandibular prognathia(Big lower jaw)
• Micropenis(Short penis)
• Myopia(Close sighted)
• Neonatal hypotonia(Low muscle tone, in neonatal onset)
• Patent ductus arteriosus
• Pes planus(Flat feet)
• Poor coordination
• Pulmonary valve defects
• Secondary growth hormone deficiency
• Short stature(Decreased body height)
• Talipes equinovarus(Club feet)
• Tapered finger(Tapered fingertips)

5%-29% of people have these symptoms

• Absence of the pulmonary valve
• Aortic aneurysm(Bulge in wall of large artery that carries blood away from heart)
• Aortic valve stenosis(Narrowing of aortic valve)
• Biparietal narrowing
• Bulbous nose
• Cerebellar hypoplasia(Small cerebellum)
• Choanal stenosis(Narrowing of the rear opening of the nasal cavity)
• Choreoathetosis
• Congestive heart failure(Cardiac failure)
• Decreased circulating IgA level
• Downslanted palpebral fissures(Downward slanting of the opening between the eyelids)
• Dysplastic pulmonary valve
• Epicanthus(Eye folds)
• Failure to thrive(Faltering weight)
• High palate(Elevated palate)
• Hydrocephalus(Too much cerebrospinal fluid in the brain)
• Hypothyroidism(Underactive thyroid)
• Joint hypermobility(Double-Jointed)
• Left aortic arch with right descending aorta and right ductus arteriosus
• Left-to-right shunt
• Low anterior hairline(Low frontal hairline)
• Microcephaly(Abnormally small skull)
• Mitral regurgitation
• Open mouth(Gaped jawed appearance)
• Pectus excavatum(Funnel chest)
• Prominent nose(Big nose)
• Secundum atrial septal defect
• Seizure
• Sensorineural hearing impairment
• Short philtrum
• Slender build(Thin build)
• Strabismus(Cross-eyed)
• Thick vermilion border(Full lips)
• Wide mouth(Broad mouth)

1%-4% of people have these symptoms

• Astrocytoma
• Atlantoaxial abnormality

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, although it may also be made by microarray analysis.
• Prenatal diagnosis is possible via amniocentesis or chorionic villus sampling.
• 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.

NIH genetic and rare disease info

• NIH info on Proximal chromosome 18q deletion syndrome

Proximal chromosome 18q deletion syndrome is a rare disease.

Proximal chromosome 18q deletion syndrome Resources
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