Genetic counseling: 18q Deletion Syndrome

18q Deletion Syndrome

Genetic Etiology

 * Caused by the deletion of the long arm of chromosome 18 (or, more often, a section of it)

Incidence and Carrier Frequency

 * This disorder has been documented in less than 100 cases
 * 80% of cases occur due to de novo mutations; 10% of cases are due to a parental translocation; the remaining 10% are mosaic, resulting in a less severe phenotype

Clinical Features
This syndrome is variable in its severity. The symptoms usually correlate with the size of the deletion.

Key features:
 * Short stature (80% of patients are below the fifth percentile)
 * Mental impairment/retardation (100% of patients, most with IQs from 40-85)
 * Hypotonia
 * Hearing impairment (61%)
 * Ear anomalies
 * Narrow or atretic auditory canals (50%)
 * Prominent antihelix or antitragus (84%)
 * Low-set ears
 * Foot deformities
 * Club foot (21%)
 * Abnormal implantation of the second toe (84%)
 * Endocrine problems
 * IgA deficiency (30%)
 * Growth hormone deficiency
 * Facial dysmorphism
 * Microcephaly (68%)
 * "Carp-like" mouth (87%)
 * Midface hypoplasia (85%)
 * Deeply-set eyes
 * Slanted palpebral fissures
 * Hypertelorism
 * Epicanthic folds (42%)
 * Strabismus (34%)
 * Nystagmus (80%)
 * Pale optic discs (84%)
 * Broad nasal bridge (81%)
 * Cleft lip (9%)
 * Cleft palate (29%)
 * Abnormal genitalia
 * Females: hypoplastic labia minora (47%)
 * Males: cryptorchidism (52%), hypospadias, micropenis, inguinal hernia (13%)
 * Poor myelination of central white matter tracts with relatively normal myelination of corpus callosum
 * Hand anomalies
 * Tapered fingers (90%)
 * Proximal thumb with short first metacarpal
 * Transverse palmar creases (92%)
 * High whorl patterns on fingertips and high total finger ridge count
 * Dimples on the knuckles

Age of onset, natural history, life span

 * Symptoms are apparent from birth in most cases
 * Natural history: Most patients have IQs between 40 and 85. Short stature is common, as are various hearing and vision problems. Behavioral problems can often occur, causing patients to exhibit autistic-like behaviors or obnoxiousness. These symptoms are variable, so a patient with a smaller deletion will have a milder phenotype than will a patient missing all of 18q.
 * Life span is variable, but decreased from the general population

Testing
Diagnosis is confirmed by chromosome studies

Surveillance, management, and treatment options
Patients should be monitored by audiology, opthamology, genetics, neurology, orthopedics, immunology, physical therapy, occupational therapy, speech therapy, and Early Intervention.

Psychosocial issues
Guilt, fear, anxiety, anger, sadness, and disbelief are common emotions associated with this diagnosis. Parents may feel overwhelmed because of all of the care these patients require. Financial concerns, issues affecting family dynamics, and who will provide care for this patient are all things that should be addressed with parents.