18p deletion syndrome

Disease Description (Causes and Symptoms)

• Definition: 18p monosomy is a rare chromosomal abnormality caused by partial or complete deletion of the short arm (p arm) of chromosome 18, accompanied by characteristic facial abnormalities and developmental delay.
• Cause/Inheritance:
  • Approximately 85% result from spontaneous (de novo) deletions.
  • The remainder may be inherited from a structural chromosomal abnormality carried by one parent (e.g., a balanced translocation), so parental chromosome testing is necessary.
• Pathophysiology: Loss of genes in the 18p region affects multiple pathways, including development, craniofacial formation, and endocrine, immune, and cardiac development, resulting in a variety of phenotypes.
• Main symptoms (frequency and severity vary among individuals):
  • Facial abnormalities: ptosis (drooping eyelids), strabismus, hypertelorism (eyes appearing widely spaced), large ears, micrognathia, and a large, drooping mouth
  • Neurodevelopment: intellectual disability (IQ reported to range from approximately 25–75), developmental delay, and microcephaly
  • Physical and medical abnormalities: growth impairment, congenital heart defects (possible), dental caries, immunoglobulin A (IgA) deficiency, and hair loss (baldness), among others
  • Other: Some individuals may have brain structural abnormalities (according to the provided data, holoprosencephaly in approximately 10%, etc.) and sex-chromosome-related manifestations (features resembling Turner syndrome).
• Prognosis: When there are no severe malformations or major organ abnormalities, many individuals survive into adulthood; however, the prognosis varies depending on symptoms and associated conditions.

Treatment Methods

• General principles: Because the chromosomal deletion cannot be reversed, treatment focuses on symptom-specific, multidisciplinary (medical genetics, pediatrics, pediatric cardiology, pediatric neurology, pediatric endocrinology, ophthalmology, otolaryngology, dentistry, rehabilitation medicine, etc.) support and conservative management.
• Main treatments and interventions:
  • Developmental and rehabilitation therapy: Early intervention (speech therapy, physical therapy, occupational therapy, and special education) — important for long-term prognosis
  • Heart defects: Diagnosis with echocardiography, followed by pediatric cardiac surgical treatment if necessary
  • Ophthalmic problems: Strabismus, ptosis, and other conditions are managed by ophthalmology with surgical correction or vision correction
  • Endocrinology: If there is growth delay and growth hormone deficiency is confirmed, growth hormone therapy may be considered (endocrine evaluation is necessary)
  • Immunity: In cases of IgA deficiency, infection management and, when necessary, immunologic evaluation and adjustment of the vaccination plan
  • Dentistry: Dental care and preventive treatment (cavity prevention)
  • Other: Depending on symptoms, ear and hearing tests, brain imaging and neurological management, mental health support, behavioral therapy, and other interventions
• Medications and surgery: Medications according to symptom management (e.g., anticonvulsants and antibiotics for infections) and surgery (cardiac surgery, facial surgery, etc.) are performed as needed.
• Lifestyle management and precautions:
  • Regular monitoring of growth and development, vaccinations, and prompt medical care when infections occur
  • Dental hygiene, vision and hearing management, and participation in educational and social support programs are recommended.
  • Genetic counseling and psychosocial support for parents and family members are recommended.

Checklist Before an Outpatient Visit (Including Example Questions)

• Items to prepare:
  • A list of currently used medications and supplements (including doses and administration times)
  • Previous test results (chromosome test reports, echocardiography, brain imaging, hormone tests, etc.)
  • Growth and developmental records (height and weight charts, developmental history), and vaccination records
  • Photos showing changes in symptoms (facial features, eye condition, etc.) or videos (showing how symptoms appear)
  • Family history: congenital abnormalities or a history of infertility or miscarriage in the parents, siblings, or other family members
• Important information to tell the doctor during the visit:
  • Recent infections or hospitalization history
  • Presence of seizures or suspicious symptoms
  • Eating and sleeping patterns and developmental progress
• Example questions (for the patient's caregiver):
  • “What are the results of the chromosome tests performed so far, and what do they mean?”
  • “How can we determine whether the child’s growth impairment is due to growth hormone deficiency?”
  • “What tests of the heart (or other organs) need to be performed, and by when?”

Examples of General Questions to Ask the Doctor

• “What is the cause of this condition, and what lesion (deletion location and extent) applies to my child?”
• “What developmental course and prognosis can be expected in the future?”
• “What regular tests are recommended (echocardiography, endocrine tests, hearing and vision tests, etc.), and how often should they be performed?”
• “What are the treatment options (nonsurgical/surgical) for the current symptoms, and what are their advantages and disadvantages?”
• “What is the risk of recurrence (the genetic risk in a subsequent pregnancy)? Is parental testing necessary?”

Examples of Condition-Specific Questions

• “Even though a balanced translocation was not identified in either parent’s chromosome test, what is the risk of recurrence? What parental genetic tests do you recommend?”
• “The child has growth delay. When and through what procedures should growth hormone deficiency testing be performed? What are the indications for treatment and the expected benefits?”

Additional recommendations:

• Once the diagnosis is confirmed, please receive genetic counseling in the medical genetics department to establish the parents’ recurrence risk, the need for family testing, and a long-term management plan.
• An initial evaluation by a multidisciplinary team (cardiology, ophthalmology, endocrinology, rehabilitation, dentistry, immunology, etc.) and regular follow-up are recommended.