Kniest dysplasia

Kniest dysplasia (Kniest dysplasia)

1) Disease Description (Causes and Symptoms)

• Causes and pathophysiology

  • Cause: It is mainly caused by variants due to heterozygous (hybrid) or point mutations in the COL2A1 (Type II collagen) gene, and the inheritance pattern is generally autosomal dominant. In many cases, the mutation is reported to be de novo.
  • Pathophysiology: Abnormalities in Type II collagen damage the structure and function of the cartilage matrix and growth plates, resulting in skeletal dysplasia. Tissues involving cartilage and connective tissue, such as the vitreous body and retina of the eye and structures of the middle ear, are also affected.

• Main symptoms

  • Body: Shortened trunk (short torso) and short stature, short neck, flat face (facial flattening), deformities of the clavicles, pelvis, femurs, and other bones (e.g., dumbbell-shaped femurs), joint stiffness and limited movement, delayed walking
  • Spine and chest: Platyspondyly, kyphotic and scoliotic deformities, possible vertical vertebral clefts during the neonatal period
  • Joints and soft tissue: Joint pain, enlargement or swelling of the soft tissues around the joints, early osteoarthritis
  • Ear and respiratory system: Chronic otitis media (hearing loss), tracheal cartilage softening (breathing difficulty and respiratory problems during infancy)
  • Ophthalmology: High myopia, risk of retinal degeneration and retinal detachment, cataracts, lens dislocation
  • Oral cavity: Cleft palate (harelip)
  • Other: Possible inguinal or umbilical hernia, small pelvis, findings of osteoporosis
  • Intelligence: Generally normal intelligence

2) Treatment Methods and Precautions

• Treatment principles

  • There is no specific treatment (therapeutic medication), and multidisciplinary, symptomatic management according to the symptoms is standard.
  • Team approach: Pediatrics/medical genetics, orthopedics, rehabilitation medicine/physical therapy, ophthalmology, otolaryngology (hearing), thoracic/respiratory care, oral and maxillofacial surgery, and others.

• Main treatment/management

  • Orthopedics: Spinal deformities (surgical correction and fusion in severe cases), orthopedic surgery of the hips, knees, and other areas (to improve function), physical therapy and rehabilitation to maintain joint range of motion
  • Pain management: Conservative treatment such as NSAIDs, and specialized pain treatment when necessary
  • Respiratory care: Oxygen and airway management for respiratory distress during infancy, and specialized treatment for severe airway problems
  • Otolaryngology: Insertion of tympanostomy tubes for chronic otitis media, hearing aids and auditory rehabilitation
  • Ophthalmology: Regular retinal examinations, emergency surgery in the event of retinal detachment (such as vitrectomy), vision correction
  • Cleft palate: Palate surgery and speech therapy
  • Genetic counseling: Pedigree construction, testing of parents and family members, and counseling about molecular genetic testing during pregnancy (fetal genetic testing/PGD)

• Lifestyle management and precautions

  • Avoid excessive use of the joints and impact, and reduce the load on the joints through weight management
  • Maintain joint range of motion and strengthen muscles through regular physical therapy
  • Have vision or hearing abnormalities evaluated immediately (retinal detachment is an emergency)
  • Management of and vaccination against infections such as otitis media are recommended (to prevent respiratory complications)
  • Be alert for infection and respiratory complications after surgery

• Risk of complications

  • Early osteoarthritis, blindness due to retinal detachment, progressive hearing loss, neurological symptoms or breathing difficulty due to severe spinal deformity

3) Checklist Before an Outpatient Visit (Items to Prepare and Example Questions)

• Items to bring (recommended)

  • List of current medications and supplements (including doses and administration times)
  • Records of previous surgeries and hospitalizations, and anesthesia records (copies if possible)
  • Previous test results (genetic tests, X-rays, MRI, and ophthalmology and otolaryngology findings)
  • Growth chart (records of changes in height and weight), and notes on when symptoms began and their progression
  • Family history (family members with similar symptoms and whether relatives have been diagnosed)
  • Photographs (full body, face, chest, limbs, etc.) — useful when the doctor evaluates external changes

• Key information to tell the doctor during the outpatient visit

  • When symptoms began and how they have progressed (breathing difficulty, pain, decreased vision, etc.)
  • Recent history of infections, surgery, or hospitalization, and the degree of activity limitation (whether the person walks and whether walking aids are used)
  • Pregnancy plans or current pregnancy status (related to genetic counseling)

4) Examples of General Questions to Ask the Doctor

• What are the side effects and precautions for this medication (or treatment)?
• What is the expected prognosis for me (or my child)? What should be managed as a priority for quality of life?
• What points should be considered regarding lifestyle habits such as exercise and school activities?
• Which items should be included in regular checkups (ophthalmology, otology, orthopedics, etc.), and how often should they be performed?
• What are the genetic risks and available testing options before or during pregnancy and childbirth?

5) Examples of Disease-Specific Questions

• If a COL2A1 genetic variant has been confirmed, what is the probability of inheritance by children (autosomal dominant), and what is the recommended scope of family testing?
• To reduce the risk of retinal detachment, at what intervals should regular ophthalmologic examinations be performed, and what immediate action should be taken if changes in vision (e.g., flashes, black spots, or visual field defects) occur?

(When necessary, referral to each relevant specialty and scheduling a session for interpretation of genetic test results and genetic counseling are recommended.)