Handbook of Genetic Counseling/Arthrogryposis

Arthrogryposis

Contracting

• Acknowledge prior phone contact
• What questions or concerns would you like to address today?
• Overview of agenda for the session

Intake and Family History

• Pregnancy and medical history
  • Maternal fever or viruses during pregnancy?
  • Oligohydramnios or unusually shaped uterus? (Crumply ears, thin or hyperextensible skin?)
  • Was the baby active throughout the pregnancy?
  • Any problems with hands, wrists, elbows, shoulders, knees, jaw, or back?
  • Any muscle weakness or hypotonia?
  • Has she had any muscle biopsies or other blood tests to rule out possible disorders?
• Family history
  • Anyone else with club foot, joint dislocations, scoliosis?
  • Individuals who are short in stature?
  • Anyone with any muscular dystrophy, muscle disease, muscle weakness?
  • Anyone with cleft lip and/or palate, hearing loss, mental retardation?

Etiology

• Condition describing the presence of multiple joint contractures at birth
  • Joint contractures are limitations in the range of motion of joints
  • May affect few or all joints to varying degrees
    • Includes hands, wrists, elbows, shoulders, hips, feet, and knees
    • Severe cases may include the jaw and back
• Can be caused by anything that prevents normal joint movement before birth
  • When joint is not moved, extra connective tissue may grow around it and fix it in position
  • Tendons connecting to joint not stretched to normal length, making joint movement difficult
• Four possible reasons for limitation of joint movement prenatally
  • Muscles do not develop properly (atrophy)
    • Muscle diseases, including congenital muscular dystrophies
    • Maternal fever during pregnancy
    • Viruses that damage cells transmitting nerve impulses to muscle
  • There is not sufficient room in the uterus for normal movement
    • Oligohydramnios
    • Abnormally shaped uterus that causes crowding
  • Central nervous system or spinal cord malformations
  • Tendons, bones, joints, or joint linings don't develop properly
• May be environmental or genetic depending on cause of contractures
  • Genetic cause identified in about 30% of cases
  • Incidence is about 1 in 3000 live births

Causes of Arthrogryposis

• Diagnosis usually made by ruling out other causes or syndromes
• Cartilaginous abnormalities
  • Beal Syndrome
    • Linked to fibrillin locus on chromosome 5q23-31
    • Autosomal dominant
    • Crumpled ears, long slim limbs and fingers, frontal bossing, short neck
  • Antley-Bixer Syndrome
    • No confirmatory testing
    • Probably autosomal recessive
    • Crouzon syndrome-like appearance and midface hypoplasia
  • Distal Arthrogryposis Syndrome
    • Autosomal dominant with variable expression
    • Facial features usually normal
    • Arthrogryposis of hands and lesser extent feet
• Physical constraint to movement
  • Oligohydramnios Sequence
    • Diagnosis made by clinical findings
    • Arthrogryposis usually involves knees and feet
    • Wrinkled skin, squashed nose, low-set ears, short neck
    • Often secondary to bilateral renal agenesis
  • Escobar Syndrome
    • Autosomal recessive condition
    • Thick skin folds keep joints in fixed position
    • Restrict joint motility in neck, axilla, antecubital, popliteal, and digital areas
• Neurological Abnormalities
  • Trisomy 18 and Trisomy 13
    • Cause distal arthrogryposis
    • Causes severe mental retardation and facial dysmorphism
  • Smith-Lemli-Opitz
    • Autosomal recessive condition
    • Due to defect in cholesterol biosynthesis leading to severe MR and early death
    • Microcephaly, cryptorchidism, hypospadias, and arthrogryposis of hands
  • Zellweger Syndrome
    • Caused by genetic mutations at 7q11.23 and 1p22-21
    • Autosomal recessive inheritance
    • Severe hypotonia, brachycephaly, open fontanels, cryptorchidism, hypospadias, and distal arthrogryposis
  • Infantile Spinal Muscular Atrophy
    • Autosomal recessive and X-linked inheritance
    • Arthrogryposis occurs in 10-20% of neonates with SMA
  • Moebius Syndrome
    • Sporadic or autosomal dominant in some cases
    • Causes bilateral facial weakness and arthrogryposis in about 30% patients
  • Congenital Myotonic Dystrophy
    • Due to trinucleotide repeat expansion at 19q13
    • Autosomal dominant disorder
    • Marked body and facial hypotonia with arthrogryposis in lower extremities
  • Congenital Muscular Dystrophy
    • Inheritance pattern varies depending on type of muscular dystrophy
    • Hypotonia, muscle weakness, and distal arthrogryposis
    • Serum creatine kinase may be normal or elevated

Clinical Manifestations and Natural History

• Wide variation in degree to which muscles and joints are affected
  • May be accompanied by other conditions tat complicate the picture
  • Outlook is generally very positive
• Not a progressive condition
  • Substantial improvements seen with treatment
  • Most individuals are of normal intelligence and lead independent lives as adults
• Possible features
  • Head and neck
    • Facial asymmetry
    • Micrognathia, notched chin, or malar hypoplasia
    • Immobile facies
    • Low-set posteriorly located ears or overfolded helices
    • High nasal bridge
    • Highly arched palate, cleft lip, or cleft palate
    • Eyes
      • Keratoconus
      • Downslanting palpebral fissures
      • Blepharoptosis, hypertelorism, or ophthalmoplegia
      • Retinopathy
    • Short neck, fused cervical vertebrae, and pterygia
  • Chest deformities
  • Inguinal hernia
  • Hand and foot
    • • Overlapping fingers, tapered fingers, camptodactyly, or syndactyly
    • Clenched fists
    • Positional foot deformities or clubfoot
    • Single or bridged palmar creases
    • Absent or hypoplastic distal flexion creases
  • Extremities
    • Radial head dislocation, contractures, and limitation of motion
    • Affects shoulder, elbow, wrist, knee, ankle, and hip joints
  • Scoliosis and kyphosis
  • Microphallus and cryptorchidism
  • Elevated serum creatine phosphokinase
• Occasional growth and mental retardation

Treatment/Management

• First important to determine the cause
  • Influences prognosis, recurrence risk, and treatment
    • Definite diagnosis may not be possible in neonatal period
    • Important to separate neurological from non-neurological causes
  • MRI study for infants with neurological findings suggesting brain or spinal cord involvement
  • Chromosome analysis or genetic testing for those who appear to have genetic syndrome
• Physical therapy
  • Helps improve muscle strength and range of motion
  • Includes stretching, strengthening, mobility training, and training in ADL skills
• Casting or splinting
  • Splints can augment stretching to increase range of motion
  • Casting can improve foot position
  • Removable splint such as bi-valve cast or wearing splint at night often still allows motion and stretching
• Surgeries
  • Usually considered supportive measure to other forms of treatment
  • Performed on ankles to put feet in weight-bearing position
  • Tendon transfers can sometimes improve muscle function

Psychosocial Issues

• Parental concern over underlying cause of condition
• Reaction to infant requiring braces, casts, or surgeries
• Difficulty bonding with a child who looks different or requires special care
• Guilt, depression, anger over new diagnosis
• Concern for child's future

Support Resources

• National Support Group for Arthrogryposis

AVENUES

Web:

Email: info@avenuesforamc.com

• NORD (National Organization of Rare Disorders)

Web:

Arthrogryposis Multiplex Congenita Support Inc.

Web:

References

• Alfonson I, et al. "Arthrogryposis Multiplex Congenita." International Pediatrics (2000) 15:4;197-204.
• "Arthrogryposis Multiplex Congenita." Multiple Congenital Anomaly/Mental Retardation Syndromes: US National Library of Medicine. http://www.nlm.nih.gov
• "What is Arthrogryposis?" Published by AVENUES. http://www.avenuesforamc.com

Notes

The information in this outline was last updated in 2002.