Handbook of Genetic Counseling/Arthrogryposis

Arthrogryposis

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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: [1]

Email: info@avenuesforamc.com

NORD (National Organization of Rare Disorders)

Web: [2]

Arthrogryposis Multiplex Congenita Support Inc.

Web: [3]

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.