# 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.