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
 * Phone: 209-928-3688
 * Web:
 * Email: avenues@sonnet.com


 * NORD (National Organization of Rare Disorders)
 * Web: