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.