Advertisement

Arthrogryposis

      Introduction

      Arthrogryposis or arthrogryposis multiplex congenita describes joint contractures in two or more areas of the body and is present in 1 in 3000 live births.
      • Hall J.
      Arthrogryposis.
      It is usually a feature of abnormal neurologic development or primary muscular disorders of the fetus. More than 400 conditions are associated with this finding, which makes a specific prenatal diagnosis challenging.
      • Hall J.G.
      Arthrogryposis (multiple congenital contractures): diagnostic approach to etiology, classification, genetics, and general principles.

      Definition

      Fetal arthrogryposis detected with prenatal ultrasound imaging is defined as ≥2 joint contractures in >1 body area. Arthrogryposis is not a specific diagnosis but rather is a descriptive term for multiple contractures that can be associated with many different medical conditions.

      Ultrasound Findings

      Arthrogryposis is a clinical finding caused by a lack of fetal movement (fetal akinesia). The severity of arthrogryposis is related directly to the duration of decreased fetal movement. Characteristic ultrasound findings include flexion abnormalities of both the proximal and distal joints (Figure 1); these are usually seen with decreased or absent movement of the affected extremity. In addition to the extremities, the jaw, spine, and fetal neck can also be involved; attention should be paid to the mobility of these joints as well.
      • Rink B.D.
      Arthrogryposis: a review and approach to prenatal diagnosis.
      Hypomineralization of the long bones has been reported.
      • Murphy J.C.
      • Neale D.
      • Bromley B.
      • Benacerraf B.R.
      • Copel J.A.
      Hypoechogenicity of fetal long bones: a new ultrasound marker for arthrogryposis.
      Joint contractures usually do not become evident until the second trimester. First-trimester ultrasound findings can include increased nuchal translucency and cystic hygroma.
      • Hyett J.
      • Noble P.
      • Sebire N.J.
      • Snijders R.
      • Nicolaides K.H.
      Lethal congenital arthrogryposis presents with increased nuchal translucency at 10-14 weeks of gestation.
      ,
      • Scott H.
      • Hunter A.
      • Bedard B.
      Non-lethal arthrogryposis multiplex congenita presenting with cystic hygroma at 13 weeks gestational age.
      Figure thumbnail gr1
      Figure 1Arthrogryposis
      Two-dimensional ultrasound image shows hyperextension or “pike” position of lower limbs.
      SMFM Fetal Anomalies Consult Series #2. Am J Obstet Gynecol 2019.
      A high index of suspicion is necessary because the diagnosis of arthrogryposis is difficult. In one series, almost 75% of cases were missed on prenatal ultrasound imaging.
      • Hall J.G.
      Arthrogryposis (multiple congenital contractures): diagnostic approach to etiology, classification, genetics, and general principles.
      ,
      • Filges I.
      • Hall J.G.
      Failure to identify antenatal multiple congenital contractures and fetal akinesia: proposal of guidelines to improve diagnosis.
      When arthrogryposis is suspected, a detailed ultrasound examination should be performed to detect other abnormalities that may give insight into the underlying cause and guide patient counseling. Three-dimensional ultrasound imaging sometimes can provide more detailed information about the affected extremity
      • Lin I.W.
      • Chueh H.Y.
      • Chang S.D.
      • Cheng P.J.
      The application of three-dimensional ultrasonography in the prenatal diagnosis of arthrogryposis.
      (Figure 2). With multiple abnormalities, especially if central nervous system abnormalities are suspected, magnetic resonance imaging may provide additional information regarding prognosis.
      • Rink B.D.
      Arthrogryposis: a review and approach to prenatal diagnosis.
      ,
      • Skaria P.
      • Dahl A.
      • Ahmed A.
      Arthrogryposis multiplex congenita in utero: radiologic and pathologic findings.
      Figure thumbnail gr2
      Figure 2Three-dimensional ultrasound imaging
      These three-dimensional images show the position of joints. A, The fetal right foot is angled acutely inward compared to the fetal right leg. B, The cross-legged “tailor’s position” of lower limbs and feet.
      SMFM Fetal Anomalies Consult Series #2. Am J Obstet Gynecol 2019.

      Associated Abnormalities

      Abnormalities in every organ system have been reported in association with arthrogryposis. An increased nuchal translucency and cystic hygroma have been reported in the first trimester and may indicate lethal forms of arthrogryposis.
      • Hyett J.
      • Noble P.
      • Sebire N.J.
      • Snijders R.
      • Nicolaides K.H.
      Lethal congenital arthrogryposis presents with increased nuchal translucency at 10-14 weeks of gestation.
      ,
      • Scott H.
      • Hunter A.
      • Bedard B.
      Non-lethal arthrogryposis multiplex congenita presenting with cystic hygroma at 13 weeks gestational age.
      Central nervous system abnormalities that have been reported with arthrogryposis include cerebral and cerebellar hypoplasia, ventriculomegaly, and holoprosencephaly.
      • Fedrizzi E.
      • Botteon G.
      • Inverno M.
      • Ciceri E.
      • D’Incerti L.
      • Dworzak F.
      Neurogenic arthrogryposis multiplex congenita: clinical and MRI findings.
      Gastroschisis and bowel atresia can be seen in primary myopathies. Polyhydramnios is often present and results from decreased fetal swallowing.
      • Rink B.D.
      Arthrogryposis: a review and approach to prenatal diagnosis.
      Micrognathia, cleft palate, hypertelorism, fetal growth restriction, pulmonary hypoplasia, and mildly shortened long bones comprise the phenotype known as fetal akinesia sequence or Pena-Shokeir phenotype.
      • Hall J.G.
      Pena-Shokeir phenotype (fetal akinesia deformation sequence) revisited.
      Osteoporosis from lack of fetal movement occurs most frequently in the fetal long bones and can predispose to fractures, usually at the time of delivery.
      • Rink B.D.
      Arthrogryposis: a review and approach to prenatal diagnosis.

      Differential Diagnosis

      The differential diagnosis of arthrogryposis is extensive. More than 400 conditions are characterized by this finding, and the features and severity can vary dramatically.
      • Hall J.G.
      Arthrogryposis (multiple congenital contractures): diagnostic approach to etiology, classification, genetics, and general principles.
      Genetic patterns of inheritance vary from single-gene disorders to chromosomal abnormalities, such as trisomy 18.
      • Hall J.G.
      • Kiefer J.
      Arthrogryposis as a syndrome: gene ontology analysis.
      Arthrogryposis may be inherited as an autosomal recessive, autosomal dominant, or X-linked trait, and some cases are thought to have multifactorial inheritance, with both genetic and environmental factors. Maternal infections (eg, rubella, Zika, and Coxsackievirus) and environmental factors have also been associated with arthrogryposis; therefore, obtaining a history of maternal exposures and a family history is important.
      • Fahy M.J.
      • Hall J.G.
      A retrospective study of pregnancy complications among 828 cases of arthrogryposis.
      Witters et al. reported a specific diagnosis in only 53% of cases using prenatal information and fetopathologic specimens.
      • Witters I.
      • Moerman P.
      • Fryns J.P.
      Fetal akinesia deformation sequence: a study of 30 consecutive in utero diagnoses.

      Genetic Evaluation

      Genetic variants, duplications, deletions, and chromosomal abnormalities are found in approximately 30% of cases of arthrogryposis.
      • Skaria P.
      • Dahl A.
      • Ahmed A.
      Arthrogryposis multiplex congenita in utero: radiologic and pathologic findings.
      Diagnostic testing (amniocentesis or chorionic villus sampling) with chromosomal microarray analysis (CMA) should be offered when arthrogryposis is detected.
      American College of Obstetricians and Gynecologists
      Practice Bulletin No. 162: Prenatal diagnostic testing for genetic disorders.
      Karyotype analysis or fluorescence in situ hybridization with reflex to CMA may be reasonable if a common aneuploidy is suspected. Gene panel testing or exome sequencing may be useful because CMA does not detect single-gene (Mendelian) disorders; more than 350 gene variants have been reported to cause different types of arthrogryposis. Testing for spinal muscular atrophy and congenital myotonic dystrophy in particular should be considered. If exome sequencing is pursued, appropriate pretest and posttest genetic counseling by a provider experienced in the complexities of genomic sequencing is recommended.
      International Society for Prenatal Diagnosis, Society for Maternal Fetal Medicine, Perinatal Quality Foundation
      Joint position statement from the International Society for Prenatal Diagnosis (ISPD), the Society for Maternal Fetal Medicine (SMFM), and the Perinatal Quality Foundation (PQF) on the use of genome-wide sequencing for fetal diagnosis.
      If the pregnancy ends in a stillbirth or neonatal death, an autopsy should be offered. After appropriate counseling, cell-free DNA screening is an option for patients who decline diagnostic testing, although it is likely to have a low diagnostic yield because aneuploidy causes only a small number of cases.

      Pregnancy and Delivery Management

      A detailed ultrasound examination should be performed and should include comprehensive imaging of the intracranial structures (eg, a neurosonogram) and the fetal heart. A fetal echocardiogram and fetal magnetic resonance imaging to assess for intracranial abnormalities should be considered if cardiac or central nervous system abnormalities are suspected or with other clinical indications (eg, enlarged nuchal translucency). Testing for maternal viral infections should be considered, including rubella, Zika, and Coxsackievirus, if risk factors are present. Referrals to pediatric neurology, orthopedics, and neonatology should be considered. Pregnancy termination is an option that should be discussed with all patients in whom a fetal anomaly is detected. Shared patient decision-making requires thorough evaluation and multidisciplinary counseling regarding prognosis. The specific finding of arthrogryposis generally does not affect delivery management, although delivery at a tertiary care center with pediatric genetics, neurology, and orthopedic consultation may be considered to be appropriate for the clinical findings. If the jaw or cervical spine is suspected to be involved, a multidisciplinary approach and the involvement of neonatology, anesthesiology, and potentially otolaryngology services to assure airway access at birth may be required.

      Prognosis

      The prognosis of arthrogryposis depends on the underlying cause, the extent of the contractures, and associated abnormalities. In some cases, the contractures can improve with postnatal treatment, and early physiotherapy and orthopedic intervention are recommended to help with joint motility. Some infants who are born with arthrogryposis will have a good outcome, although the prognosis is dependent on the underlying cause.

      Summary

      Arthrogryposis or arthrogryposis multiplex congenita is defined as ≥2 joint contractures in >1 body area and is present in 1 in 3000 live births.
      • Hall J.
      Arthrogryposis.
      It is usually a marker for abnormal neurologic development or primary muscular disorders of the fetus. When suspected, a detailed ultrasound examination should be performed to detect other abnormalities that may give insight into the underlying cause and guide patient counseling. Because more than 400 conditions are associated with this finding,
      • Hall J.G.
      Arthrogryposis (multiple congenital contractures): diagnostic approach to etiology, classification, genetics, and general principles.
      genetic counseling should be offered. Mode of delivery should be based on usual obstetric indications. The prognosis will depend on the underlying cause; however, with the appropriate physiotherapy and orthopedic intervention, many infants with isolated arthrogryposis have a good outcome.

      References

        • Hall J.
        Arthrogryposis.
        in: Cassidy S. Allanson J. Management of genetic syndromes. 2nd ed. Wiley & Sons, Hoboken (NJ)2005: 63-75
        • Hall J.G.
        Arthrogryposis (multiple congenital contractures): diagnostic approach to etiology, classification, genetics, and general principles.
        Eur J Med Genet. 2014; 57: 464-472
        • Rink B.D.
        Arthrogryposis: a review and approach to prenatal diagnosis.
        Obstet Gynecol Surv. 2011; 66: 369-377
        • Murphy J.C.
        • Neale D.
        • Bromley B.
        • Benacerraf B.R.
        • Copel J.A.
        Hypoechogenicity of fetal long bones: a new ultrasound marker for arthrogryposis.
        Prenat Diagn. 2002; 22: 1219-1222
        • Hyett J.
        • Noble P.
        • Sebire N.J.
        • Snijders R.
        • Nicolaides K.H.
        Lethal congenital arthrogryposis presents with increased nuchal translucency at 10-14 weeks of gestation.
        Ultrasound Obstet Gynecol. 1997; 9: 310-313
        • Scott H.
        • Hunter A.
        • Bedard B.
        Non-lethal arthrogryposis multiplex congenita presenting with cystic hygroma at 13 weeks gestational age.
        Prenat Diagn. 1999; 19: 966-971
        • Filges I.
        • Hall J.G.
        Failure to identify antenatal multiple congenital contractures and fetal akinesia: proposal of guidelines to improve diagnosis.
        Prenat Diagn. 2013; 33: 61-74
        • Lin I.W.
        • Chueh H.Y.
        • Chang S.D.
        • Cheng P.J.
        The application of three-dimensional ultrasonography in the prenatal diagnosis of arthrogryposis.
        Taiwan J Obstet Gynecol. 2008; 47: 75-78
        • Skaria P.
        • Dahl A.
        • Ahmed A.
        Arthrogryposis multiplex congenita in utero: radiologic and pathologic findings.
        J Matern Fetal Neonatal Med. 2019; 32: 502-511
        • Fedrizzi E.
        • Botteon G.
        • Inverno M.
        • Ciceri E.
        • D’Incerti L.
        • Dworzak F.
        Neurogenic arthrogryposis multiplex congenita: clinical and MRI findings.
        Pediatr Neurol. 1993; 9: 343-348
        • Hall J.G.
        Pena-Shokeir phenotype (fetal akinesia deformation sequence) revisited.
        Birth Defects Res A Clin Mol Teratol. 2009; 85: 677-694
        • Hall J.G.
        • Kiefer J.
        Arthrogryposis as a syndrome: gene ontology analysis.
        Mol Syndromol. 2016; 7: 101-109
        • Fahy M.J.
        • Hall J.G.
        A retrospective study of pregnancy complications among 828 cases of arthrogryposis.
        Genet Couns. 1990; 1: 3-11
        • Witters I.
        • Moerman P.
        • Fryns J.P.
        Fetal akinesia deformation sequence: a study of 30 consecutive in utero diagnoses.
        Am J Med Genet. 2002; 113: 23-28
        • American College of Obstetricians and Gynecologists
        Practice Bulletin No. 162: Prenatal diagnostic testing for genetic disorders.
        Obstet Gynecol. 2016; 127: e108-e122
        • International Society for Prenatal Diagnosis, Society for Maternal Fetal Medicine, Perinatal Quality Foundation
        Joint position statement from the International Society for Prenatal Diagnosis (ISPD), the Society for Maternal Fetal Medicine (SMFM), and the Perinatal Quality Foundation (PQF) on the use of genome-wide sequencing for fetal diagnosis.
        Prenat Diagn. 2018; 38: 6-9