Abstract
Purpose
Fetal akinesia deformation sequence (FADS) is a clinically and genetically heterogenous disorder. In this study, the different sonographic abnormalities are described in a larger number of affected fetuses.
Methods
This retrospective study included 79 cases of suspected FADS observed in our tertiary referral center between January 2001 and February 2015. Electronic stored reports and images of the examination were reviewed as well as autopsy reports and pediatric charts.
Results
In the study population (mean gestational age 23 + 4 weeks) consanguinity, multiple miscarriages or positive family history were present in 31.6 % of cases. Abnormalities of the facial profile (58.3 %) and ankle joint (83.6 %) were detected in the majority of cases. Contractures variably involved knee-, ankle-, wrist- and elbow joint and fingers with no distinct patterns. Additional malformations, most commonly of the brain, were found in 44.3 % of cases. Diagnosis before 20 weeks was associated with nuchal edema in 62.5 and hydrops in 31.3 %. In fetuses evaluated later than 24 weeks, IUGR, increased amniotic fluid or thorax hypoplasia were diagnosed, in 31, 58.8 and 37.9 %, respectively. Termination of pregnancy was requested in 86.1 %, 11 (13.9 %) children were live born. No underlying genetic cause was established, but in one asymptomatic mother myasthenia gravis was revealed.
Conclusions
Fetal akinesia presents with heterogeneous sonographic findings, mostly affecting the profile, elbow-, knee-, ankle joint, wrists and fingers; in most of cases of sporadic nature. Whereas hydrops fetalis and nuchal edema were earlier signs, thorax hypoplasia, polyhydramnios and IUGR were found later in pregnancy.
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References
Moessinger AC (1983) Fetal akinesia deformation sequence: an animal model. Pediatrics 72:857–863
Hall JG (1986) Diagnostic approaches and prognosis in arthrogryposis (congenital contractures). Pathologica 78:701–708
Pena SD, Shokeir MH (1974) Syndrome of camptodactyly, multiple ankyloses, facial anomalies, and pulmonary hypoplasia: a lethal condition. J Pediatr 85:373–375
Hall JG (2014) Arthrogryposis (multiple congenital contractures): diagnostic approach to etiology, classification, genetics, and general principles. Eur J Med Genet 57:464–472
Kalampokas E, Kalampokas T, Sofoudis C et al (2012) Diagnosing arthrogryposis multiplex congenita: a review. ISRN Obstet Gynecol 2012:264918
Ravenscroft G, Sollis E, Charles AK et al (2011) Fetal akinesia: review of the genetics of the neuromuscular causes. J Med Genet 48:793–801
Hoellen F, Schroer A, Kelling K et al (2011) Arthrogryposis multiplex congenita and Pena–Shokeir phenotype: challenge of prenatal diagnosis—report of 21 cases, antenatal findings and review. Fetal Diagn Ther 30:289–298
Dane B, Dane C, Aksoy F et al (2009) Arthrogryposis multiplex congenita: analysis of twelve cases. Clin Exp Obstet Gynecol 36:259–262
Hyett J, Noble P, Sebire NJ et al (1997) Lethal congenital arthrogryposis presents with increased nuchal translucency at 10–14 weeks of gestation. Ultrasound Obstet Gynecol 9:310–313
Paladini D, Tartaglione A, Agangi A et al (2001) Pena–Shokeir phenotype with variable onset in three consecutive pregnancies. Ultrasound Obstet Gynecol 17:163–165
Witters I, Moerman P, Fryns JP (2002) Fetal akinesia deformation sequence: a study of 30 consecutive in utero diagnoses. Am J Med Genet 113:23–28
Rink BD (2011) Arthrogryposis: a review and approach to prenatal diagnosis. Obstet Gynecol Surv 66:369–377
Michalk A, Stricker S, Becker J et al (2008) Acetylcholine receptor pathway mutations explain various fetal akinesia deformation sequence disorders. Am J Hum Genet 82:464–476
Hoffmann K, Muller JS, Stricker S et al (2006) Escobar syndrome is a prenatal myasthenia caused by disruption of the acetylcholine receptor fetal gamma subunit. Am J Hum Genet 79:303–312
Vogt J, Morgan NV, Rehal P et al (2012) CHRNG genotype-phenotype correlations in the multiple pterygium syndromes. J Med Genet 49:21–26
Chen CP (2012) Prenatal diagnosis and genetic analysis of fetal akinesia deformation sequence and multiple pterygium syndrome associated with neuromuscular junction disorders: a review. Taiwan J Obstet Gynecol 51:12–17
McKie AB, Alsaedi A, Vogt J et al (2014) Germline mutations in RYR1 are associated with foetal akinesia deformation sequence/lethal multiple pterygium syndrome. Acta Neuropathol Commun 2:148
Vogt J, Morgan NV, Marton T et al (2009) Germline mutation in DOK7 associated with fetal akinesia deformation sequence. J Med Genet 46:338–340
Tan-Sindhunata MB, Mathijssen IB, Smit M et al (2015) Identification of a Dutch founder mutation in MUSK causing fetal akinesia deformation sequence. Eur J Hum Genet 23:1151–1157
Wilbe M, Ekvall S, Eurenius K et al (2015) MuSK: a new target for lethal fetal akinesia deformation sequence (FADS). J Med Genet 52:195–202
Monnier N, Lunardi J, Marty I et al (2009) Absence of beta-tropomyosin is a new cause of Escobar syndrome associated with nemaline myopathy. Neuromuscul Disord 19:118–123
Polizzi A, Huson SM, Vincent A (2000) Teratogen update: maternal myasthenia gravis as a cause of congenital arthrogryposis. Teratology 62:332–341
Hoff JM, Daltveit AK, Gilhus NE (2006) Artrogryposis multiplex congenita—rare fetal condition caused by maternal myasthenia gravis. Acta Neurol Scand Suppl 183:26–27
Dalton P, Clover L, Wallerstein R et al (2006) Fetal arthrogryposis and maternal serum antibodies. Neuromuscul Disord 16:481–491
Hall JG (2013) Uterine structural anomalies and arthrogryposis-death of an urban legend. Am J Med Genet A 161A:82–88
Mayumi M, Obata-Yasuoka M, Ogura T et al (2013) Discordance in Pena–Shokeir phenotype/fetal akinesia deformation sequence in a monoamniotic twin. J Obstet Gynaecol Res 39:344–346
Ho NC (2000) Monozygotic twins with fetal akinesia: the importance of clinicopathological work-up in predicting risks of recurrence. Neuropediatrics 31:252–256
Perlman JM, Burns DK, Twickler DM et al (1995) Fetal hypokinesia syndrome in the monochorionic pair of a triplet pregnancy secondary to severe disruptive cerebral injury. Pediatrics 96:521–523
Hall JG (1986) Analysis of Pena Shokeir phenotype. Am J Med Genet 25:99–117
Senocak EU, Oguz KK, Haliloglu G et al (2009) Prenatal diagnosis of Pena–Shokeir syndrome phenotype by ultrasonography and MR imaging. Pediatr Radiol 39:377–380
Santana EF, Oliveira Serni PN, Rolo LC et al (2014) Prenatal Diagnosis of Arthrogryposis as a Phenotype of Pena–Shokeir Syndrome using Two- and Three-dimensional Ultrasonography. J Clin Imaging Sci 4:20
Zaki M, Boyd PA, Impey L et al (2007) Congenital myotonic dystrophy: prenatal ultrasound findings and pregnancy outcome. Ultrasound Obstet Gynecol 29:284–288
Hall JG, Aldinger KA, Tanaka KI (2014) Amyoplasia revisited. Am J Med Genet A 164A:700–730
Farwell KD, Shahmirzadi L, El-Khechen D et al (2015) Enhanced utility of family-centered diagnostic exome sequencing with inheritance model-based analysis: results from 500 unselected families with undiagnosed genetic conditions. Genet Med 17:578–586
Alamillo CL, Powis Z, Farwell K et al. (2015) Exome sequencing positively identified relevant alterations in more than half of cases with an indication of prenatal ultrasound anomalies. Prenat Diagn 35:1073–1078
Volk A, Conboy E, Wical B et al (2015) Whole-exome sequencing in the clinic: lessons from six consecutive cases from the clinician’s perspective. Mol Syndromol 6:23–31
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This is a retrospective study of data routinely achieved and anonymously analyzed in accordance to our local ethics committee. Otherwise the manuscript does not contain clinical studies or patient data.
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Hellmund, A., Berg, C., Geipel, A. et al. Prenatal diagnosis of fetal akinesia deformation sequence (FADS): a study of 79 consecutive cases. Arch Gynecol Obstet 294, 697–707 (2016). https://doi.org/10.1007/s00404-016-4017-x
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DOI: https://doi.org/10.1007/s00404-016-4017-x