Arthrogryposis Multiplex Congenita and Pena-Shokeir Phenotype: Challenge of Prenatal Diagnosis – Report of 21 Cases, Antenatal Findings and Review

Abstract

Objective: To elaborate the antenatal sonographic findings of fetuses with the suspicion of fetal akinesia, thereby focusing on the accuracy of prenatal differentiation between subtypes of fetal akinesia, namely Pena-Shokeir phenotype (PSP) and arthrogryposis multiplex congenita (AMC). Methods: We herein present our experience of 21 patients with PSP and AMC diagnosed antenatally at a tertiary prenatal referral center. During the study period 30,485 consecutive high- and low-risk pregnancies were examined. The prenatal sonograms, pediatric charts and autopsy data of affected individuals were reviewed. Our findings were analyzed together with findings retrieved from the literature. Results: The diagnosis of AMC has been established between 12+0 and 30+1 gestational weeks, whereas cases found to have PSP were all diagnosed in advanced pregnancy. In accordance to previous findings, our data suggest that pulmonary hypoplasia is obligatory in PSP and cannot be found in AMC. Therefore, all pregnancies (9/9) affected by PSP were terminated on parental request. Of those fetuses with AMC, 3/12 were liveborn, 2 of which have neuromotoric disabilities. Conclusions: Establishing the correct prenatal diagnosis of PSP and AMC at an early stage and its diligent prognostic evaluation play a crucial role in order to provide adequate advice to the afflicted parents and to enable appropriate intervention at an early stage.

Failure to identify antenatal multiple congenital contractures and fetal akinesia – proposal of guidelines to improve diagnosis

“…Antenatally or perinatally, lethal disorders mostly manifest early in pregnancy from the first trimester onwards. Lethal forms show early lung hypoplasia (and later thoracic hypoplasia), or pterygia . Reduced fetal breathing may be observed.…”

“…Genes encoding skeletal muscle proteins, involved in tissue and structural development and differentiation as well as contraction processes [58][59][60][61] or pterygia. 62 Reduced fetal breathing may be observed.…”

Fetal akinesia deformation sequence, arthrogryposis multiplex congenita, and bilateral clubfeet: Is motor assessment of additional value for in utero diagnosis? A 10‐year cohort study

“…Most of our cases did not show these latter features since the pregnancy was often terminated before 24 weeks of gestation. The second case series on antenatal findings in 21 cases with AMC and FADS examined between 12–30 weeks gestational age suggested that pulmonary hypoplasia is obligatory in FADS and cannot be found in AMC . When pulmonary hypoplasia was found, the pregnancy was terminated.…”

“…However, the limited serial motor assessments demonstrated which reduced activity, is a late expression of affected motor activity and possibly not initiating the contractures . Though different authors advise evaluation of the fetal motility, until now, the main focus has been on diagnosing the different structural anomalies known to occur with FADS …”

“…Prenatal detection of the phenotype fetal akinesia deformation sequence (FADS) through ultrasound examination has been reported as early as the first trimester of pregnancy, but also during the third trimester with varied expressions, making diagnosis challenging . Arthrogryposis multiplex congenita (multiple contractures in various regions, AMC) including FADS was missed in 73.8% during prenatal ultrasound examination in 107 cases with neonatal confirmed arthrogryosis …”