Prenatal diagnosis and genetic analysis of fetal akinesia deformation sequence and multiple pterygium syndrome associated with neuromuscular junction disorders: A review

Abstract

Fetal akinesia deformation sequence is a clinically and genetically heterogeneous disorder characterized by a variable combination of arthrogryposis, fetal akinesia, intrauterine growth restriction, developmental abnormalities such as cystic hygroma, pulmonary hypoplasia, cleft palate, cryptorchidism, cardiac defects and intestinal malrotation, and occasional pterygia of the limbs. Multiple pterygium syndrome is a clinically and genetically heterogeneous disorder characterized by pterygia of the neck, elbows and/or knees, arthrogryposis, and other phenotypic features such as short stature, genital abnormalities, craniofacial abnormalities, clubfoot, kyphoscoliosis, and cardiac abnormalities. Fetal akinesia deformation sequence may phenotypically overlap with the lethal type of multiple pterygium syndrome. This article provides a comprehensive review of prenatal diagnosis and genetic analysis of fetal akinesia deformation sequence and multiple pterygium syndrome associated with neuromuscular junction disorders. Prenatal diagnosis of fetal akinesia along with cystic hygroma, increased nuchal translucency, nuchal edema, hydrops fetalis, arthrogryposis, pterygia, and other structural abnormalities should include a differential diagnosis of neuromuscular junction disorders. Genetic analysis of mutations in the neuromuscular junction genes such as CHRNA1, CHRND, CHRNG, CNTN1, DOK7, RAPSN, and SYNE1 may unveil the pathogenetic cause of fetal akinesia deformation sequence and multiple pterygium syndrome, and the information acquired is helpful for genetic counseling and clinical management.

Lethal multiple pterygium syndrome

“…[1] The lethal form of MPS (OMIM 253290) has a wide clinical spectrum of malformations such as webbing of skin (pterygia) of elbow, knee, neck, cystic hygroma, cleft lip/palate, rocker bottom feet deformity, pulmonary hypoplasia, cryptorchidism, joint contractures, fetal akinesia, cardiac defects, kyphoscoliosis, fetal growth restriction, and intestinal malrotation. [12] The mode of inheritance can be either autosomal recessive, autosomal dominant, or X-linked dominant. [1] The exact etiology is unknown, but the condition has an association with embryonic acetylcholine receptor mutations.…”

“…[12] The mode of inheritance can be either autosomal recessive, autosomal dominant, or X-linked dominant. [1] The exact etiology is unknown, but the condition has an association with embryonic acetylcholine receptor mutations. The genes of embryonic acetylcholine receptors are CHRNA1 (OMIM 100690), CHRND (OMIM 100720), CHRNG (OMIM 100730), RAPSN (OMIM 601592), DOK7 (OMIM 610285), CNTN1 (OMIM 600016), and SYNE1 (OMIM 608441) located on long arm of chromosome 2.…”

Analysis of musculoskeletal dysmorphic abnormalities of 20 fetuses

“…One fetus had lethal multiple pterygium syndrome, [12] which has been reported as characterized by intrauterine growth restriction and pterygia in multiple areas (chin to sternum, cervical, axillary, humeroulnar, crural, popliteal, and the ankles) and flexion contractures giving rise to severe arthrogryposis. The fetus in our series was diagnosed with intrauterine growth restriction and multiple pterygium areas (cervical, axillary, humeroulnar, popliteal and ankles) (Figure 7).…”

Prenatal Diagnosis of Arthrogryposis as a Phenotype of Pena-Shokeir Syndrome using Two- and Three-dimensional Ultrasonography

“…[1] Limb contracture and the process of muscle atrophy result from lack of adequate movement. [6] Lung development stagnates around the 15 th week of pregnancy, in the canalicular phase, in which there is development of pulmonary hypoplasia in the diminished thoracic cavity. This occurs due to the absence of adequate development of the diaphragm and intercostal muscles, since these do not perform early respiratory movements.…”

“…The decreased fetal swallowing results in polyhydramnios and the underdevelopment of facial muscles explains the craniofacial defects. [6]…”