Lahtela et al. (2010) described a Finnish family in which 5 pregnancies occurred. The parents were healthy, and their first pregnancy ended in a first-trimester miscarriage. In the second and third pregnancies, ultrasonography revealed multiple malformations of the ... Lahtela et al. (2010) described a Finnish family in which 5 pregnancies occurred. The parents were healthy, and their first pregnancy ended in a first-trimester miscarriage. In the second and third pregnancies, ultrasonography revealed multiple malformations of the fetuses at 13 and 12 weeks' gestation, respectively. These pregnancies were terminated at 14 and 13 weeks, respectively. The fourth and fifth pregnancies resulted in the births of normal infants. Samples were available from the parents and the 2 affected fetuses. At ultrasound, both fetus 1 and fetus 2 had an abnormal cyst in the cranial region, a large defect of the craniofacial area, and an omphalocele, as well as immotile and hypoplastic limbs. Autopsy of fetus 1 revealed a defect in the diaphragm, tetralogy of Fallot, and a horseshoe kidney. The skull bones were underdeveloped, and there was lobulation defect in both lungs, with 4 lobes on the right and 3 on the left. All the bones that were visible were hypoplastic but normal in number and configuration. Fetus 2 had 3 lung lobes in each lung; the other inner organs appeared normal. The skeletal muscles of both fetuses were very poorly developed, probably because of lack of movement. Bone structure revealed a normal growth plate with features of chondrodystrophy. Skin sections of the limbs were very thin, with only 2 to 5 layers of epidermal cells. The structure resembled a membrane. There was no basal hyperplasia. The stratum granulosum and horny layer were absent; however, both fetuses were below the age at which keratinization of the epidermis occurs. Skin on the outer aspects of the limbs had no adnexal structures, although some primitive hair follicles were seen. There was an island of squamous epithelium within the bony structures of the head, probably representing an unopened mouth. Based on Finnish genealogic analysis, Lahtela et al. (2010) concluded that the parents shared a common ancestor who lived in the eighteenth century. Lahtela et al. (2010) pointed to the case reported by Stevenson et al. (1987), described as a 'cocoon fetus' with a similar encasement malformation. The general appearance of the fetus, born at 27 weeks' gestation, was most striking, with microcephaly, absent pinnae, protruding optic globes and conjunctivae, gaping mouth with protruding tongue, absent mandible, folding and fusion of all parts of the extremities to the trunk, and absent external genitalia. Pathologic examination revealed normal thoracic and abdominal viscera with intraabdominal testes. Skin from the scalp and buttocks histologically showed thinned dermis with absence of sweat glands and hair follicles, and thinned epidermis with hyperkeratosis, large keratohyaline granules in the granular layer, and absence of rete ridges. Epidermis and dermis were separated in all sections examined.
Lahtela et al. (2010) compared gene expression from the skin fibroblasts of the 2 affected fetuses and age-matched control fetuses and observed 132 differentially expressed transcripts, 91 of which represented known genes. CHUK expression was approximately 12% of ... Lahtela et al. (2010) compared gene expression from the skin fibroblasts of the 2 affected fetuses and age-matched control fetuses and observed 132 differentially expressed transcripts, 91 of which represented known genes. CHUK expression was approximately 12% of that observed in control fibroblasts; Lahtela et al. (2010) therefore considered CHUK to be an excellent candidate gene. Lahtela et al. (2010) found that the 2 affected fetuses were homozygous for a nonsense mutation in the CHUK gene (600664.0001). Lahtela et al. (2010) found expression of MMP14 (600754) protein in affected fetuses but not in age-matched control fetuses. Kalay et al. (2012) noted similarities between fetal encasement syndrome and the Bartsocas-Papas phenotype (263650) caused by mutation in the RIPK4 gene (605706). They suggested that CHUK and RIPK4 might function via closely related pathways to promote keratinocyte differentiation and epithelial growth.