Confirming the involvement of PIEZO2 in the etiology of Marden-Walker syndrome.

Pathogenic heterozygous variants in PIEZO2 typically cause distal arthrogryposis type 5 (DA5) and the closely related Gordon syndrome (GS). Only one case of PIEZO2-related Marden-Walker syndrome (MWS) has been reported to date. We report the phenotypic features of a Saudi female patient with features consistent with MWS in whom we identified a novel de novo likely pathogenic variant in PIEZO2. Our case lends support to the link between PIEZO2 and MWS.

The windblown hand - diagnosis, clinical picture and pathogenesis.

The syndrome of the windblown hand deformity is a complex constellation of malformations affecting not only the head and the feet but also the hands in a quite distinct manner. In the hand, it involves congenital bilateral flexion contracture with ulnar deviation of the metacarpophalangeal joints. The thumb is characteristically adducted (reaching the palm; "thumb-in-palm deformity") with flexion of the MP joint and hyperextension of the IP joint. The etiology is basically unknown. We present two theories based on knowledge derived from the disciplines of evolution biology and embryology. We believe that the atavistic appearance of phylogenetically primitive muscle groups in conjunction with an impaired rotation of the extremities during embryological development account for this malformation syndrome.

Prenatal diagnosis of arthrogryposis multiplex congenita with increased nuchal translucency but without any underlying fetal neurogenic or myogenic pathology.

Arthrogryposis multiplex congenita is a general term for congenital multiple joint contractures, the aetiology of which is variable. Prenatal diagnosis is usually based on the detection of diminished fetal movements and joint contractures on ultrasound. There are also reports of early diagnosis of arthrogryposis in the first and early second trimester by detection of subcutaneous oedema. We report another case of arthrogryposis multiplex congenita with increased nuchal translucency and scoliosis diagnosed by ultrasonography at 15 weeks of gestation. The pregnancy was terminated at the request of the parents. Post-mortem examination revealed that it was not associated with fetal myopathy or neuropathy. Multiple joint contractures with increased nuchal translucency without any underlying fetal neurogenic and myogenic pathology may be a distinct form of arthrogryposis multiplex congenita.

Geleophysic dysplasia: a report of three affected boys--prenatal ultrasound does not detect recurrence.

Geleophysic dysplasia is characterized by short stature with short limbs and brachydactyly, a "happy" facial appearance, and joint contractures. Infiltration of heart valves and liver with a mucopolysaccharide-like substance has been demonstrated in some patients. A metabolic pathogenesis is suspected, but has not yet been identified. We report on 3 boys with the condition, 2 of whom are brothers. Serial ultrasound scans were performed on 2 of the cases during pregnancy, but short limbs did not become obvious until after 28 weeks of gestation, making it an uninformative procedure for prenatal diagnosis.

Pulmonary hypoplasia and deformations related to premature rupture of membranes.

In summary, fetal pulmonary development occurs in three phases. Hypoplasia results when an interruption occurs in or before the canalicular stage. Factors necessary for normal lung growth include sustained adequate amniotic fluid volume and normal fetal breathing movements. Pulmonary hypoplasia is most likely to occur with a very early rupture of membranes (less than 22 weeks) and with persistent oligohydramnios. Lack of sustained breathing movements and failure of modulation of ductal flow are strongly associated. Ultrasound measurement of fetal lung length may eventually be useful in monitoring intrauterine pulmonary development. Limb contractures resulting from prolonged oligohydramnios are examples of deformation-type defects. Their presence correlates most strongly with the length of the latent period (time from ROM to delivery) and the degree of oligohydramnios. Most contractures of this type are readily reversible. Early amnion rupture sequence, presumed to result from rupture of only the amnion in the first trimester, is associated with multiple severe fetal deformations. It usually occurs sporadically, with a minimal recurrence risk.

The fetal akinesia deformation sequence. A fetopathological approach.

In this paper we review the present knowledge on the etiological factors and pathogenetic mechanisms of the fetal akinesia deformation sequence, based on a fetopathological approach. Special attention is given to two sever, lethal subgroups i.e. the Pena-Shokeir I syndrome and the lethal multiple pterygium syndrome.

Fetal akinesia deformation sequence in previable fetuses.

We reviewed the morphologic findings of 948 previable fetuses and identified the fetal akinesia deformation sequence (FADS) in 16 cases. In eight fetuses who had joint contractures, micrognathia, and pulmonary hypoplasia, the cause of fetal akinesia could be attributed to an abnormal intrauterine environment restricting fetal movement. The other eight fetuses had pterygia across the immobilized joints, in addition to main manifestations of FADS. Since most of the fetuses with pterygia were of only 8-9 weeks developmental age, we suggest that embryonic onset of immobility interferes with limb development and results in joint fixation and pterygium formation, in contrast to fetal-onset immobility, which causes joint contractures alone.

Radio ultrasound observations of the fetotoxic effects in sheep from ingestion of Conium maculatum (poison-hemlock).

Fetal movement in pregnant ewes gavaged with Conium maculatum (poison-hemlock) was reduced significantly, but temporarily. Fetal movement was observed by radio ultrasound at 45, 54 and 60 days of gestation in control ewes and on days 45, 54, and 60 of gestation immediately before and 1 hour following poison-hemlock feeding in treated ewes. Fetal movement was significantly reduced (P less than 0.01) 1 hour after poison-hemlock administration, but returned to normal within 18 hours post treatment. At parturition seven of eleven lambs born to seven treated ewes had varying degrees of front limb abnormalities. Modest to moderate flexure of the carpal joints, some lateral deviation in the front limbs at the pastern joint and kinked tails were observed. These malformations were transient and resolved spontaneously by 8 weeks after lambing.