Pediatric Radiology

, Volume 39, Issue 4, pp 377–380

Prenatal diagnosis of Pena-Shokeir syndrome phenotype by ultrasonography and MR imaging

Authors

  • Efsun Urger Senocak
    • Department of RadiologyHacettepe University Faculty of Medicine
    • Department of RadiologyHacettepe University Faculty of Medicine
  • Goknur Haliloglu
    • Department of Pediatric NeurologyHacettepe University Faculty of Medicine
  • Deniz Karcaaltincaba
    • Department of Obstetrics and GynaecologyEtlik Zubeyde Hanim Woman’s Hospital
  • Deniz Akata
    • Department of RadiologyHacettepe University Faculty of Medicine
  • Omer Kandemir
    • Department of Obstetrics and GynaecologyEtlik Zubeyde Hanim Woman’s Hospital
Case Report

DOI: 10.1007/s00247-008-1121-5

Cite this article as:
Senocak, E.U., Oguz, K.K., Haliloglu, G. et al. Pediatr Radiol (2009) 39: 377. doi:10.1007/s00247-008-1121-5

Abstract

Pena-Shokeir syndrome phenotype is characterized by neurogenic arthrogryposis, facial anomalies, polyhydramnios and lung hypoplasia. Prenatal US is crucial in showing Pena-Shokeir syndrome phenotype in addition to demonstrating reduced fetal movements or akinesia as an underlying aetiological factor as early as the 14th week of gestation. Several reports of prenatal diagnosis of Pena-Shokeir syndrome phenotype by US have been published. In this report, MRI findings providing prenatal diagnosis are presented.

Keywords

Amyoplasia congenitaPena-Shokeir syndromeMRIPrenatal diagnosisFetus

Introduction

Pena-Shokeir (PS) syndrome phenotype is an autosomal recessive disorder with an estimated frequency of 1:12,000 births. It is characterized by intrauterine growth restriction, neurogenic arthrogryposis, facial anomalies, polyhydramnios and lung hypoplasia [1]. We believe this is the first description of the fetal MR findings of this peculiar syndrome. Pre- or postnatal MR imaging can be used as an adjunct to US, especially for the evaluation of accompanying central nervous system (CNS) malformations. In this case the CNS was normal, but MRI documented remarkable atrophy of the muscles and limb contractures.

Case report

A 27-year-old primigravid woman at 32 weeks of gestation was referred to our department for level 2 obstetric US and fetal MRI. She had no history of familial disease, drug abuse, or systemic illness. US and MRI revealed a single fetus with polyhydramnios. On US the biparietal diameter (82.3 mm) and femur length (64.5 mm) were consistent with the gestational date (33 weeks), while the abdominal circumference (262 mm) revealed growth restriction (30 weeks). The fetus made no active movements and the fetal posture did not change throughout the US or the MRI scans. The lower limbs were extended and he had a right clubfoot. The fingers were flexed and the elbows extended (Fig. 1). There was diffuse atrophy of the muscles with thickening of the subcutaneous tissue that appeared T2-hyperintense on MRI and hyperechoic on US (Fig. 2). Gastric fluid was not visible on either examination. The lungs were hypoplastic; cardiac size was relatively large because of the small thoracic cage. He had micrognathia with a prominent beak-like protrusion of the nose (Fig. 2). The remainder of the evaluation, including the brain and spine, was unremarkable. These findings were consistent with the PS syndrome phenotype. The parents were informed of the diagnosis and its prognosis, but they decided to continue with the pregnancy. Delivery occurred at 37 weeks of gestation and the infant died soon after his birth.
https://static-content.springer.com/image/art%3A10.1007%2Fs00247-008-1121-5/MediaObjects/247_2008_1121_Fig1_HTML.gif
Fig. 1

Limbs. Grey-scale US images (a, c) and axial HASTE MR images (b, d) of the extremities show that the fingers of the upper limbs are flexed with the elbows extended (a, bwhite arrows). The legs and feet are extended (cwhite arrow) and there is a right clubfoot (dblack arrow)

https://static-content.springer.com/image/art%3A10.1007%2Fs00247-008-1121-5/MediaObjects/247_2008_1121_Fig2_HTML.gif
Fig. 2

MR images. a, b Sagittal (a) and coronal (b) HASTE images demonstrate polyhydramnios, hypoplastic lungs, small thoracic cage and increased cardiothoracic ratio (bwhite arrows). There is no fluid in the stomach. There is micrognathia with a prominent beak-like protrusion of the nose (a). c On the image of the lower limbs there is marked atrophy of the muscles of the extremities (white lines) with fatty replacement (black arrow) and thick subcutaneous tissue (black lines). d Normal fetus for comparison

Discussion

Pena and Shokeir described this condition in two siblings with camptodactyly, arthrogryposis, facial anomalies and pulmonary hypoplasia in 1974 [1]. In 1983, Moessinger [2] performed an experimental study in which rat fetuses were paralysed by daily transuterine injection of curare from day 18 until term. At the time of delivery multiple joint contractures, pulmonary hypoplasia, micrognathia, fetal growth retardation, short umbilical cord, and polyhydramnios were noted, bearing a striking similarity to the PS syndrome phenotype. He postulated that this phenotype is not specific, but rather represents a fetal akinesia deformation sequence that results from fetal immobilization or akinesia. The basis for this theory is that use and motion are necessary for normal fetal development.

Muscle atrophy, and abnormal shape and position of the limbs are due to lack of normal motion [3]. Diaphragmatic and intercostal muscle dysfunction results in loss of rhythmic thoracic movements resembling respiration, and leads to a small thoracic cage and lung hypoplasia. Development of the lung is arrested in the canalicular phase at about 15 weeks of gestation, which is also a critical period for joint development. Depressed swallowing is probably responsible for polyhydramnios and an empty stomach. Lack of muscle pull at sites of normal attachment may lead to craniofacial anomalies [3]. This theory is also supported by a study by Tongsong et al. [1], which demonstrated regional akinesia involving only the upper limbs and some parts of the face and chest with polyhydramnios in a woman at 28 weeks of gestation. The upper limbs and chest had no movement and became hypoplastic, whereas the lower part of the body showed completely normal activity and morphology.

The major differential diagnoses include Freeman Sheldon syndrome, multiple pterygium syndrome, trisomy 18, trisomy 13, Potter syndrome, Neu-Laxova syndrome, restrictive dermopathy, Larsen syndrome, and cerebro-ocular-facial-skeletal syndrome [3, 4]. Among these, pulmonary hypoplasia is only found with Potter syndrome; however, the presence of severe oligohydramnios in this condition differentiates it from PS syndrome [3]. PS syndrome phenotype has a poor prognosis. Some of these babies are born prematurely and those born at term are small for gestational age. The majority die of complications due to pulmonary hypoplasia in the first week of life [4].

We used MRI especially to assess the CNS for the abnormalities that have been reported with PS phenotype. The CNS was normal in our patient; however, the appearance of muscle atrophy with accompanying fatty replacement was striking. The total size of bone and muscle was reduced and we observed extensive T2 hyperintensity of the bone–muscle complex compared with the skin. Although we did not have T1-weighted or STIR images, with the assistance of US we attributed this appearance to atrophy and fatty replacement secondary to chronic denervation. On US we observed abnormal and extensive echogenicity of the subcutaneous tissue due to replacement with fat. The observation of fatty change in chronically denervated muscles suggests an irreversible process [5]. Other characteristic features including lung hypoplasia, increased cardiothoracic ratio with small thoracic cage and contractures were also well visualized.

Despite the similar phenotype described in patients with PS syndrome, comparisons of pathological findings are difficult because of the limited number of reports describing the complete histopathological picture. Autopsy findings include hypoplasia of the cerebellum, thin cerebral and cerebellar cortices and neuronal migration disorders [6]. In the study by Mulder et al. [7], microscopic examination of the brain (cerebrum, cerebellum and cranial nerve motor nuclei) and spinal motor neurons showed no abnormalities in PS phenotype. Tongsong et al. [1] found some degree of diffuse and group atrophy of skeletal muscles, consistent with neurogenic atrophy, and reduction of the anterior horn motor cells in the cervical and thoracic spinal cord. In another infant, histological examination of the muscles revealed many small muscle fibres in a mixed rather than a group distribution, although the structure was normally arranged. Detailed examination revealed failure of differentiation into type I fibres and retardation of skeletal muscle [8]. These abnormalities suggest that a mesenchymal disorder in the pathogenesis of PS syndrome is more likely than immaturity of the CNS. Although autopsy findings were not available in our case because of lack of parental consent, atrophy of skeletal muscles was shown by MRI.

Prenatal diagnosis with US is feasible as early as the 14th week of gestation. It plays an important role by demonstrating the characteristic and diagnostic features of PS syndrome phenotype and is a valuable screening tool for prenatal diagnosis and genetic counselling. By demonstrating these characteristic intrauterine MR imaging findings radiologists can diagnose PS syndrome phenotype prenatally. In cases with arthrogryposis, fetal MR imaging should be used to document abnormalities throughout the body in addition to the CNS, and hence facilitate appropriate management.

Copyright information

© Springer-Verlag 2009