Prenatal diagnosis of Pena-Shokeir syndrome phenotype by ultrasonography and MR imaging
- First Online:
- 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
- 182 Views
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.
KeywordsAmyoplasia congenitaPena-Shokeir syndromeMRIPrenatal diagnosisFetus
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 . 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.
Pena and Shokeir described this condition in two siblings with camptodactyly, arthrogryposis, facial anomalies and pulmonary hypoplasia in 1974 . In 1983, Moessinger  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 . 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 . This theory is also supported by a study by Tongsong et al. , 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 . 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 .
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 . 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 . In the study by Mulder et al. , 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.  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 . 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.