CLINICAL REPORT Atypical Silver–Russell Phenotype Resulting From Maternal Uniparental Disomy of Chromosome 7 Zornitza Stark, 1 Monique M. Ryan, 2,3 Damien L. Bruno, 1 Trent Burgess, 1 and Ravi Savarirayan 1,3 * 1 Genetic Health Services Victoria, and Murdoch Children’s Research Institute, Melbourne, Australia 2 Children’s Neurosciences Centre, Royal Children’s Hospital, Melbourne, Australia 3 Department of Paediatrics, University of Melbourne, Melbourne, Australia Received 27 January 2010; Accepted 6 June 2010 We report on a patient with atypical Silver–Russell phenotype comprising severe growth retardation, unusual facies, bilateral Duane anomaly and infantile hypercalcemia caused by maternal uniparental iso/heterodisomy (mUPD) of chromosome 7. The development of myoclonus in this patient lends further support to the hypothesis that abnormal imprinting of the SGCE gene is responsible for some cases of myoclonus–dystonia syndrome. This case highlights the utility of SNP microarray technology as an accessible tool for the diagnosis of mUPD7 in atypical cases. We propose that depending on the balance of iso- and hetero- disomic segments in a particular patient, mUPD7 may result in a range of phenotypes not confined to classic Silver–Russell syn- drome. Ó 2010 Wiley-Liss, Inc. Key words: Silver–Russell syndrome; maternal uniparental dis- omy; myoclonus–dystonia syndrome; SNP microarray INTRODUCTION Uniparental disomy (UPD) is the inheritance of both homologous chromosomes from one parent [Engel, 1980]. UPD can either be isodisomic, heterodisomic, or a mixture of both depending on the etiology of meiotic non-disjunction and the occurrence of recom- bination. In all three cases (complete iso/hetero or mixed disomy), the phenotype may arise due to either the loss of imprinted genes or the unmasking of a mutation associated with recessive disease. Maternal uniparental disomy for chromosome 7 (mUPD7) has been shown to be responsible for Silver–Russel syndrome (SRS) in 10% of cases [Abu-Amero et al., 2008]. We describe a patient with severe growth retardation, unusual facies, myoclonus, infantile hypercalcemia, and bilateral Duane anomaly who did not meet the diagnostic criteria for SRS but was nevertheless shown to have mUPD7 on SNP microarray. We speculate how some of her atypical features may be related to the finding of mUPD7, and propose that mUPD7 may result in a spectrum of phenotypes depending on the balance of segments of iso- and heterodisomy in a particular patient. CLINICAL REPORT The patient, a 6-year-old girl, is the second child of non-consan- guineous Caucasian parents. She was delivered at term by cesarean for breech presentation following an uncomplicated pregnancy in a 19-year-old mother. Her birth parameters were weight 2.4 kg (<1st centile), length 43.5 cm (<10th centile), and head circumference 35 cm (50–90th centile). The subject’s early course was character- ized by feeding problems requiring supplemental nasogastric feeds, and ongoing severe postnatal growth retardation. Her height and weight continued to track below the 1st centile for age, with relative preservation of head circumference, which grew along the 50th centile. At 6 years of age, her height was 94.3 cm (<<1st centile), weight 11.5 kg (<<1st centile), and head circumference 52 cm (50–75th centile). A skeletal survey at the age of 6 years was normal. The patient has a prominent forehead (Fig. 1) and clinodactyly but no body asymmetry or pigmentary skin abnormalities. From a developmental point of view, she attends a mainstream school but required speech therapy in early childhood, and orthotics for joint laxity. Magnetic resonance imaging of the brain at age 4 years was normal. Hypercalcemia with a normal parathyroid hormone (PTH) level was noted in infancy. The patient has failure of eye abduction, consistent with bilateral type 1 Duane anomaly. No internal organ abnormalities have been identified. *Correspondence to: Ravi Savarirayan, Murdoch Childrens Research Institute, Flemington Rd, Parkville, Victoria 3052, Australia. E-mail: ravi.savarirayan@ghsv.org.au Published online 3 August 2010 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/ajmg.a.33590 How to Cite this Article: Stark Z, Ryan MM, Bruno DL, Burgess T, Savarirayan R. 2010. Atypical Silver–Russell phenotype resulting from maternal uniparental disomy of chromosome 7. Am J Med Genet Part A 152A:2342–2345. Ó 2010 Wiley-Liss, Inc. 2342