Facial dysmorphism and digit anomalies in three siblings with severe developmental delay Jennifer M. Mueller a , Aditi I. Dagli a , Heather J. Stalker a , Nazneen Rahman b , Roberto T. Zori a and Charles A. Williams a Clinical Dysmorphology 2011, 20:92–94 a R.C. Philips Unit, Division of Genetics and Metabolism, Department of Pediatrics, University of Florida, Gainesville, USA and b Section of Cancer Genetics, Brookes Lawley Building, Institute of Cancer Research, Sutton, Surrey, UK Correspondence to Dr Charles A. Williams, MD, Division of Genetics and Metabolism, University of Florida, 1600 SW Archer Road, PO BOX 100296, Gainesville, FL 32610, USA Tel: + 1 352 294 5050; fax: + 1 352 392 3051; e-mail: willicx@peds.ufl.edu Received 17 September 2010 Accepted 30 November 2010 List of key features Microcephaly Long philtrum, protruding ears and tongue Wilms tumor Broad thumbs and fingertips Sacral sinus Seizures Mental retardation Horseshoe kidney Two-vessel cord Clinical summary The proband (sibling 1) had abnormal nuchal thickness and a two-vessel cord diagnosed by prenatal ultrasound examination. There were protuberant ears and mild nuchal webbing at birth, and atrial septal defect, ventri- cular septal defect, and bicuspid aortic valve. Intestinal malrotation and hypothyroidism were subsequently identi- fied. The only available birth growth parameter was the birth weight (BW) of 2.99 kg (10–25%). Seizures developed at the age of 2 years and were controlled with medication. A left-sided Wilms tumor (stage II nephroblastoma) was diagnosed and removed at the age of 4 years. When seen in genetics clinic at the age of 5 years, there were severe mental retardation, protruding ears, long philtrum, protrud- ing tongue, and the toes and fingers were broad distally (radiograph of hands not available; Figs 1 and 2). Growth parameters at 6 years were weight, 18.5 kg (25%); height, 105 (< 3%); and head circumference (HC), 47 (< 2%). At the age of 7 years, he was diagnosed with moderate–mixed hearing loss. Ophthalmologic examination showed no deve- lopmental anomalies nor retinopathy. Sibling 2 also had nuchal thickening and a two-vessel cord noted prenatally, and at birth she had dysmorphic features similar to her brother. There was also bilateral lacrimal duct obstruction that required surgical correction. Growth para- meters at birth were BW, 4 kg (90%); birth length, 51 cm (75%); and HC, 35 cm (50–75%). She was diagnosed with a seizure disorder at an age of 1 year, controlled with medi- cation. Multiple abdominal ultrasounds showed no Wilms tumor but identified a horseshoe kidney. She had bilateral nasal lacrimal duct obstruction with otherwise normal ophthalmologic examination. At 3.5 years, her weight was 13.61 kg (25–50%), height was 13.61 (25–50%), and HC was 44.5 cm (< 3%). Sibling 3 also had nuchal thickening on prenatal ultrasound examination but did not have overt neck webbing at birth. Facial dysmorphism showed large ears and other anomalies similar to that of her affected siblings and there was mild congenital microcephaly, and horseshoe kidney (Table 1). Growth parameters at birth were BW, 3.16 kg (90%); birth length, 48 cm (25%); and HC, 31.5 (< 10%). Family history The father is 31 years old and of Ashkenazi Jewish and Caucasian ancestry and the mother is 31 years old of Caucasian ancestry. There are four full siblings; three affected and one unaffected girl. The couple had two miscarriages. There is also a normal maternal half-sister. There was no consanguinity and the remainder of the family history was unremarkable. Results of investigations Genetic testing The proband had normal G-band chromosome analysis, Fragile X testing, and fluorescence in-situ hybridiza- tion (FISH) analysis for Rubinstein–Taybi syndrome. Methylation-specific multiplex ligation-dependent probe amplification of 11p15 showed normal copy number variation, no uniparental disomy, and normal methylation at the H19DMR and KvDMR1. WT1 sequence analysis was normal. Glypican 3 (GPC3) gene sequencing was normal. Sibling 2 had normal chromosome and subtelo- meric FISH analyses and normal chromosomal microarray (V.5.0 Kleberg Cytogenetics Laboratory at Baylor College 92 Short case report 0962-8827  c 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI: 10.1097/MCD.0b013e3283435174 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.