A newborn boy is being examined in the newborn nursery. He was born at term to a 34-year-old primigravida via spontaneous vaginal delivery. The mother had routine prenatal care with an uneventful pregnancy, and family history is unremarkable. Weight, length, and head circumference are at the 25thpercentile. Examination shows an awake newborn with normal tone. The anterior fontanel is open and flat. The ears are in the normal position. Eye examination shows absence of the iris in both eyes. Examination of the oropharynx reveals an intact palate. Cardiopulmonary examination is normal. The abdomen is soft and the liver edge is palpable. Genitourinary examination shows the urethral opening at the ventral side of the penile shaft. The left testis is not palpable but the right testis is present. Examination of the skin and extremities is normal. This patient is at increased risk of developing which of the following disorders?

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11ec25c8_d735_b25f_bc81_25f86295e8e3_MD0003_00 This newborn's absent irises and genitourinary anomalies (ie, hypospadias, cryptorchidism) raise suspicion for WAGR syndrome/11p deletion syndrome. WAGR syndrome typically results from a de novo gene deletion on chromosome 11p13 and is an acronym for its associated conditions (Wilms tumor, Aniridia [absent iris], Genitourinary abnormalities, and intellectual disability [previously mental Retardation]). The diagnosis should be suspected if 2 or more of these conditions are present and confirmed with genetic testing. Wilms tumor (nephroblastoma) is a renal malignancy that occurs in approximately half of patients with WAGR syndrome and is due to deletion of the WT1 gene within the affected chromosome region. Wilms tumors are more often bilateral and present earlier (age 1-3) in WAGR syndrome than in isolation. Screening abdominal ultrasound is performed every 3 months in infancy and early childhood for early detection and treatment. Despite strict surveillance, end-stage renal disease develops in many patients. (Choice A) Down syndrome increases the risk for acute myeloid leukemia. Classical examination findings include a single palmar crease, upslanting palpebral fissures, and small, low-set ears, none of which is seen here. In addition, Down syndrome is associated with Brushfield spots (white spots on the iris), not aniridia. Down syndrome (Choice B) Multiple endocrine neoplasia syndrome type 2, an inherited autosomal dominant disorder, predisposes patients to medullary thyroid cancer, pheochromocytoma, and hyperparathyroidism. It is not associated with genitourinary abnormalities or aniridia and is unlikely in this patient with no family history of tumors. (Choice C) Increased risk of embryonal tumors such as Wilms tumor, hepatoblastoma, and neuroblastoma occurs with Beckwith-Wiedemann syndrome. However, other findings associated with this condition, such as hemihyperplasia, macroglossia, and macrosomia, are not seen in this patient. (Choice D) Optic pathway gliomas occur in young children with neurofibromatosis type 1, a neurocutaneous disorder characterized by café au lait macules, axillary freckling, and neurofibromas, none of which is seen here. Lisch nodules (hamartomas) can form in the iris; aniridia is not a feature. neurofibromatosis type 1 (Choice E) Retinoblastoma presents in infants and young children with leukocoria (white pupillary reflex) and is not associated with absent irises or genitourinary abnormalities. Educational objective: WAGR syndrome/11p deletion syndrome is characterized by a predisposition to Wilms tumor and the presence of Aniridia, Genitourinary abnormalities, and intellectual disability (previously mental Retardation). WAGR syndrome should be considered in a child with 2 or more of the associated conditions. In patients with WAGR syndrome, screening abdominal ultrasound is performed every 3 months in infancy and early childhood for early detection of Wilms tumor. References: Wilms tumor predisposition. (http://www.ncbi.nlm.nih.gov/pubmed/20301471) Wilms tumor: an update. (http://www.ncbi.nlm.nih.gov/pubmed/24713986)

A Newborn Boy Is Being Examined in the Newborn Nursery