Beckwith-Wiedemann Syndrome in a Patient with Klinefelter Syndrome

摘要

Beckwith-Widemann syndrome (BWS) is a well recognized clinical syndrome with a complex multi-genetic pathogenesis due to alterations in growth regulatory genes on chromosome 11p15. BWS has a frequency of 1 in 15000 live births. It is classically characterized by a triad of exomphalos, macroglossia and gigantism.Klinefelter syndrome is the most common cause of male hypogonadism with an estimated incidence of 1 in 500-1000 live born males. Chromosome studies most often show a 47 XXY karyotype.We report a newborn with a prenatal diagnosis of Klinefelter syndrome, and diagnosed to also have BWS after birth. This is a rare and interesting association with few previous reports in literature. Introduction Beckwith-Wiedemann syndrome (BWS) is a well recognized clinical syndrome with a complex multi-genetic pathogenesis due to alterations in growth regulatory genes on chromosome 11p15. BWS has a frequency of 1 in 15000 live births. It is classically characterized by a triad of exomphalos, macroglossia and gigantism.Klinefelter syndrome is the most common cause of male hypogonadism with an estimated incidence of 1 in 500-1000 live born males [1]. Chromosome studies most often show a 47 XXY karyotype.We report a newborn with a prenatal diagnosis of Klinefelter syndrome, and diagnosed to also have BWS after birth. This is a rare and interesting association with few previous reports in literature. Case History Our patient was a male infant born to unrelated Hispanic parents. The mother was 38 years old, gravida 4 and para 1. There were 2 first trimester voluntary terminations of pregnancies. Mother had a 13 year old healthy daughter from another relationship and father had 3 other children from a previous relationship. Family history was negative for any birth defects, miscarriages, or early deaths.Prenatal ultrasound at 17 weeks gestation showed a fetal omphalocele. FISH (Fluorescent in situ hybridization) study on amniocytes revealed a 47, XXY karyotype (Fig 1), consistent with a diagnosis of Klinefelter syndrome. Maternal serum and amniotic fluid alpha-fetoprotein levels were normal at that time. The parents were counseled and followed by the division of Genetics. The mother chose to continue the pregnancy and follow-up fetal ultrasound at 28 weeks gestation showed polyhydramnios with normal fetal growth.The patient was born via repeat Cesarean section at 34 weeks gestation. Apgar scores were 6 and 7 at one and five minutes, respectively. The baby had poor cry, decreased muscle tone and respiratory distress at birth. Birth weight was 2775 grams (90th percentile), length 48cm (90th percentile) and head circumference was 33 cm (90th percentile). Physical exam was remarkable for hypoplastic flat nasal bone, hypertelorism with short palpebral features, low set ears, right ear crease, wide mouth, large tongue, widely spaced nipples, hypotonic limbs with hypoplastic fingernails, small omphalocele with umbilical cord cyst and visible small bowel, undescended testes bilaterally with right testes palpable in inguinal canal. The ear creases, macroglossia and omphalocele were all suggestive of a diagnosis of BWS and chromosomal analysis studies for the same were sent.During hospital stay of this patient, the omphalocele was reduced manually and the sac ligated at the skin level hoping for skin to close naturally. Patient did not require surgical correction of the defect. The infant required respiratory support with nasal continuous positive airway pressure (CPAP) for the first week of life. He received intravenous antibiotics for one week. He received phototherapy for physiological jaundice in the first week of life. His plasma glucose remained normal during his hospitalization. He was diagnosed with a moderate sized patent ductus arteriosus that was medically treated with intravenous Ibuprofen. There was no evidence of cardiomegaly on echocardiogram. Abdominal ultrasound did not reveal any visceromegaly and renal ultrasound was within normal limi