Beckwith-Wiedemann Syndrome

1. Beckwith-Wiedemann syndrome (BWS): The association of macrosomia (88%, enlarged body size: birth weight > 90%, ↑postnatal growth), macroglossia (97%, enlarged tongue大舌), and omphalocele(80%, 臍膨出).
2. Other associated findings include mild facial dysmorphism (hypertelorism, unusual ear creases), infantile hypoglycemia due to transient hyperinsulinemia (63%, due to pancreatic hyperplasia), multiple congenital anomalies (cleft palate and genitourinary anomalies common), hemihyperplasia (asymmetrical overgrowth of a limb or one side of the face or trunk), and umbilical hernia, gigantism(巨人症), fetal adrenocortical cytomegaly, and large kidneys with medullary dysplasia.…
3. 和PMH有很大的關係：Placental mesenchymal hyperplasia (PMH)
1. a rare placental anomaly characterized by: (1) placentomegaly, (2) dilated chorionic plate vessels, and (3) grape-like vesicles, which are dilated villi.
2. PMH may be associated with an uneventful pregnancy and normal fetus. However, it may also be associated with clinically important fetal sequelae that include fetal growth restriction, intrauterine death, preterm delivery, fetal anomalies, fetal anemia, and a high association with BWS.
3. BWS的母親可能會有：Viseromegaly, placentomegaly
4. Related to abnormal expression of genes located at chromosome 11p15.5, sporadic major, possibly familial.
1. 在11p上有一些基因imprint於其上，可能是從父親(paternally)或母親(maternally)傳下來的。目前找到了兩個地方，叫做differentially methylated regions (DMRs)，可稱為DMR1, DMR2。
2. 染色體的異常會影響基因的表現：A growth factor gene, IGF2, is imprinted in DMR1。而母方的allele基本上在intrauterine development時是不表現的(inactive)，但父方則否(paternally active)，所以正常人只有一份active。若異常使得父方(paternal) 11p15 region做了兩份(約20~30%的病人是這種情形，叫作uniparental disomy)，或是母方的imprint丟失，這會使active IGF2 gene效果加倍!! IGF2在fetal development時製造增加，所以BWS的小孩會overgrowth。
3. 而50~60%的病人是因為失去了父親的(paternal) imprint of DMR2(包含如KCNQ1, CDKN1C之類的基因)，這會silence掉growth inhibitors，這樣解釋小孩也會overgrowth且得到tumor的機會會增加，然而詳細的機轉仍不明。
4. 而BWS也跟Paternal UPD有關，Paternal UPD可能會導致H19 不表現，而H19是一個tumor suppressor gene(通常來自母方 maternal homolog)！這樣也可以解釋BWS容易得到癌症的情形，約70% of Wilms tumors from patients with BWS show loss of imprinting of the genes coding for IGF2 and H19.
5. increased risk for certain malignancies, especially Wilms tumor (7–10%), hepatoblastoma, bilateral pheochromocytomas → 早期發現早期治療
6. Children affected with BWS should undergo tumor surveillance protocols, including an abdominal ultrasound every 3 months until they reach age 7 years, as diagnosing malignancy at early stages leads to a significant improvement in outcome.
7. 其他參考資料可參考財團法人罕見疾病基金會：http://www.tfrd.org.tw/rare/typeCont.php?sno=1505&kind_id=15 

Ref:

1. CURRENT Diagnosis & Treatment: Pediatrics > Chapter 35. Genetics & Dysmorphology > Nonmendelian Disorders > Disorders of Imprinting
2. Greenspan's Basic & Clinical Endocrinology > Chapter 7. Growth > Disorders of Growth > Tall Stature Due to Nonendocrine Causes > Syndromes of Tall Stature
3. Greenspan's Basic & Clinical Endocrinology > Chapter 12. Adrenal Medulla & Paraganglia > Pheochromocytoma > Genetic Conditions Associated with Pheochromocytomas & Paragangliomas > Other Genetic Syndromes Associated with Pheochromocytoma
4. Williams Hematology, 8e > Chapter 10. Genomics and Epigenetics > Genomics and Epigenetics > Genomic Imprinting
5. Williams Obstetrics, 23e Clinical Pearls: Placental Mesenchymal Hyperplasia