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Beckwith-Wiedemann syndrome(BWS)

MedGen UID:
2562
Concept ID:
C0004903
Disease or Syndrome
Synonyms: BWS; EMG Syndrome; Exomphalos macroglossia gigantism syndrome
SNOMED CT: Beckwith's syndrome (81780002); Beckwith-Wiedemann syndrome (81780002); Wiedemann-Beckwith syndrome (81780002); Exomphalos-macroglossia-gigantism syndrome (81780002)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Unknown inheritance
MedGen UID:
989040
Concept ID:
CN307042
Finding
Source: Orphanet
Hereditary clinical entity whose mode of inheritance is unknown.
 
Genes (locations): CDKN1C (11p15.4); H19-ICR (11p15.5); IGF2 (11p15.5); KCNQ1 (11p15.5-15.4); KCNQ1OT1 (11p15.5)
 
Monarch Initiative: MONDO:0007534
OMIM®: 130650
Orphanet: ORPHA116

Definition

Beckwith-Wiedemann syndrome (BWS) is a growth disorder variably characterized by neonatal hypoglycemia, macrosomia, macroglossia, hemihyperplasia, omphalocele, embryonal tumors (e.g., Wilms tumor, hepatoblastoma, neuroblastoma, and rhabdomyosarcoma), visceromegaly, adrenocortical cytomegaly, renal abnormalities (e.g., medullary dysplasia, nephrocalcinosis, medullary sponge kidney, and nephromegaly), and ear creases/pits. BWS is considered a clinical spectrum, in which affected individuals may have many of these features or may have only one or two clinical features. Early death may occur from complications of prematurity, hypoglycemia, cardiomyopathy, macroglossia, or tumors. However, the previously reported mortality of 20% is likely an overestimate given better recognition of the disorder along with enhanced treatment options. Macroglossia and macrosomia are generally present at birth but may have postnatal onset. Growth rate slows around age seven to eight years. Hemihyperplasia may affect segmental regions of the body or selected organs and tissues. [from GeneReviews]

Additional descriptions

From OMIM
Beckwith-Wiedemann syndrome is a pediatric overgrowth disorder involving a predisposition to tumor development. The clinical presentation is highly variable; some cases lack the hallmark features of exomphalos, macroglossia, and gigantism as originally described by Beckwith (1969) and Wiedemann (1969) (summary by Weksberg et al., 2010). Mussa et al. (2016) provided a review of Beckwith-Wiedemann syndrome, including the wide spectrum of phenotypic manifestations, delineation of the frequencies of manifestations according to genotype, and discussion of the molecular and epigenetic defects that underlie the disorder.  http://www.omim.org/entry/130650
From MedlinePlus Genetics
Beckwith-Wiedemann syndrome is a condition that affects many parts of the body. It is classified as an overgrowth syndrome, which means that affected infants are larger than normal (macrosomia), and some may be taller than their peers during childhood. Growth begins to slow by about age 8, and adults with this condition are not unusually tall. In some children with Beckwith-Wiedemann syndrome, specific body parts may grow abnormally large on one side of the body, leading to an asymmetric or uneven appearance. This unusual growth pattern, which is known as hemihyperplasia, usually becomes less apparent over time.

The signs and symptoms of Beckwith-Wiedemann syndrome vary among affected individuals. Some children with this condition are born with an opening in the wall of the abdomen (an omphalocele) that allows the abdominal organs to protrude through the belly-button. Other abdominal wall defects, such as a soft out-pouching around the belly-button (an umbilical hernia), are also common. Some infants with Beckwith-Wiedemann syndrome have an abnormally large tongue (macroglossia), which may interfere with breathing, swallowing, and speaking. Other major features of this condition include abnormally large abdominal organs (visceromegaly), creases or pits in the skin near the ears, low blood glucose (hypoglycemia) in infancy, and kidney abnormalities.

Children with Beckwith-Wiedemann syndrome are at an increased risk of developing several types of cancerous and noncancerous tumors, particularly a form of kidney cancer called Wilms tumor and a form of liver cancer called hepatoblastoma. Tumors develop in about 10 percent of people with this condition and almost always appear in childhood.

Most children and adults with Beckwith-Wiedemann syndrome do not have serious medical problems associated with the condition. Their life expectancy is usually normal.  https://medlineplus.gov/genetics/condition/beckwith-wiedemann-syndrome

Clinical features

From HPO
Nephroblastoma
MedGen UID:
10221
Concept ID:
C0027708
Neoplastic Process
The presence of a nephroblastoma, which is a neoplasm of the kidney that primarily affects children.
Hepatoblastoma
MedGen UID:
61644
Concept ID:
C0206624
Neoplastic Process
A kind of neoplasm of the liver that originates from immature liver precursor cells and macroscopically is composed of tissue resembling fetal or mature liver cells or bile ducts.
Gonadoblastoma
MedGen UID:
104912
Concept ID:
C0206661
Neoplastic Process
The presence of a gonadoblastoma, a neoplasm of a gonad that consists of aggregates of germ cells and sex cord elements.
Adrenal cortex carcinoma
MedGen UID:
104917
Concept ID:
C0206686
Neoplastic Process
A malignant neoplasm of the adrenal cortex that may produce hormones such as cortisol, aldosterone, estrogen, or testosterone.
Cryptorchidism
MedGen UID:
8192
Concept ID:
C0010417
Congenital Abnormality
Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).
Nephrocalcinosis
MedGen UID:
10222
Concept ID:
C0027709
Disease or Syndrome
Nephrocalcinosis is the deposition of calcium salts in renal parenchyma.
Vesicoureteral reflux
MedGen UID:
21852
Concept ID:
C0042580
Disease or Syndrome
Vesicoureteral reflux (VUR) is characterized by the reflux of urine from the bladder into the ureters and sometimes into the kidneys. It is a risk factor for urinary tract infections. Primary VUR results from a developmental defect of the ureterovesical junction (UVJ). In combination with intrarenal reflux, the resulting inflammatory reaction may result in renal injury or scarring, also called reflux nephropathy (RN). Extensive renal scarring impairs renal function and may predispose patients to hypertension, proteinuria, and renal insufficiency (summary by Lu et al., 2007). Genetic Heterogeneity of Vesicoureteral Reflux A locus designated VUR1 maps to chromosome 1p13. VUR2 (610878) is caused by mutation in the ROBO2 gene (602431) on chromosome 3p12; VUR3 (613674) is caused by mutation in the SOX17 gene (610928) on chromosome 8q11; VUR4 (614317) maps to chromosome 5; VUR5 (614318) maps to chromosome 13; VUR6 (614319) maps to chromosome 18; VUR7 (615390) maps to chromosome 12; and VUR8 (615963) is caused by mutation in the TNXB gene (600985) on chromosome 6p21. A possible X-linked form has been reported (VURX; 314550).
Nephrolithiasis
MedGen UID:
98227
Concept ID:
C0392525
Disease or Syndrome
The presence of calculi (stones) in the kidneys.
Enlarged kidney
MedGen UID:
108156
Concept ID:
C0542518
Finding
An abnormal increase in the size of the kidney.
Overgrowth of external genitalia
MedGen UID:
377097
Concept ID:
C1851722
Finding
Renal cortical cysts
MedGen UID:
370605
Concept ID:
C1969144
Finding
Cysts of the cortex of the kidney.
Cardiomegaly
MedGen UID:
5459
Concept ID:
C0018800
Finding
Increased size of the heart, clinically defined as an increased transverse diameter of the cardiac silhouette that is greater than or equal to 50% of the transverse diameter of the chest (increased cardiothoracic ratio) on a posterior-anterior projection of a chest radiograph or a computed tomography.
Cardiomyopathy
MedGen UID:
209232
Concept ID:
C0878544
Disease or Syndrome
A myocardial disorder in which the heart muscle is structurally and functionally abnormal, in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease sufficient to cause the observed myocardial abnormality.
Hemihypertrophy
MedGen UID:
90701
Concept ID:
C0332890
Congenital Abnormality
Overgrowth of only one side of the body.
Overgrowth
MedGen UID:
376550
Concept ID:
C1849265
Finding
Excessive postnatal growth which may comprise increased weight, increased length, and/or increased head circumference.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Pancreatic hyperplasia
MedGen UID:
338770
Concept ID:
C1851733
Finding
Hyperplasia of the pancreas.
Posterior helix pit
MedGen UID:
867181
Concept ID:
C4021539
Finding
Permanent indentation on the posteromedial aspect of the helix that may be sharply or indistinctly delineated.
Diastasis recti
MedGen UID:
113171
Concept ID:
C0221766
Disease or Syndrome
A separation of the rectus abdominis muscle into right and left halves (which are normally joined at the midline at the linea alba).
Large fontanelles
MedGen UID:
105329
Concept ID:
C0456132
Finding
In newborns, the two frontal bones, two parietal bones, and one occipital bone are joined by fibrous sutures, which form a small posterior fontanelle, and a larger, diamond-shaped anterior fontanelle. These regions allow for the skull to pass the birth canal and for later growth. The fontanelles gradually ossify, whereby the posterior fontanelle usually closes by eight weeks and the anterior fontanelle by the 9th to 16th month of age. Large fontanelles are diagnosed if the fontanelles are larger than age-dependent norms.
Accelerated skeletal maturation
MedGen UID:
154262
Concept ID:
C0545053
Finding
An abnormally increased rate of skeletal maturation. Accelerated skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.
Congenital omphalocele
MedGen UID:
162756
Concept ID:
C0795690
Congenital Abnormality
An omphalocele is an abdominal wall defect limited to an open umbilical ring, and is characterized by the herniation of membrane-covered internal organs into the open base of the umbilical cord. Omphalocele is distinguished from gastroschisis (230750), in which the abdominal wall defect is located laterally to a normally closed umbilical ring with herniation of organs that are uncovered by membranes (summary by Bugge, 2010). On the basis of clinical manifestations, epidemiologic characteristics, and the presence of additional malformations, Yang et al. (1992) concluded that omphalocele and gastroschisis are casually and pathogenetically distinct abdominal wall defects. Omphalocele can be a feature of genetic disorders, such as Beckwith-Wiedemann syndrome (130650) and the Shprintzen-Goldberg syndrome (182210).
Prominent occiput
MedGen UID:
381255
Concept ID:
C1853737
Finding
Increased convexity of the occiput (posterior part of the skull).
Prominent metopic ridge
MedGen UID:
387953
Concept ID:
C1857949
Finding
Vertical bony ridge positioned in the midline of the forehead.
Dandy-Walker malformation
MedGen UID:
419183
Concept ID:
C2931867
Congenital Abnormality
A congenital brain malformation typically characterized by incomplete formation of the cerebellar vermis, dilation of the fourth ventricle, and enlargement of the posterior fossa. In layman's terms, Dandy Walker malformation is a cyst in the cerebellum (typically symmetrical) that is involved with the fourth ventricle. This may interfere with the ability to drain cerebrospinal fluid from the brain, resulting in hydrocephalus. Dandy Walker cysts are formed during early embryonic development, while the brain forms. The cyst in the cerebellum typically has several blood vessels running through it connecting to the brain, thereby prohibiting surgical removal.
Neonatal hypoglycemia
MedGen UID:
57646
Concept ID:
C0158986
Finding
Blood glucose concentration below the lower limit of established reference ranges in a newborn.
Macroglossia
MedGen UID:
44236
Concept ID:
C0024421
Disease or Syndrome
Increased length and width of the tongue.
Coarse facial features
MedGen UID:
335284
Concept ID:
C1845847
Finding
Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues.
Midface retrusion
MedGen UID:
339938
Concept ID:
C1853242
Anatomical Abnormality
Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle.
Nevus flammeus
MedGen UID:
65911
Concept ID:
C0235752
Congenital Abnormality
A congenital vascular malformation consisting of superficial and deep dilated capillaries in the skin which produce a reddish to purplish discolouration of the skin.
Placental mesenchymal dysplasia
MedGen UID:
853130
Concept ID:
C1096298
Disease or Syndrome
Placental mesenchymal dysplasia is a rare anomaly characterized by placentomegaly, dilatation of chorionic vessels and hydropic stem villi with cistern-like formation. It is often clinically mistaken for a partial hydatidiform mole but there is no trophoblastic proliferation. P57 immunohistochemical expression is discordant, showing a normal positive expression in the cytotrophoblastic cells, and loss of expression in the stromal cells.
Adrenocortical cytomegaly
MedGen UID:
342072
Concept ID:
C1851720
Finding
The presence of large polyhedral cells with eosinophilic granular cytoplasm and enlarged nuclei in the adrenal cortex.
Proptosis
MedGen UID:
41917
Concept ID:
C0015300
Disease or Syndrome
An eye that is protruding anterior to the plane of the face to a greater extent than is typical.

Professional guidelines

PubMed

Larsen AR, Brusgaard K, Christesen HT, Detlefsen S
Histol Histopathol 2024 Jul;39(7):817-844. Epub 2024 Jan 12 doi: 10.14670/HH-18-709. PMID: 38305063
Brioude F, Kalish JM, Mussa A, Foster AC, Bliek J, Ferrero GB, Boonen SE, Cole T, Baker R, Bertoletti M, Cocchi G, Coze C, De Pellegrin M, Hussain K, Ibrahim A, Kilby MD, Krajewska-Walasek M, Kratz CP, Ladusans EJ, Lapunzina P, Le Bouc Y, Maas SM, Macdonald F, Õunap K, Peruzzi L, Rossignol S, Russo S, Shipster C, Skórka A, Tatton-Brown K, Tenorio J, Tortora C, Grønskov K, Netchine I, Hennekam RC, Prawitt D, Tümer Z, Eggermann T, Mackay DJG, Riccio A, Maher ER
Nat Rev Endocrinol 2018 Apr;14(4):229-249. Epub 2018 Jan 29 doi: 10.1038/nrendo.2017.166. PMID: 29377879Free PMC Article
MacFarland SP, Mostoufi-Moab S, Zelley K, Mattei PA, States LJ, Bhatti TR, Duffy KA, Brodeur GM, Kalish JM
Pediatr Blood Cancer 2017 Aug;64(8) Epub 2017 Jan 9 doi: 10.1002/pbc.26432. PMID: 28066990Free PMC Article

Recent clinical studies

Etiology

Rohowetz LJ, Kalavar M, Al-Khersan H, Kiryakoza L, Patel NA, Yannuzzi NA, Capo H, Berrocal AM
J AAPOS 2021 Oct;25(5):303-305.e1. Epub 2021 Sep 25 doi: 10.1016/j.jaapos.2021.04.012. PMID: 34582951
McCrossan S, Martin S, Hill C
J Craniofac Surg 2021 Jul-Aug 01;32(5):1856-1859. doi: 10.1097/SCS.0000000000007276. PMID: 33235175
Brioude F, Kalish JM, Mussa A, Foster AC, Bliek J, Ferrero GB, Boonen SE, Cole T, Baker R, Bertoletti M, Cocchi G, Coze C, De Pellegrin M, Hussain K, Ibrahim A, Kilby MD, Krajewska-Walasek M, Kratz CP, Ladusans EJ, Lapunzina P, Le Bouc Y, Maas SM, Macdonald F, Õunap K, Peruzzi L, Rossignol S, Russo S, Shipster C, Skórka A, Tatton-Brown K, Tenorio J, Tortora C, Grønskov K, Netchine I, Hennekam RC, Prawitt D, Tümer Z, Eggermann T, Mackay DJG, Riccio A, Maher ER
Nat Rev Endocrinol 2018 Apr;14(4):229-249. Epub 2018 Jan 29 doi: 10.1038/nrendo.2017.166. PMID: 29377879Free PMC Article
Spector LG, Birch J
Pediatr Blood Cancer 2012 Nov;59(5):776-9. Epub 2012 Jun 12 doi: 10.1002/pbc.24215. PMID: 22692949
Engström W, Lindham S, Schofield P
Eur J Pediatr 1988 Jun;147(5):450-7. doi: 10.1007/BF00441965. PMID: 3044795

Diagnosis

Mishra D, Chakole V
Pan Afr Med J 2023;45:17. Epub 2023 May 5 doi: 10.11604/pamj.2023.45.17.38741. PMID: 37426460Free PMC Article
Adams AD, Stover S, Rac MW
Prenat Diagn 2021 Mar;41(4):486-496. Epub 2021 Feb 4 doi: 10.1002/pd.5886. PMID: 33540475
Brioude F, Kalish JM, Mussa A, Foster AC, Bliek J, Ferrero GB, Boonen SE, Cole T, Baker R, Bertoletti M, Cocchi G, Coze C, De Pellegrin M, Hussain K, Ibrahim A, Kilby MD, Krajewska-Walasek M, Kratz CP, Ladusans EJ, Lapunzina P, Le Bouc Y, Maas SM, Macdonald F, Õunap K, Peruzzi L, Rossignol S, Russo S, Shipster C, Skórka A, Tatton-Brown K, Tenorio J, Tortora C, Grønskov K, Netchine I, Hennekam RC, Prawitt D, Tümer Z, Eggermann T, Mackay DJG, Riccio A, Maher ER
Nat Rev Endocrinol 2018 Apr;14(4):229-249. Epub 2018 Jan 29 doi: 10.1038/nrendo.2017.166. PMID: 29377879Free PMC Article
Choufani S, Shuman C, Weksberg R
Am J Med Genet C Semin Med Genet 2010 Aug 15;154C(3):343-54. doi: 10.1002/ajmg.c.30267. PMID: 20803657
Weksberg R, Shuman C, Beckwith JB
Eur J Hum Genet 2010 Jan;18(1):8-14. doi: 10.1038/ejhg.2009.106. PMID: 19550435Free PMC Article

Therapy

Ainuz BY, Geisler EL, Hallac RR, Perez JK, Seaward JR, Kane AA
Cleft Palate Craniofac J 2022 Sep;59(9):1145-1154. Epub 2021 Aug 17 doi: 10.1177/10556656211036607. PMID: 34402311
Li Y, Donnelly CG, Rivera RM
Vet Clin North Am Food Anim Pract 2019 Jul;35(2):265-276. doi: 10.1016/j.cvfa.2019.02.007. PMID: 31103180Free PMC Article
Lord K, De León DD
Clin Perinatol 2018 Mar;45(1):61-74. Epub 2017 Dec 6 doi: 10.1016/j.clp.2017.10.007. PMID: 29406007
Couzin-Frankel J
Science 2017 Jan 13;355(6321):122-125. doi: 10.1126/science.355.6321.122. PMID: 28082544
Spector LG, Birch J
Pediatr Blood Cancer 2012 Nov;59(5):776-9. Epub 2012 Jun 12 doi: 10.1002/pbc.24215. PMID: 22692949

Prognosis

Zenker M, Mohnike K, Palm K
Front Endocrinol (Lausanne) 2023;14:1013874. Epub 2023 Mar 30 doi: 10.3389/fendo.2023.1013874. PMID: 37065762Free PMC Article
Adams AD, Stover S, Rac MW
Prenat Diagn 2021 Mar;41(4):486-496. Epub 2021 Feb 4 doi: 10.1002/pd.5886. PMID: 33540475
Urakami T
Minerva Pediatr 2020 Dec;72(6):472-483. Epub 2020 Aug 4 doi: 10.23736/S0026-4946.20.05971-X. PMID: 32748612
Brioude F, Kalish JM, Mussa A, Foster AC, Bliek J, Ferrero GB, Boonen SE, Cole T, Baker R, Bertoletti M, Cocchi G, Coze C, De Pellegrin M, Hussain K, Ibrahim A, Kilby MD, Krajewska-Walasek M, Kratz CP, Ladusans EJ, Lapunzina P, Le Bouc Y, Maas SM, Macdonald F, Õunap K, Peruzzi L, Rossignol S, Russo S, Shipster C, Skórka A, Tatton-Brown K, Tenorio J, Tortora C, Grønskov K, Netchine I, Hennekam RC, Prawitt D, Tümer Z, Eggermann T, Mackay DJG, Riccio A, Maher ER
Nat Rev Endocrinol 2018 Apr;14(4):229-249. Epub 2018 Jan 29 doi: 10.1038/nrendo.2017.166. PMID: 29377879Free PMC Article
Arnoux JB, de Lonlay P, Ribeiro MJ, Hussain K, Blankenstein O, Mohnike K, Valayannopoulos V, Robert JJ, Rahier J, Sempoux C, Bellanné C, Verkarre V, Aigrain Y, Jaubert F, Brunelle F, Nihoul-Fékété C
Early Hum Dev 2010 May;86(5):287-94. Epub 2010 Jun 13 doi: 10.1016/j.earlhumdev.2010.05.003. PMID: 20550977

Clinical prediction guides

Zenker M, Mohnike K, Palm K
Front Endocrinol (Lausanne) 2023;14:1013874. Epub 2023 Mar 30 doi: 10.3389/fendo.2023.1013874. PMID: 37065762Free PMC Article
Urakami T
Minerva Pediatr 2020 Dec;72(6):472-483. Epub 2020 Aug 4 doi: 10.23736/S0026-4946.20.05971-X. PMID: 32748612
Li Y, Donnelly CG, Rivera RM
Vet Clin North Am Food Anim Pract 2019 Jul;35(2):265-276. doi: 10.1016/j.cvfa.2019.02.007. PMID: 31103180Free PMC Article
Brioude F, Kalish JM, Mussa A, Foster AC, Bliek J, Ferrero GB, Boonen SE, Cole T, Baker R, Bertoletti M, Cocchi G, Coze C, De Pellegrin M, Hussain K, Ibrahim A, Kilby MD, Krajewska-Walasek M, Kratz CP, Ladusans EJ, Lapunzina P, Le Bouc Y, Maas SM, Macdonald F, Õunap K, Peruzzi L, Rossignol S, Russo S, Shipster C, Skórka A, Tatton-Brown K, Tenorio J, Tortora C, Grønskov K, Netchine I, Hennekam RC, Prawitt D, Tümer Z, Eggermann T, Mackay DJG, Riccio A, Maher ER
Nat Rev Endocrinol 2018 Apr;14(4):229-249. Epub 2018 Jan 29 doi: 10.1038/nrendo.2017.166. PMID: 29377879Free PMC Article
Weksberg R, Shuman C, Beckwith JB
Eur J Hum Genet 2010 Jan;18(1):8-14. doi: 10.1038/ejhg.2009.106. PMID: 19550435Free PMC Article

Recent systematic reviews

Dietrich E, Grimaux X, Martin L, Samimi M
Ann Dermatol Venereol 2022 Dec;149(4):228-237. Epub 2022 Oct 11 doi: 10.1016/j.annder.2022.03.011. PMID: 36229262
McNickle L, Visa A, Clarke S, Yardley I, Tan YW
J Pediatr Surg 2022 Apr;57(4):661-669. Epub 2021 Jul 14 doi: 10.1016/j.jpedsurg.2021.06.016. PMID: 34311970
Kostopoulou E, Dastamani A, Güemes M, Clement E, Caiulo S, Shanmugananda P, Dattani M, Gilbert C, Hurst JA, Shah P
Clin Endocrinol (Oxf) 2021 Mar;94(3):399-412. Epub 2021 Jan 31 doi: 10.1111/cen.14393. PMID: 33345357
Han Q, Li K, Dong K, Xiao X, Yao W, Liu G
J Pediatr Surg 2018 Dec;53(12):2465-2469. Epub 2018 Sep 1 doi: 10.1016/j.jpedsurg.2018.08.022. PMID: 30274708
Cortessis VK, Azadian M, Buxbaum J, Sanogo F, Song AY, Sriprasert I, Wei PC, Yu J, Chung K, Siegmund KD
J Assist Reprod Genet 2018 Jun;35(6):943-952. Epub 2018 Apr 25 doi: 10.1007/s10815-018-1173-x. PMID: 29696471Free PMC Article

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