- Email: [email protected]
Total anomalous pulmonary venous drainage in association with Kaufman syndrome
Journal Pre-proof Total anomalous pulmonary venous drainage in association with Kaufman syndrome
Abdelmonem Helal, M.H. Mashali, Iman Sabri Abumansour, Mohammad Omar Galal, Amjad Kouatli PII:
S1058-9813(19)30125-0
DOI:
https://doi.org/10.1016/j.ppedcard.2019.101165
Reference:
PPC 101165
To appear in:
Progress in Pediatric Cardiology
Received date:
25 August 2019
Revised date:
14 September 2019
Accepted date:
17 September 2019
Please cite this article as: A. Helal, M.H. Mashali, I.S. Abumansour, et al., Total anomalous pulmonary venous drainage in association with Kaufman syndrome, Progress in Pediatric Cardiology(2018), https://doi.org/10.1016/j.ppedcard.2019.101165
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
© 2018 Published by Elsevier.
Journal Pre-proof
Total anomalous pulmonary venous drainage in association with Kaufman syndrome Abdelmonem Helal1, 2, Mashali MH1.2, Iman Sabri Abumansour3, 4, Mohammad Omar Galal1, Amjad Kouatli1 1
Department of Pediatric, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia 2
of
Department of Pediatric Cardiology, Kasr Alainy Faculty of Medicine, Cairo University, Cairo, Egypt Pediatric Department, King Faisal Specialist Hospital and Research Center, Jeddah
4
Medical Genetic Department, Medical College, Umm Al-Qura University, Makkah
re
Correspondence: [email protected] Abdelmonem Helal
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ABSTRACT:
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Kaufman oculo-cerebro-facial syndrome is a rare autosomal recessive disease with very few cases have been reported in the literature. We present a case of Kaufman oculo-cerebro-facial syndrome with mutation in gene Ubiquitin Protein Ligase E3B (UBE3B) associated with total anomalous pulmonary venous drainage. This association as far as we know has not been previously reported.
Jo
Keywords: Kaufman oculo-cerebro-facial syndrome, total anomalous pulmonary venous drainage, UBE3B. CASE REPORT:
A newborn male patient, who is the first child of consanguineous marriage, presented after birth with vomiting, poor feeding, respiratory distress and cyanosis. He has facial dysmorphic features including frontal bossing, highly arched eyebrows, up slanted palpebral fissures, flat phlitrum, cleft palate and micrognathia. He has large rounded low set ears, with underdeveloped antihelix. He was noted to have bilateral squint and nystagmus. Ophthalmological examination showed deep-seated eyes, infantile exotropia with cross fixing, mild myopic astigmatism and right inferior oblique over action. The child has left palmar transverse, clenched hand, and clinodactyly of 5th fingers bilaterally (Figure 1). Cardiac exam showed a hyperdynamic precordium, a widely split second heart sound with a loud pulmonary component, and a grade 3/6 systolic ejection murmur audible along the left sternal border. Echocardiography revealed
Journal Pre-proof
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ro
of
atrial septal defect (ASD II) with right to left shunt and total anomalous pulmonary venous drainage (TAPVD)- as pulmonary veins were making confluence that draining close to superior vena cava to right atrium junction with turbulence of flow showed mean pressure gradient of 8 mmHg. Surgical repair for TAPVD with closure of ASD was performed on urgent bases at age of two months .The right atrium was opened and enlarged ASD; this allowed us to unroof the left atrial root to do anastomosis of the venous confluence to the left atrial roof and then ASD was closed with a large baffle allowing the pulmonary veins to drain into the left atrium.The patient was followed for 2.5 years with no stenosis of the pulmonary venous drainage and no other residual cardiac lesions. Neurologically, he has global developmental delay and hypotonia. Karyotype showed normal 46, XY result. Microarray did not reveal any pathogenic Copy Number variant (CNV). Sanger sequencing targeting known common mutation (c.155166del12bp) in Tubulin-specific chaperone E (TBCE)gene was requested and result was negative. Whole exome sequencing revealed a homozygous pathogenic variant in UBE3B (NM_130466: exon15: c.1622+1G>A) confirming the diagnosis of Kaufman oculo-cerebrofacial syndrome.We start counceling the family for doing family screening tests.
lP
re
A written consent was taken from the parents including the permission to take photographs of their child and use these photographs in our publication
DISCUSSION
na
Kaufman oculo-cerebro-facial syndrome (KOS) is a rare autosomal recessive disorder. As of last reported cases May 2019, around 19 individuals have been reported with this disease. (6, 10)
Jo
ur
It is mainly characterized by severe psychomotor retardation, microcephaly, hypotonia, ocular abnormalities, low cholesterol levels and distinctive facial dysmorphisms. (1) Facial features include hypertelorism, epicanthus, upslanted palpebral fissures, and short palpebral fissures, lowset, posteriorly angulated and round ears with narrow external meati (2). Variable features include seizures, hypoplasia/aplasia of corpus callosum, and renal anomalies. Less common findings include: unilateral or bilateral conductive hearing loss, congenital heart defects; breathing problems; feeding difficulties; urogenital abnormalities; and/or skeletal abnormalities.(3) The diagnosis of Kaufman oculocerebrofacial syndrome is usually established in a proband once biallelic UBE3B pathogenic variants are detected. (4) Cardiac defects reported with Kaufman syndrome include pulmonary artery stenosis, atrial septal defect, ventricular septal defect and aortic coarctation (4) As far as we know, TAPVD has not been reported before.
Figure 1:
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Journal Pre-proof
A- Cleft palate B- Low set ear, squint and frontal bossing C- Palmar transverse crease D- Clenched hand
Journal Pre-proof
of
Whole exome sequencing has emerged as comperehensive and cost effective approach to identify pathogenic variants of rare genetic syndromes. It has helped in revealing the full spectrum of genetic diseases linked to particular genes especially in cases with uncommon features suggesting phenotype expansion of a disorder. In 2015 Pedurupillay CR et al reported two novel compound heterozygous mutations in UBE3B in 2 sisters (suggest unique features seen in these cases) by exome sequencing. In 2017 Kariminejad A et al reported Kaufman oculo-cerebro-facial syndrome in a child with small and absent terminal phalanges and absent nails.
Jo
ur
na
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re
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ro
Based on our literature review, TAPVD was not reported before in Kaufman oculo-cerebrofacial syndrome. Also, no association between UBE3B mutation and isolated TAPVD was observed previously. (9) Therefore, we report this case of TAPVD as part of Kaufman oculocerebro-facial syndrome to expand the types of cardiac defects associated with this syndrome.Due to criticl clinical condition on presentation ,Patient underwent surgical repair before final diagnosis from genetic point of view .During the follow up period , patient never admitted in hospital ,feeding well and following his normal growth percentiles.That intervention had good positive impact on the patient and his family .We recommend 1) searching for genetic disorder in any patient with dysmorphic features especially with complex cardiac lesions. 2)Mangment of clinical condition at least with palliative intervention till having final genetic results and counseling.
Journal Pre-proof
REFERENCE: 1: Kaufman RL, Rimoin DL, Prensky AL, Sly WS. An oculocerebrofacial syndrome. Birth Defects Orig Artic Ser. 1971 Feb; 7(1):135-8. PubMed PMID: 5006210.
of
2: Pedurupillay CR, Barøy T, Holmgren A, Blomhoff A, Vigeland MD, Sheng Y, Frengen E, Strømme P, Misceo D. Kaufman oculocerebrofacial syndrome in sisterswith novel compound heterozygous mutation in UBE3B. Am J Med Genet A. 2015 Mar; 167A (3):657-63. doi: 10.1002/ajmg.a.36944. PubMed PMID: 25691420.
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3: Kariminejad A, Ajeawung NF, Bozorgmehr B, Dionne-Laporte A, Molidperee S, Najafi K, Gibbs RA, Lee BH, Hennekam RC, Campeau PM. Kaufman oculo-cerebro-facial syndrome in a child with small and absent terminal phalanges and absent nails. J Hum Genet. 2017 Apr; 62(4):465-471. doi:10.1038/jhg.2016.151. Epub 2016 Dec 22.PubMed PMID: 28003643; PubMed Central PMCID: PMC5370204.
na
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4: Basel-Vanagaite L, Dallapiccola B, Ramirez-Solis R, Segref A, Thiele H, Edwards A, Arends MJ, Miró X, White JK, Désir J, Abramowicz M, Dentici ML, Lepri F, Hofmann K, Har-Zahav A, Ryder E, Karp NA, Estabel J, Gerdin AK, Podrini C, Ingham NJ, Altmüller J, Nürnberg G, Frommolt P, Abdelhak S, Pasmanik-Chor M, Konen O, Kelley RI, Shohat M, Nürnberg P, Flint J, Steel KP, Hoppe T, Kubisch C, Adams DJ, Borck G. Deficiency for the ubiquitin ligase UBE3B in a blepharophimosis-ptosis-intellectual-disability syndrome. Am J Hum Genet. 2012 Dec 7; 91(6):998-1010. doi: 10.1016/j.ajhg.2012.10.011
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5: Basel-Vanagaite L, Yilmaz R, Tang S, Reuter MS, Rahner N, Grange DK, Mortenson M, Koty P, Feenstra H, Farwell Gonzalez KD, Sticht H, Boddaert N, Désir J, Anyane-Yeboa K, Zweier C, Reis A, Kubisch C, Jewett T, Zeng W, Borck G. Expanding the clinical and mutational spectrum of Kaufman oculocerebrofacial syndrome with biallelic UBE3B mutations. Hum Genet. 2014; 133:939–49 6: Basel-Vanagaite L, Borck G. Kaufman Oculocerebrofacial Syndrome. 2016 Oct 20.In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, Editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019. 7: Kariminejad A, Ajeawung NF, Bozorgmehr B, Dionne-Laporte A, Molidperee S, Najafi K, Gibbs RA, Lee BH, Hennekam RC, Campeau PM. Kaufman oculo-cerebro-facial Syndrome in a child with small and absent terminal phalanges and absent nails. J Hum Genet. 2017 Apr; 62(4):465-471. doi: 10.1038/jhg.2016.151. Epub 2016 Dec 22 8: Seale A, Carvalho J, Gardiner H, Mellander M, Roughton M, Simpson J. Total anomalous pulmonary venous connection: impact of prenatal diagnosis. Ultrasound Obstet Gynecol. 2012 Jan 20.
Journal Pre-proof 9: Nash D, Arrington CB, Kennedy BJ, Yandell M, Wu W, Zhang W, Shared Segment Analysis and Next-Generation Sequencing Implicates the Retinoic Acid Signaling Pathway in Total Anomalous Pulmonary Venous Return (TAPVR). PLoS ONE 10(6): e0131514. PLoS One. 2015 Jun 29; 10(6): e0131514. doi: 10.1371/journal.pone.0131514. Collection 2015.
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10: Galarreta CI, Wigby KM, Jones MC. Further phenotypic characterization of Kaufman oculocerebrofacial syndrome: report of five new cases and literature review. Clin Dysmorphol. 2019 May 30. doi: 10.1097/MCD.0000000000000282.
Journal Pre-proof
Highlights Kaufman syndrome is a very rare disease only few cases published till now The disease known to be associated with congenital cardiac disorder. Never described with total anomalous pulmonary venous return.
Jo
ur
na
lP
re
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Patient underwent successful surgical repair.
Figure 1
Abdelmonem Helal, M.H. Mashali, Iman Sabri Abumansour, Mohammad Omar Galal, Amjad Kouatli PII:
S1058-9813(19)30125-0
DOI:
https://doi.org/10.1016/j.ppedcard.2019.101165
Reference:
PPC 101165
To appear in:
Progress in Pediatric Cardiology
Received date:
25 August 2019
Revised date:
14 September 2019
Accepted date:
17 September 2019
Please cite this article as: A. Helal, M.H. Mashali, I.S. Abumansour, et al., Total anomalous pulmonary venous drainage in association with Kaufman syndrome, Progress in Pediatric Cardiology(2018), https://doi.org/10.1016/j.ppedcard.2019.101165
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
© 2018 Published by Elsevier.
Journal Pre-proof
Total anomalous pulmonary venous drainage in association with Kaufman syndrome Abdelmonem Helal1, 2, Mashali MH1.2, Iman Sabri Abumansour3, 4, Mohammad Omar Galal1, Amjad Kouatli1 1
Department of Pediatric, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia 2
of
Department of Pediatric Cardiology, Kasr Alainy Faculty of Medicine, Cairo University, Cairo, Egypt Pediatric Department, King Faisal Specialist Hospital and Research Center, Jeddah
4
Medical Genetic Department, Medical College, Umm Al-Qura University, Makkah
re
Correspondence: [email protected] Abdelmonem Helal
-p
ro
3
lP
ABSTRACT:
ur
na
Kaufman oculo-cerebro-facial syndrome is a rare autosomal recessive disease with very few cases have been reported in the literature. We present a case of Kaufman oculo-cerebro-facial syndrome with mutation in gene Ubiquitin Protein Ligase E3B (UBE3B) associated with total anomalous pulmonary venous drainage. This association as far as we know has not been previously reported.
Jo
Keywords: Kaufman oculo-cerebro-facial syndrome, total anomalous pulmonary venous drainage, UBE3B. CASE REPORT:
A newborn male patient, who is the first child of consanguineous marriage, presented after birth with vomiting, poor feeding, respiratory distress and cyanosis. He has facial dysmorphic features including frontal bossing, highly arched eyebrows, up slanted palpebral fissures, flat phlitrum, cleft palate and micrognathia. He has large rounded low set ears, with underdeveloped antihelix. He was noted to have bilateral squint and nystagmus. Ophthalmological examination showed deep-seated eyes, infantile exotropia with cross fixing, mild myopic astigmatism and right inferior oblique over action. The child has left palmar transverse, clenched hand, and clinodactyly of 5th fingers bilaterally (Figure 1). Cardiac exam showed a hyperdynamic precordium, a widely split second heart sound with a loud pulmonary component, and a grade 3/6 systolic ejection murmur audible along the left sternal border. Echocardiography revealed
Journal Pre-proof
-p
ro
of
atrial septal defect (ASD II) with right to left shunt and total anomalous pulmonary venous drainage (TAPVD)- as pulmonary veins were making confluence that draining close to superior vena cava to right atrium junction with turbulence of flow showed mean pressure gradient of 8 mmHg. Surgical repair for TAPVD with closure of ASD was performed on urgent bases at age of two months .The right atrium was opened and enlarged ASD; this allowed us to unroof the left atrial root to do anastomosis of the venous confluence to the left atrial roof and then ASD was closed with a large baffle allowing the pulmonary veins to drain into the left atrium.The patient was followed for 2.5 years with no stenosis of the pulmonary venous drainage and no other residual cardiac lesions. Neurologically, he has global developmental delay and hypotonia. Karyotype showed normal 46, XY result. Microarray did not reveal any pathogenic Copy Number variant (CNV). Sanger sequencing targeting known common mutation (c.155166del12bp) in Tubulin-specific chaperone E (TBCE)gene was requested and result was negative. Whole exome sequencing revealed a homozygous pathogenic variant in UBE3B (NM_130466: exon15: c.1622+1G>A) confirming the diagnosis of Kaufman oculo-cerebrofacial syndrome.We start counceling the family for doing family screening tests.
lP
re
A written consent was taken from the parents including the permission to take photographs of their child and use these photographs in our publication
DISCUSSION
na
Kaufman oculo-cerebro-facial syndrome (KOS) is a rare autosomal recessive disorder. As of last reported cases May 2019, around 19 individuals have been reported with this disease. (6, 10)
Jo
ur
It is mainly characterized by severe psychomotor retardation, microcephaly, hypotonia, ocular abnormalities, low cholesterol levels and distinctive facial dysmorphisms. (1) Facial features include hypertelorism, epicanthus, upslanted palpebral fissures, and short palpebral fissures, lowset, posteriorly angulated and round ears with narrow external meati (2). Variable features include seizures, hypoplasia/aplasia of corpus callosum, and renal anomalies. Less common findings include: unilateral or bilateral conductive hearing loss, congenital heart defects; breathing problems; feeding difficulties; urogenital abnormalities; and/or skeletal abnormalities.(3) The diagnosis of Kaufman oculocerebrofacial syndrome is usually established in a proband once biallelic UBE3B pathogenic variants are detected. (4) Cardiac defects reported with Kaufman syndrome include pulmonary artery stenosis, atrial septal defect, ventricular septal defect and aortic coarctation (4) As far as we know, TAPVD has not been reported before.
Figure 1:
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Journal Pre-proof
A- Cleft palate B- Low set ear, squint and frontal bossing C- Palmar transverse crease D- Clenched hand
Journal Pre-proof
of
Whole exome sequencing has emerged as comperehensive and cost effective approach to identify pathogenic variants of rare genetic syndromes. It has helped in revealing the full spectrum of genetic diseases linked to particular genes especially in cases with uncommon features suggesting phenotype expansion of a disorder. In 2015 Pedurupillay CR et al reported two novel compound heterozygous mutations in UBE3B in 2 sisters (suggest unique features seen in these cases) by exome sequencing. In 2017 Kariminejad A et al reported Kaufman oculo-cerebro-facial syndrome in a child with small and absent terminal phalanges and absent nails.
Jo
ur
na
lP
re
-p
ro
Based on our literature review, TAPVD was not reported before in Kaufman oculo-cerebrofacial syndrome. Also, no association between UBE3B mutation and isolated TAPVD was observed previously. (9) Therefore, we report this case of TAPVD as part of Kaufman oculocerebro-facial syndrome to expand the types of cardiac defects associated with this syndrome.Due to criticl clinical condition on presentation ,Patient underwent surgical repair before final diagnosis from genetic point of view .During the follow up period , patient never admitted in hospital ,feeding well and following his normal growth percentiles.That intervention had good positive impact on the patient and his family .We recommend 1) searching for genetic disorder in any patient with dysmorphic features especially with complex cardiac lesions. 2)Mangment of clinical condition at least with palliative intervention till having final genetic results and counseling.
Journal Pre-proof
REFERENCE: 1: Kaufman RL, Rimoin DL, Prensky AL, Sly WS. An oculocerebrofacial syndrome. Birth Defects Orig Artic Ser. 1971 Feb; 7(1):135-8. PubMed PMID: 5006210.
of
2: Pedurupillay CR, Barøy T, Holmgren A, Blomhoff A, Vigeland MD, Sheng Y, Frengen E, Strømme P, Misceo D. Kaufman oculocerebrofacial syndrome in sisterswith novel compound heterozygous mutation in UBE3B. Am J Med Genet A. 2015 Mar; 167A (3):657-63. doi: 10.1002/ajmg.a.36944. PubMed PMID: 25691420.
-p
ro
3: Kariminejad A, Ajeawung NF, Bozorgmehr B, Dionne-Laporte A, Molidperee S, Najafi K, Gibbs RA, Lee BH, Hennekam RC, Campeau PM. Kaufman oculo-cerebro-facial syndrome in a child with small and absent terminal phalanges and absent nails. J Hum Genet. 2017 Apr; 62(4):465-471. doi:10.1038/jhg.2016.151. Epub 2016 Dec 22.PubMed PMID: 28003643; PubMed Central PMCID: PMC5370204.
na
lP
re
4: Basel-Vanagaite L, Dallapiccola B, Ramirez-Solis R, Segref A, Thiele H, Edwards A, Arends MJ, Miró X, White JK, Désir J, Abramowicz M, Dentici ML, Lepri F, Hofmann K, Har-Zahav A, Ryder E, Karp NA, Estabel J, Gerdin AK, Podrini C, Ingham NJ, Altmüller J, Nürnberg G, Frommolt P, Abdelhak S, Pasmanik-Chor M, Konen O, Kelley RI, Shohat M, Nürnberg P, Flint J, Steel KP, Hoppe T, Kubisch C, Adams DJ, Borck G. Deficiency for the ubiquitin ligase UBE3B in a blepharophimosis-ptosis-intellectual-disability syndrome. Am J Hum Genet. 2012 Dec 7; 91(6):998-1010. doi: 10.1016/j.ajhg.2012.10.011
Jo
ur
5: Basel-Vanagaite L, Yilmaz R, Tang S, Reuter MS, Rahner N, Grange DK, Mortenson M, Koty P, Feenstra H, Farwell Gonzalez KD, Sticht H, Boddaert N, Désir J, Anyane-Yeboa K, Zweier C, Reis A, Kubisch C, Jewett T, Zeng W, Borck G. Expanding the clinical and mutational spectrum of Kaufman oculocerebrofacial syndrome with biallelic UBE3B mutations. Hum Genet. 2014; 133:939–49 6: Basel-Vanagaite L, Borck G. Kaufman Oculocerebrofacial Syndrome. 2016 Oct 20.In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, Editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019. 7: Kariminejad A, Ajeawung NF, Bozorgmehr B, Dionne-Laporte A, Molidperee S, Najafi K, Gibbs RA, Lee BH, Hennekam RC, Campeau PM. Kaufman oculo-cerebro-facial Syndrome in a child with small and absent terminal phalanges and absent nails. J Hum Genet. 2017 Apr; 62(4):465-471. doi: 10.1038/jhg.2016.151. Epub 2016 Dec 22 8: Seale A, Carvalho J, Gardiner H, Mellander M, Roughton M, Simpson J. Total anomalous pulmonary venous connection: impact of prenatal diagnosis. Ultrasound Obstet Gynecol. 2012 Jan 20.
Journal Pre-proof 9: Nash D, Arrington CB, Kennedy BJ, Yandell M, Wu W, Zhang W, Shared Segment Analysis and Next-Generation Sequencing Implicates the Retinoic Acid Signaling Pathway in Total Anomalous Pulmonary Venous Return (TAPVR). PLoS ONE 10(6): e0131514. PLoS One. 2015 Jun 29; 10(6): e0131514. doi: 10.1371/journal.pone.0131514. Collection 2015.
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ur
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re
-p
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10: Galarreta CI, Wigby KM, Jones MC. Further phenotypic characterization of Kaufman oculocerebrofacial syndrome: report of five new cases and literature review. Clin Dysmorphol. 2019 May 30. doi: 10.1097/MCD.0000000000000282.
Journal Pre-proof
Highlights Kaufman syndrome is a very rare disease only few cases published till now The disease known to be associated with congenital cardiac disorder. Never described with total anomalous pulmonary venous return.
Jo
ur
na
lP
re
-p
ro
of
Patient underwent successful surgical repair.
Figure 1