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Pancreatic hypoplasia-diabetes-congenital heart disease syndrome(PACHD; HDCA)

MedGen UID:
444022
Concept ID:
C2931296
Disease or Syndrome
Synonyms: HEART DEFECTS, CONGENITAL, AND OTHER CONGENITAL ANOMALIES; Pancreatic agenesis and congenital heart disease; PANCREATIC HYPOPLASIA, CONGENITAL, WITH DIABETES MELLITUS AND CONGENITAL HEART DISEASE
SNOMED CT: Pancreatic hypoplasia, diabetes mellitus, congenital heart disease syndrome (722206009); Yorifuji Okuno syndrome (722206009)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
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 individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
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.
 
Gene (location): GATA6 (18q11.2)
 
Monarch Initiative: MONDO:0010802
OMIM®: 600001
Orphanet: ORPHA2255

Definition

This syndrome has characteristics of partial pancreatic agenesis, diabetes mellitus, and heart anomalies (including transposition of the great vessels, ventricular or atrial septal defects, pulmonary stenosis, or patent ductus arteriosis). It has been described in one Japanese family, in which the mother and at least two of her four children were affected (another two children died shortly after birth). The syndrome appears to be inherited as an autosomal dominant trait. [from SNOMEDCT_US]

Clinical features

From HPO
Glycosuria
MedGen UID:
42267
Concept ID:
C0017979
Finding
An increased concentration of glucose in the urine.
Ureteral duplication
MedGen UID:
66380
Concept ID:
C0221365
Congenital Abnormality
A developmental anomaly characterized by the presence of two, instead of one, ureter connecting a kidney to the bladder.
Patent ductus arteriosus
MedGen UID:
4415
Concept ID:
C0013274
Congenital Abnormality
In utero, the ductus arteriosus (DA) serves to divert ventricular output away from the lungs and toward the placenta by connecting the main pulmonary artery to the descending aorta. A patent ductus arteriosus (PDA) in the first 3 days of life is a physiologic shunt in healthy term and preterm newborn infants, and normally is substantially closed within about 24 hours after bith and completely closed after about three weeks. Failure of physiologcal closure is referred to a persistent or patent ductus arteriosus (PDA). Depending on the degree of left-to-right shunting, PDA can have clinical consequences.
Patent foramen ovale
MedGen UID:
8891
Concept ID:
C0016522
Congenital Abnormality
Failure of the foramen ovale to seal postnatally, leaving a potential conduit between the left and right cardiac atria.
Atrial septal defect
MedGen UID:
6753
Concept ID:
C0018817
Congenital Abnormality
Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum.
Ventricular septal defect
MedGen UID:
42366
Concept ID:
C0018818
Congenital Abnormality
A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum.
Tetralogy of Fallot
MedGen UID:
21498
Concept ID:
C0039685
Congenital Abnormality
People with CCHD have one or more specific heart defects. The heart defects classified as CCHD include coarctation of the aorta, double-outlet right ventricle, D-transposition of the great arteries, Ebstein anomaly, hypoplastic left heart syndrome, interrupted aortic arch, pulmonary atresia with intact septum, single ventricle, total anomalous pulmonary venous connection, tetralogy of Fallot, tricuspid atresia, and truncus arteriosus.\n\nEach of the heart defects associated with CCHD affects the flow of blood into, out of, or through the heart. Some of the heart defects involve structures within the heart itself, such as the two lower chambers of the heart (the ventricles) or the valves that control blood flow through the heart. Others affect the structure of the large blood vessels leading into and out of the heart (including the aorta and pulmonary artery). Still others involve a combination of these structural abnormalities.\n\nSome people with treated CCHD have few related health problems later in life. However, long-term effects of CCHD can include delayed development and reduced stamina during exercise. Adults with these heart defects have an increased risk of abnormal heart rhythms, heart failure, sudden cardiac arrest, stroke, and premature death.\n\nAlthough babies with CCHD may appear healthy for the first few hours or days of life, signs and symptoms soon become apparent. These can include an abnormal heart sound during a heartbeat (heart murmur), rapid breathing (tachypnea), low blood pressure (hypotension), low levels of oxygen in the blood (hypoxemia), and a blue or purple tint to the skin caused by a shortage of oxygen (cyanosis). If untreated, CCHD can lead to shock, coma, and death. However, most people with CCHD now survive past infancy due to improvements in early detection, diagnosis, and treatment.\n\nCritical congenital heart disease (CCHD) is a term that refers to a group of serious heart defects that are present from birth. These abnormalities result from problems with the formation of one or more parts of the heart during the early stages of embryonic development. CCHD prevents the heart from pumping blood effectively or reduces the amount of oxygen in the blood. As a result, organs and tissues throughout the body do not receive enough oxygen, which can lead to organ damage and life-threatening complications. Individuals with CCHD usually require surgery soon after birth.
Transposition of the great arteries
MedGen UID:
21245
Concept ID:
C0040761
Congenital Abnormality
Critical congenital heart disease (CCHD) is a term that refers to a group of serious heart defects that are present from birth. These abnormalities result from problems with the formation of one or more parts of the heart during the early stages of embryonic development. CCHD prevents the heart from pumping blood effectively or reduces the amount of oxygen in the blood. As a result, organs and tissues throughout the body do not receive enough oxygen, which can lead to organ damage and life-threatening complications. Individuals with CCHD usually require surgery soon after birth.\n\nAlthough babies with CCHD may appear healthy for the first few hours or days of life, signs and symptoms soon become apparent. These can include an abnormal heart sound during a heartbeat (heart murmur), rapid breathing (tachypnea), low blood pressure (hypotension), low levels of oxygen in the blood (hypoxemia), and a blue or purple tint to the skin caused by a shortage of oxygen (cyanosis). If untreated, CCHD can lead to shock, coma, and death. However, most people with CCHD now survive past infancy due to improvements in early detection, diagnosis, and treatment.\n\nSome people with treated CCHD have few related health problems later in life. However, long-term effects of CCHD can include delayed development and reduced stamina during exercise. Adults with these heart defects have an increased risk of abnormal heart rhythms, heart failure, sudden cardiac arrest, stroke, and premature death.\n\nEach of the heart defects associated with CCHD affects the flow of blood into, out of, or through the heart. Some of the heart defects involve structures within the heart itself, such as the two lower chambers of the heart (the ventricles) or the valves that control blood flow through the heart. Others affect the structure of the large blood vessels leading into and out of the heart (including the aorta and pulmonary artery). Still others involve a combination of these structural abnormalities.\n\nPeople with CCHD have one or more specific heart defects. The heart defects classified as CCHD include coarctation of the aorta, double-outlet right ventricle, D-transposition of the great arteries, Ebstein anomaly, hypoplastic left heart syndrome, interrupted aortic arch, pulmonary atresia with intact septum, single ventricle, total anomalous pulmonary venous connection, tetralogy of Fallot, tricuspid atresia, and truncus arteriosus.
Persistent truncus arteriosus
MedGen UID:
52867
Concept ID:
C0041207
Congenital Abnormality
A single arterial trunk arises from the cardiac mass. The pulmonary arteries, aorta and coronary arteries arise from this single trunk with no evidence of another outflow tract.
Aortic arch interruption
MedGen UID:
57773
Concept ID:
C0152419
Congenital Abnormality
Non-continuity of the arch of aorta with an atretic point or absent segment.
Pulmonary artery stenosis
MedGen UID:
65965
Concept ID:
C0238397
Anatomical Abnormality
An abnormal narrowing or constriction of the pulmonary artery, in the main pulmonary artery and/or in the left or right pulmonary artery branches.
Double outlet left ventricle
MedGen UID:
120558
Concept ID:
C0265809
Congenital Abnormality
A congenital defect of heart development characterized by origin of both pulmonary artery and aorta from the morphological left ventricle.
Hypoplastic tricuspid valve
MedGen UID:
472995
Concept ID:
C0265837
Congenital Abnormality
Congenital defect characterized by underdevelopment of the tricuspid valve.
Perimembranous ventricular septal defect
MedGen UID:
87490
Concept ID:
C0344925
Congenital Abnormality
A ventricular septal defect that is confluent with and involves the membranous septum and is bordered by an atrioventricular valve, not including the type 3 VSDs.
Total absence of the pericardium
MedGen UID:
576786
Concept ID:
C0345140
Congenital Abnormality
No pericardium around the heart, occurring as a congenital defect, not the result of a surgical pericardectomy.
Pulmonic stenosis
MedGen UID:
408291
Concept ID:
C1956257
Disease or Syndrome
A narrowing of the right ventricular outflow tract that can occur at the pulmonary valve (valvular stenosis), below the pulmonary valve (infundibular stenosis), or above the pulmonary valve (supravalvar stenosis).
Fetal growth restriction
MedGen UID:
4693
Concept ID:
C0015934
Pathologic Function
An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Biliary atresia
MedGen UID:
14117
Concept ID:
C0005411
Congenital Abnormality
Atresia of the biliary tree.
Intestinal malrotation
MedGen UID:
113153
Concept ID:
C0221210
Congenital Abnormality
An abnormality of the intestinal rotation and fixation that normally occurs during the development of the gut. This can lead to volvulus, or twisting of the intestine that causes obstruction and necrosis.
Microcolon
MedGen UID:
82734
Concept ID:
C0266200
Congenital Abnormality
A colon of abnormally small caliber.
Isolated agenesis of gallbladder
MedGen UID:
82736
Concept ID:
C0266251
Congenital Abnormality
A developmental defect in which the gallbladder fails to form.
Pancreatic hypoplasia
MedGen UID:
539808
Concept ID:
C0266267
Congenital Abnormality
Hypoplasia of the pancreas.
Colon perforation
MedGen UID:
87582
Concept ID:
C0347646
Disease or Syndrome
A hole (perforation) in the wall of the colon.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Inguinal hernia
MedGen UID:
6817
Concept ID:
C0019294
Finding
Protrusion of the contents of the abdominal cavity through the inguinal canal.
Umbilical hernia
MedGen UID:
9232
Concept ID:
C0019322
Anatomical Abnormality
Protrusion of abdominal contents through a defect in the abdominal wall musculature around the umbilicus. Skin and subcutaneous tissue overlie the defect.
Cervical rib
MedGen UID:
102359
Concept ID:
C0158779
Congenital Abnormality
Presence of rib formation in the cervical region.
Congenital diaphragmatic hernia
MedGen UID:
68625
Concept ID:
C0235833
Congenital Abnormality
The presence of a hernia of the diaphragm present at birth.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Aplasia of the left hemidiaphragm
MedGen UID:
1680550
Concept ID:
C5194758
Finding
Congenital absence of the left half of the diaphragm.
Diabetes mellitus
MedGen UID:
8350
Concept ID:
C0011849
Disease or Syndrome
A group of abnormalities characterized by hyperglycemia and glucose intolerance.
Hyperglycemia
MedGen UID:
5689
Concept ID:
C0020456
Disease or Syndrome
An increased concentration of glucose in the blood.
Single umbilical artery
MedGen UID:
278026
Concept ID:
C1384670
Congenital Abnormality
Single umbilical artery (SUA) is the absence of one of the two umbilical arteries surrounding the fetal bladder and in the fetal umbilical cord.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVPancreatic hypoplasia-diabetes-congenital heart disease syndrome
Follow this link to review classifications for Pancreatic hypoplasia-diabetes-congenital heart disease syndrome in Orphanet.

Professional guidelines

PubMed

Cuthbertson DJ, Shankland R, Srirajaskanthan R
Clin Med (Lond) 2023 Mar;23(2):119-124. doi: 10.7861/clinmed.2023-0044. PMID: 36958842Free PMC Article
Platts-Mills TAE, Li RC, Keshavarz B, Smith AR, Wilson JM
J Allergy Clin Immunol Pract 2020 Jan;8(1):15-23.e1. Epub 2019 Sep 28 doi: 10.1016/j.jaip.2019.09.017. PMID: 31568928Free PMC Article
Lane ER, Hsu EK, Murray KF
Expert Rev Gastroenterol Hepatol 2015;9(10):1281-92. Epub 2015 Sep 1 doi: 10.1586/17474124.2015.1083419. PMID: 26325252

Recent clinical studies

Etiology

Efremova I, Maslennikov R, Poluektova E, Vasilieva E, Zharikov Y, Suslov A, Letyagina Y, Kozlov E, Levshina A, Ivashkin V
World J Gastroenterol 2023 Jun 14;29(22):3400-3421. doi: 10.3748/wjg.v29.i22.3400. PMID: 37389240Free PMC Article
Chen J, Yuan S, Fu T, Ruan X, Qiao J, Wang X, Li X, Gill D, Burgess S, Giovannucci EL, Larsson SC
Diabetes Care 2023 Apr 1;46(4):828-835. doi: 10.2337/dc22-1385. PMID: 36800530Free PMC Article
Yuan S, Chen J, Ruan X, Sun Y, Zhang K, Wang X, Li X, Gill D, Burgess S, Giovannucci E, Larsson SC
Elife 2023 Feb 2;12 doi: 10.7554/eLife.84051. PMID: 36727839Free PMC Article
Larsson SC, Burgess S
EBioMedicine 2022 Aug;82:104154. Epub 2022 Jul 8 doi: 10.1016/j.ebiom.2022.104154. PMID: 35816897Free PMC Article
Douillard C, Jannin A, Vantyghem MC
Ann Endocrinol (Paris) 2020 Jun;81(2-3):110-117. Epub 2020 Apr 10 doi: 10.1016/j.ando.2020.04.003. PMID: 32409005

Diagnosis

Yoshimi A, Ishikawa K, Niemeyer C, Grünert SC
Orphanet J Rare Dis 2022 Oct 17;17(1):379. doi: 10.1186/s13023-022-02538-9. PMID: 36253820Free PMC Article
Paul J, Shihaz AVH
Arq Gastroenterol 2020 Apr-Jun;57(2):216-220. doi: 10.1590/s0004-2803.202000000-27. PMID: 32490903
Douillard C, Jannin A, Vantyghem MC
Ann Endocrinol (Paris) 2020 Jun;81(2-3):110-117. Epub 2020 Apr 10 doi: 10.1016/j.ando.2020.04.003. PMID: 32409005
Platts-Mills TAE, Li RC, Keshavarz B, Smith AR, Wilson JM
J Allergy Clin Immunol Pract 2020 Jan;8(1):15-23.e1. Epub 2019 Sep 28 doi: 10.1016/j.jaip.2019.09.017. PMID: 31568928Free PMC Article
Vienberg S, Geiger J, Madsen S, Dalgaard LT
Acta Physiol (Oxf) 2017 Feb;219(2):346-361. Epub 2016 Apr 5 doi: 10.1111/apha.12681. PMID: 27009502Free PMC Article

Therapy

Chen J, Yuan S, Fu T, Ruan X, Qiao J, Wang X, Li X, Gill D, Burgess S, Giovannucci EL, Larsson SC
Diabetes Care 2023 Apr 1;46(4):828-835. doi: 10.2337/dc22-1385. PMID: 36800530Free PMC Article
Yuan S, Chen J, Ruan X, Sun Y, Zhang K, Wang X, Li X, Gill D, Burgess S, Giovannucci E, Larsson SC
Elife 2023 Feb 2;12 doi: 10.7554/eLife.84051. PMID: 36727839Free PMC Article
Larsson SC, Burgess S
EBioMedicine 2022 Aug;82:104154. Epub 2022 Jul 8 doi: 10.1016/j.ebiom.2022.104154. PMID: 35816897Free PMC Article
Laurindo LF, Barbalho SM, Guiguer EL, da Silva Soares de Souza M, de Souza GA, Fidalgo TM, Araújo AC, de Souza Gonzaga HF, de Bortoli Teixeira D, de Oliveira Silva Ullmann T, Sloan KP, Sloan LA
Int J Mol Sci 2022 Jan 10;23(2) doi: 10.3390/ijms23020739. PMID: 35054924Free PMC Article
Lane ER, Hsu EK, Murray KF
Expert Rev Gastroenterol Hepatol 2015;9(10):1281-92. Epub 2015 Sep 1 doi: 10.1586/17474124.2015.1083419. PMID: 26325252

Prognosis

Efremova I, Maslennikov R, Poluektova E, Vasilieva E, Zharikov Y, Suslov A, Letyagina Y, Kozlov E, Levshina A, Ivashkin V
World J Gastroenterol 2023 Jun 14;29(22):3400-3421. doi: 10.3748/wjg.v29.i22.3400. PMID: 37389240Free PMC Article
Chen J, Yuan S, Fu T, Ruan X, Qiao J, Wang X, Li X, Gill D, Burgess S, Giovannucci EL, Larsson SC
Diabetes Care 2023 Apr 1;46(4):828-835. doi: 10.2337/dc22-1385. PMID: 36800530Free PMC Article
Yuan S, Chen J, Ruan X, Sun Y, Zhang K, Wang X, Li X, Gill D, Burgess S, Giovannucci E, Larsson SC
Elife 2023 Feb 2;12 doi: 10.7554/eLife.84051. PMID: 36727839Free PMC Article
Platts-Mills TAE, Li RC, Keshavarz B, Smith AR, Wilson JM
J Allergy Clin Immunol Pract 2020 Jan;8(1):15-23.e1. Epub 2019 Sep 28 doi: 10.1016/j.jaip.2019.09.017. PMID: 31568928Free PMC Article
Holman RR, Bethel MA, Mentz RJ, Thompson VP, Lokhnygina Y, Buse JB, Chan JC, Choi J, Gustavson SM, Iqbal N, Maggioni AP, Marso SP, Öhman P, Pagidipati NJ, Poulter N, Ramachandran A, Zinman B, Hernandez AF; EXSCEL Study Group
N Engl J Med 2017 Sep 28;377(13):1228-1239. Epub 2017 Sep 14 doi: 10.1056/NEJMoa1612917. PMID: 28910237Free PMC Article

Clinical prediction guides

Chen J, Ruan X, Fu T, Lu S, Gill D, He Z, Burgess S, Giovannucci EL, Larsson SC, Deng M, Yuan S, Li X
EBioMedicine 2024 May;103:105110. Epub 2024 Apr 6 doi: 10.1016/j.ebiom.2024.105110. PMID: 38583262Free PMC Article
Chen J, Yuan S, Fu T, Ruan X, Qiao J, Wang X, Li X, Gill D, Burgess S, Giovannucci EL, Larsson SC
Diabetes Care 2023 Apr 1;46(4):828-835. doi: 10.2337/dc22-1385. PMID: 36800530Free PMC Article
Yuan S, Chen J, Ruan X, Sun Y, Zhang K, Wang X, Li X, Gill D, Burgess S, Giovannucci E, Larsson SC
Elife 2023 Feb 2;12 doi: 10.7554/eLife.84051. PMID: 36727839Free PMC Article
Laurindo LF, Barbalho SM, Guiguer EL, da Silva Soares de Souza M, de Souza GA, Fidalgo TM, Araújo AC, de Souza Gonzaga HF, de Bortoli Teixeira D, de Oliveira Silva Ullmann T, Sloan KP, Sloan LA
Int J Mol Sci 2022 Jan 10;23(2) doi: 10.3390/ijms23020739. PMID: 35054924Free PMC Article
Platts-Mills TAE, Li RC, Keshavarz B, Smith AR, Wilson JM
J Allergy Clin Immunol Pract 2020 Jan;8(1):15-23.e1. Epub 2019 Sep 28 doi: 10.1016/j.jaip.2019.09.017. PMID: 31568928Free PMC Article

Recent systematic reviews

Horváth IL, Bunduc S, Hankó B, Kleiner D, Demcsák A, Szabó B, Hegyi P, Csupor D
Sci Rep 2023 Feb 16;13(1):2791. doi: 10.1038/s41598-023-29939-5. PMID: 36797320Free PMC Article
Larsson SC, Burgess S
EBioMedicine 2022 Aug;82:104154. Epub 2022 Jul 8 doi: 10.1016/j.ebiom.2022.104154. PMID: 35816897Free PMC Article
Aziz H, Lashkari N, Yoon YC, Kim J, Sher LS, Genyk Y, Kwon YK
Transplant Proc 2020 Nov;52(9):2642-2653. Epub 2020 Sep 15 doi: 10.1016/j.transproceed.2020.09.006. PMID: 33127076Free PMC Article
Nikolic S, Dugic A, Steiner C, Tsolakis AV, Haugen Löfman IM, Löhr JM, Vujasinovic M
World J Gastroenterol 2019 Nov 28;25(44):6561-6570. doi: 10.3748/wjg.v25.i44.6561. PMID: 31802835Free PMC Article
Joish VN, Shah S, Tierce JC, Patel D, McKee C, Lapuerta P, Zacks J
Future Oncol 2019 Apr;15(12):1397-1406. Epub 2019 Feb 8 doi: 10.2217/fon-2018-0960. PMID: 30734573

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