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Intestinal Pseudo-Obstruction - Patent Ductus Arteriosus - Natal Teeth

Natal Teeth, Intestinal Pseudoobstruction and Patent Ductus

Intestinal pseudo-obstruction (IPO), patent ductus arteriosus (PDA), and natal teeth (NT) have been described as a lethal syndrome in the newborn. Two male siblings have been reported by Harris et al. in 1976, and it may be speculated whether these cases represent a broadening of the clinical phenotype of X-linked chronic idiopathic neuronal IPO, as defined more than 20 years later.


Both patients described by Harris et al. were born at term after uneventful pregnancies; they were male and apparently healthy at birth [1]. Meconium was not passed, however, and the neonates started to vomit bile-stained material shortly after birth, so they were referred for diagnostic imaging of the gastrointestinal tract. Radiographs showed delayed gastric emptying and air-fluid levels suggestive of intestinal obstruction, midgut malrotation, and a relatively small colon. Beyond that, a left diaphragmatic hernia was discovered in one of the patients. These findings were confirmed intraoperatively, when the children were intervened for intestinal malrotation and, in the case of the firstborn, organ herniation through the diaphragmatic opening. Even though no anatomic obstruction of the digestive tract was demonstrable, gastrointestinal motility could not be stimulated after surgery in either case, and signs and symptoms of intestinal obstruction persisted until the boys' death at 6 weeks and 5 months of age, respectively. Of note, the older brother was found to have a ventral hernia when undergoing reoperation.

Additionally, auscultation revealed heart murmurs consistent with PDA in both patients. During the second week of life, the older brother presented symptoms of cardiac failure. He responded poorly to medical therapy and underwent cardiac catheterization, which confirmed the presence of a large PDA. As for the younger sibling, he had a systolic murmur best heard at the left sternal border. His PDA was confirmed by means of electrocardiography and radiography.

The older brother had two mandibular teeth and similar observations were made in the second patient.

  • Acute inflammation of these cysts because of a rupture is often mistaken as an infection. Antibiotics have very little value in these cases. Incision with drainage under local anesthesia will help with comfort as well as limit scarring.[mulpix.com]
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  • Odontogenic hamartomas are tumour-like lesions, without the growth characteristics of a neoplasm, and develop during the time dental structures remain capable of further development and maturation38.breast106, inflammation of the surrounding tissues,[vdocuments.mx]
  • The Fraenum by Consequently, there exist anatomic (not adequate zone of attached gingiva), biologic (inflammation, inability for Oral Surgery Approach good oral hygiene) and functional (inability for protection Oral surgeons accused an abnormal fraenum[datenpdf.com]
Surgical Procedure
  • Minor preprosthetic surgical procedures. Dent Clin North Am, 1994; 38(2):193-216. Correspondence and request for offprints to:Prof.[vdocuments.mx]
  • Minor preprosthetic surgical procedures. Dent Clin North Am, 1994; 38(2):193-216. Correspondence and request for offprints to: Prof.[datenpdf.com]
  • The definitive surgical procedure has been debated (2,5,8,9,15). Colonic patch graft procedures were the first proposals for surgical management of TCA (14).[pongpdf.com]
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  • […] nervous system lymphoma, primary * Central nervous system protozoal infections * Central pontine myelinolysis * Central serous chorioretinopathy * Centromeric instability immunodeficiency syndrome * Centronuclear myopathy, congenital * Centrotemporal epilepsy[medicalgeek.com]
  • This diagnostic capability could be of great utility to the physician. In this observational study, we sought to determine if observed NIRS measurements were associated with the presence or absence of an hsPDA.[nature.com]
  • The presence of an abnormally dilated gastric bubble in prenatal sonography should alert the physician toward the diagnosis of congenital antro-pyloric obstruction.[pongpdf.com]
  • Two-third of cases appear as a complication of other illness: trauma, shock, burns, sepsis, and operative procedures.[pongpdf.com]
  • Late diagnosis ( 30 wks) should be delivered in tertiary center prepare to deal with dystocia and postnatal dyspnea of newborn. The airway should be secured before cord clamping in huge lesions.[pongpdf.com]
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  • […] exacerbated in pregnancy [PATH: hsa04960 ] H01619 Primary pulmonary hypertension [PATH: hsa04350 ] H01621 Pulmonary arterial hypertension [PATH: hsa04350 ] H01622 Chronic thromboembolic pulmonary hypertension H01631 Acute heart failure H01633 High blood[genome.jp]
  • Long term obstructed respiration can lead to pulmonary hypertension, which in turn can cause right ventricular hypertrophy and ultimately lead to decompensation.[docplayer.net]
  • Due to hypoplastic lungs, there is frequently pulmonary hypertension leading to right-to-left shunting and progressive hypoxemia, hypercarbia, and acidosis that worsens the pulmonary hypertension.[pongpdf.com]
Heart Failure
  • failure H01633 High blood pressure Respiratory diseases Lung diseases H00904 Cutis laxa with severe pulmonary, gastrointestinal, and urinary abnormalities H00830 Alveolar capillary dysplasia with misalignment of pulmonary veins H01103 Alpha-1-antitrypsin[genome.jp]
  • It could be the result of vascular injury, arrhythmia, insufflating too much carbon dioxide, impending heart failure, gas embolism or the development of a pneumothorax.[pongpdf.com]
  • […] disease H01626 Arteriosclerosis obliterans H01629 Chronic arterial occlusive disease H01630 Patent ductus arteriosus [PATH: hsa04270 ] H01620 Raynaud syndrome H01658 Microscopic polyangiitis H01687 Extrahepatic portal vein obstruction H01723 Deep vein thrombosis[genome.jp]
  • There has also been a report of prenatal ulceration of the tongue due to natal teeth58. The lesion begins as an ulcerated area and with repeated trauma it may progress to an enlarged fibrous mass with the appearance of a granuloma.[vdocuments.mx]
  • There has also been a report of prenatal ulceration of the tongue due to natal teeth 58. The lesion begins as an ulcerated area and with repeated trauma it may progress to an enlarged fibrous mass with the appearance of a granuloma.[datenpdf.com]
  • H01782 Eosinophilic gastrointestinal disorder H01853 Chronic nonspecific multiple ulcers of the small intestine H01871 Isolated hypoganglionosis H01874 Cronkhite-Canada syndrome H01901 Barrett esophagus H02122 Chronic atrial and intestinal dysrhythmia[genome.jp]
  • Clinical manifestations can range from intestinal obstruction, abdominal pain, GI bleeding, ulceration, or mediastinal compression.[pongpdf.com]
  • […] syndrome 2 * Duane-radial ray syndrome * Dubin-Johnson syndrome * Dubowitz syndrome * Duchenne muscular dystrophy * Duhring Brocq disease * Duhring's disease * Duker Weiss Siber syndrome * Duodenal atresia * Duodenal atresia tetralogy of Fallot * Duodenal ulcer[medicalgeek.com]
  • Infrequent parietal foramina, delayed bone age, and increased fracture frequency are reported.[docplayer.net]
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  • Seronegative arthritis H01532 Gout [PATH: hsa00230 ] H01604 Polymyositis and dermatomyositis H01606 Polymyalgia rheumatica H01636 Fibromyalgia H01693 Eosinophilic fasciitis H02089 Winchester syndrome H02238 Spinal muscular atrophy with congenital bone fractures[genome.jp]
  • Generally the avascular splenophrenic and colic ligaments are cauterized, the short gastric and hilar vessels are individually ligated with metallic clips or gastrointestinal staplers, and the spleen is placed in a plastic bag, fracture or morzelized[pongpdf.com]
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  • […] syndrome H01004 Velocardiofacial syndrome H01223 Mental retardation-stereotypic movements-epilepsy and/or cerebral malformations H01238 Phelan-McDermid syndrome [PATH: hsa04724 ] H01790 Emanuel syndrome H01791 Smith-Magenis syndrome H01731 Fragile X tremor[genome.jp]


The triggers of this syndrome remain unknown, so the diagnosis is based on the presence of characteristic clinical findings.

  • IPO is only to be diagnosed after mechanical causes of intestinal obstruction have been ruled out, which is generally done by means of imaging studies [2]. Blood samples, biopsy specimens and possibly other materials should be analyzed to reveal any underlying disease that may cause secondary pseudo-obstruction, and any suspicion on drug-induced motility disorders should be followed up. For detailed instructions concerning the workup of suspected IPO, the interested reader is referred to evidence and consensus-based recommendations available elsewhere [3]. With regard to the present cases, Harris and colleagues noted a decrease in serum and erythrocyte cholinesterase levels shortly before the younger brother died. Histological studies carried out on gastrointestinal tissue samples of both patients yielded few significant findings, namely ulceration of the gastric cardia and infiltration of the terminal ileum by inflammatory cells, each in one of the boys [1]. Furthermore, post-mortem examinations of the children revealed dense intra-abdominal adhesions, small bowel dilation, and microcolon.
  • Abnormal findings in clinical examination and auscultation should prompt a thorough cardiological assessment. Vascular anomalies are best displayed by echocardiography, which allows for the confirmation of the suspected diagnosis and the measurement of PDA size, the volume of diverted blood, flow direction and velocity [4]. Harris et al. heard characteristic systolic murmurs in both children and confirmed the diagnosis of PDA by electrocardiography and cardiac catheterization, but these techniques are no longer part of the recommended approach to diagnosis [5].
  • NT are teeth that are present at birth. They should be differentiated from neonatal teeth that erupt during the first month of life and are diagnosed on sight.

Although hematological abnormalities were not reported by Harris et al., the possibility of large-platelet thrombocytopenia occurring in the setting of this syndrome shall be mentioned. This, based on a publication by FitzPatrick and colleagues, who wrote about three male relatives with IPO and PDA [6]. Additional findings described in these patients were dysmorphic facial features, infantile esotropia, atrial septal defect, hydronephrosis, and cryptorchidism. It has not yet been clarified whether both families were affected by the same disease, but targeted investigations of possible future cases may shed some light on this issue. In this context, genetic studies should also be carried out to confirm the presence or absence of FLNA mutations [7].


Only symptomatic treatment can be provided to affected individuals and must address IPO, PDA, and NT individually.

Treatment of IPO is challenging and requires a multidisciplinary effort combining nutritional, surgical, and pharmacological therapies. Nutritional support aims at the restoration of water and electrolyte balance and the maintenance of an adequate caloric intake. Oral food intake is preferred over enteral nutrition with feeding tubes if the patient is able to eat by mouth. In most cases, however, parenteral nutrition becomes necessary, and patients need to be closely monitored for complications such as liver failure, thrombosis, infection, and sepsis [2]. In fact, one of the patients characterized by Harris et al. died of sepsis related to parenteral nutrition [1]. One way to minimize complications of parenteral nutrition and to concomitantly relieve symptoms is surgery. Its role in IPO management, however, has long since been disputed: It is not curative of the disease and is associated with considerable morbidity and mortality. So when to revert to surgery? Venting ostomy placement may be indicated when the decompression of distended gastrointestinal segments can no longer be realized by nasogastric or rectal tubes or endoscopically [8]. Also, surgical interventions may be required in emergency situations, and comorbidities such as diaphragmatic hernia may imply the need for surgery independent of IPO [1]. Both nutritional support and surgical treatment are generally complemented with pharmacological therapies. Prokinetics, antiemetics, and analgesics are most commonly applied to this end, and small intestinal bacterial overgrowth may be prevented by non-absorbable antibiotics [8]. Finally, serious complications of any of the aforementioned treatment strategies and poor quality of life on standard regimens are indications to intestinal or multivisceral transplantation [2].

The surgical ligation of PDA is performed in case of cardiac dysfunction or respiratory failure, as described by Harris et al. [1]. Their patient did not respond to pharmacological treatment, which likely consisted in the intravenous or oral administration of indomethacin, ibuprofen, or acetaminophen. Asymptomatic or mildly symptomatic PDA warrant a conservative approach and may close spontaneously [5].

Supernumerary NT or teeth that are loose, pose a risk of injury to intraoral tissues, or interfere with breastfeeding should be removed. Otherwise, no treatment is necessary [9].


Both children described in the original case report succumbed to their disease. One of the boys died at the age of 6 weeks, the other one lived to be five months old. The older brother died despite repeated surgery for IPO and PDA ligation [1].

Considered individually, neither of the conditions defining this syndrome is universally lethal. The combination of IPO and PDA has later been said to "have a good prognosis with supportive therapy" [6], and treatment options have definitely improved since the 1970s. Notwithstanding, IPO is still related to mortality rates of up to 30% and is associated with significant morbidity [3]. It may require lifelong treatment to increase intestinal motility, control abdominal pain, and meet the nutritional needs of the patient, or intestinal transplantation. Its profound impact on life quality is undeniable and confirmed by the high rates of suicide of IPO patients [10].

Generally speaking, PDA has an excellent prognosis in term infants with normal birth weights [11]. The health and immunological status of patients with IPO, however, may negatively affect the outcome. Available literature contains descriptions of four IPO patients who underwent PDA ligation, namely the two brothers described by Harris et al. - who died of IPO complications - and the two male children presented by FitzPatrick and colleagues - who recovered well [1] [6].

NT don't usually pose a serious health problem as long as aspiration is avoided [9].


The fact that two siblings presented with identical signs and symptoms is highly suggestive of a genetic disorder. Yet, the underlying mutation remains unknown. The authors of the original case report proposed an X-linked recessive pattern of inheritance, whereby this hypothesis is built on vague claims regarding the patients' family history. In detail, the patients' mother had four sisters but no brothers, and her mother was one of seven with only one male surviving infancy. These observations are in agreement with the presence of an X-linked lethal factor, although the possibility of coincidence as an explanation for this particular distribution of sexes should not be neglected. In this line, autosomal recessive inheritance is also plausible [1].

Congenital IPO has been related to distinct gene defects and environmental influences. On the one hand, IPO is known to be part of different mitochondrial disorders, where gastrointestinal complaints are generally most prominent. Mitochondrial neurogastrointestinal encephalomyopathy is one of these disorders [12]. IPO has also been linked to mutations of genes L1CAM, RAD21, ACTG2, and SOX10, which give rise to complex conditions such as hydrocephalus with congenital idiopathic IPO, Mungan syndrome, visceral myopathy, and Waardenburg syndrome [2]. All of these conditions are rare and differ considerably from the disease described in this article, but there's a single case report that may be of increased interest here: Two brothers and a maternal uncle have been diagnosed with familial IPO and PDA, and there are numerous similarities between the patients described in that publication - who have been diagnosed with X-linked chronic idiopathic neuronal IPO - and those presented by Harris and colleagues [1] [6]. X-linked chronic idiopathic neuronal IPO has later been associated with mutations of the FLNA gene, which encodes for filamin A [7], and it would be intriguing to see whether there are female carriers of a pathogenic FLNA variant among surviving members of the index family.

With regard to environmental factors inducing IPO, prenatal exposure to alcohol has been named as a possible cause [13]. However, there is no indication that the two boys described by Harris et al. would have been exposed to the toxic effects of alcohol.


Data regarding the epidemiology of congenital IPO are scarce, which is at least partly due to the lack of specific diagnostic criteria. One of the few studies available has been carried out in the United States and suggests its incidence to be approximately 1 in 40,000 live births [3]. The vast majority of cases is sporadic, with familial cases accounting for 3-17% of all cases, according to different authors [14] [15]. The boys with IPO, PDA, and NT, as described by Harris and coworkers, fall into this category. They were born to healthy, non-consanguineous parents in the United States [1]. To date, they remain the only patients ever reported with this particular phenotype. It should be noted, though, that there are single case reports describing largely similar conditions that may or may not correspond to the same entity [6] [16]. Either way, the co-occurrence of IPO and PDA continues to be an exceedingly rare event.

Sex distribution
Age distribution


The pathogenetic mechanisms leading to syndromic IPO, PDA, and NT remain poorly understood. This is primarily due to knowledge gaps regarding the etiology of the disease. If one assumed this syndrome to be related to mutations of the FLNA gene, as is X-linked chronic idiopathic neuronal IPO, some general statements could be made.

Filamin A is a large cytoskeletal protein that cross-links the actin cytoskeleton into orthogonal networks and modulates the cellular response to chemical and mechanical environmental factors by regulating changes in their shape and motility [7]. Furthermore, neuronal intestinal dysplasia could be demonstrated by the histopathological examination of biopsy specimens obtained from one of the patients with X-linked chronic idiopathic neuronal IPO [6]. Loss-of-function FLNA mutations may thus entail abnormalities of the cytoskeleton of enteric neurons, interfere with their structure and function, and induce neuronal IPO [7].


No recommendations can be given to prevent this rare syndrome and prenatal diagnoses are not yet feasible. Notwithstanding, male children born to mothers who are known to carry the causal gene defect may benefit from close monitoring from birth.


In 1976, Harris and colleagues reported the unusual co-occurrence of IPO, PDA, and NT [1]. Additional cases have not been described to date, although there was at least one more family - this one from Scotland - with a genetic predisposition to IPO and PDA [6]. The Scottish patients presented with IPO, PDA, and large-platelet thrombocytopenia, and the authors pointed out that IPO and large-platelet thrombocytopenia had been observed in yet another, unrelated patient, who was attended in England [16]. Finally, X-linked IPO has been reported in Italy, although neither PDA nor thrombocytopenia has been noted in this case [7] [17]. It cannot currently be confirmed if all these cases or at least part of them correspond to the same entity, which is why the present article focuses on the original case report by Harris et al.

Patient Information

Natal teeth (NT), patent ductus arteriosus (PDA), and intestinal pseudo-obstruction (IPO) have been described as a rare syndrome in the newborn:

  • NT are teeth that are present at birth. They don't usually pose a serious health problem but may need to be removed so as not to damage the baby's tongue or interfere with breastfeeding.
  • PDA is a rather common and treatable heart defect. Failure of ductus closure allows for a left-to-right shunt to form between the aorta and pulmonary artery. According to the size of the ductus and the symptoms displayed by the patient, the physician may choose a conservative approach, pharmacological or surgical treatment. In general, patients recover very well.
  • IPO is the most serious condition observed in this syndrome. It refers to the absence of gastrointestinal motility, i.e., the digestive tract is unable to push the food forward. Treatment requires a multidisciplinary effort combining nutritional, surgical, and pharmacological therapies, and may be needed throughout life. The outcome is uncertain.



  1. Harris DJ, Ashcraft KW, Beatty EC, Holder TM, Leonidas JC. Natal teeth, patent ductus arteriosus and intestinal pseudo-obstruction: a lethal syndrome in the newborn. Clin Genet. 1976; 9(5):479-482.
  2. Di Nardo G, Di Lorenzo C, Lauro A, et al. Chronic intestinal pseudo-obstruction in children and adults: diagnosis and therapeutic options. Neurogastroenterol Motil. 2017; 29(1).
  3. Thapar N, Saliakellis E, Benninga MA, et al. Paediatric Intestinal Pseudo-obstruction: Evidence and Consensus-based Recommendations From an ESPGHAN-Led Expert Group. J Pediatr Gastroenterol Nutr. 2018; 66(6):991-1019.
  4. Evans N. Diagnosis of the preterm patent ductus arteriosus: clinical signs, biomarkers, or ultrasound? Semin Perinatol. 2012; 36(2):114-122.
  5. Gillam-Krakauer M, Reese J. Diagnosis and Management of Patent Ductus Arteriosus. Neoreviews. 2018; 19(7):e394-e402.
  6. FitzPatrick DR, Strain L, Thomas AE, et al. Neurogenic chronic idiopathic intestinal pseudo-obstruction, patent ductus arteriosus, and thrombocytopenia segregating as an X linked recessive disorder. J Med Genet. 1997; 34(8):666-669.
  7. Gargiulo A, Auricchio R, Barone MV, et al. Filamin A is mutated in X-linked chronic idiopathic intestinal pseudo-obstruction with central nervous system involvement. Am J Hum Genet. 2007; 80(4):751-758.
  8. Lauro A, De Giorgio R, Pinna AD. Advancement in the clinical management of intestinal pseudo-obstruction. Expert Rev Gastroenterol Hepatol. 2015; 9(2):197-208.
  9. Leung AK, Robson WL. Natal teeth: a review. J Natl Med Assoc. 2006; 98(2):226-228.
  10. Lindberg G, Iwarzon M, Tornblom H. Clinical features and long-term survival in chronic intestinal pseudo-obstruction and enteric dysmotility. Scand J Gastroenterol. 2009; 44(6):692-699.
  11. Jansen EJS, Dijkman KP, van Lingen RA, et al. Using benchmarking to identify inter-centre differences in persistent ductus arteriosus treatment: can we improve outcome? Cardiol Young. 2017; 27(8):1488-1496.
  12. Erdogan MA, Seckin Y, Harputluoglu MM, et al. A mitochondrial neurogastrointestinal encephalomyopathy with intestinal pseudo-obstruction resulted from a novel splice site mutation. Clin Dysmorphol. 2019; 28(1):22-25.
  13. Uc A, Vasiliauskas E, Piccoli DA, Flores AF, Di Lorenzo C, Hyman PE. Chronic intestinal pseudoobstruction associated with fetal alcohol syndrome. Dig Dis Sci. 1997; 42(6):1163-1167.
  14. Di Lorenzo C. Pseudo-obstruction: current approaches. Gastroenterology. 1999; 116(4):980-987.
  15. Vargas JH, Sachs P, Ament ME. Chronic intestinal pseudo-obstruction syndrome in pediatrics. Results of a national survey by members of the North American Society of Pediatric Gastroenterology and Nutrition. J Pediatr Gastroenterol Nutr. 1988; 7(3):323-332.
  16. Pollock I, Holmes SJ, Patton MA, Hamilton PA, Stacey TE. Congenital intestinal pseudo-obstruction associated with a giant platelet disorder. J Med Genet. 1991; 28(7):495-496.
  17. Auricchio A, Brancolini V, Casari G, et al. The locus for a novel syndromic form of neuronal intestinal pseudoobstruction maps to Xq28. Am J Hum Genet. 1996; 58(4):743-748.

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Last updated: 2019-07-21 06:17