A rare cause of anaemia associated with hypertension in a 14-year-old girl

We report a rare example of anaemia and hypertension due to an incomplete Carney triad in a 14-year-old girl with no previous medical history. This rare non-familial syndrome generally involves two disparate tumours: gastrointestinal stromal tumour, paraganglioma and/or pulmonary chondroma. The complete triad is a syndrome that involves at least five loci: stomach, oeophagus, lung, the paraganglionic system, adrenal (cortex or medulla). The pathogenesis is unclear as these tumours have different embryological origins. Surgical treatment is necessary, and long-term follow-up is advisable as patients with Carney triad may re-present with tumour(s), even several years after the first presentation.     

Gastrointestinal stromal tumors (GIST) in children and adolescents: A comprehensive review of the current literature

Standards for the management of gastrointestinal stromal tumors (GIST) in children do presently not exist. Thus a systematic review and summary of the current literature was conducted serving as a basis for the further development of optimal management strategies for childhood GIST within a cooperative network. Presently 21 cases with familial GIST, and more than 100 pediatric cases each with Carney triad or sporadic GIST have been published so far. An international prospective registration based on national registries has recently started to acquire more clinical and molecular data and to develop appropriate management strategies for children and adolescents with GIST. Pediatr Blood Cancer 2009; 53:1171–1179. © 2009 Wiley‐Liss, Inc.     

Carney Complex Presenting with Raynaud’s Phenomenon and Erythematous Macules of the Extremities

A 12-year-old male presented with a 6-week history of apparent digital vasculitis with color changes of the distal fingers and erythematous macules of the palms and soles. Physical examination revealed skin findings of Carney complex and an abnormal cardiac examination. Echocardiography demonstrated a large left atrial mass, which caused partial obstruction during diastole and moderate mitral valve insufficiency. Surgical excision and pathological examination of the mass confirmed the presence of a large, peduculated myxoma. This case illustrates the presentation of Carney complex with left atrial myxoma as apparent vasculitis and Raynaud’s phenomenon.     

GENETICS OF CARNEY COMPLEX AND RELATED FAMILIAL LENTIGINOSES, AND OTHER MULTIPLE TUMOR SYNDROMES

Carney complex is a multiple endocrine neoplasia (MEN) syndrome that affects the adrenal cortex, the pituitary and thyroid glands, and the gonads. The complex is also associated with skin and mucosa pigmentation abnormalities and myxoid and other neoplasms of mesenchymal and neural crest origin. Thus, this syndrome also belongs to another group of genetic disorders, the lentiginoses (or lentigenoses), which include the Peutz-Jeghers, LEOPARD, arterial dissections and lentiginosis, and Laugier-Hunziker syndromes, Cowden disease and Ruvalcaba-Myhre-Smith (Bannayan-Zonana) syndrome and the centrofacial, benign patterned and segmental lentiginoses, all of which can be associated with a variety of developmental defects. The inheritance of Carney complex, just like that of the other MENs and the lentiginoses, is autosomal dominant. Genetic loci or genes have been identified for Carney complex, Peutz-Jeghers and Ruvalcaba-Myhre-Smith syndromes, but not for other lentiginoses. Elucidation of the molecular defects responsible for these disorders is expected to shed light on aspects of early neural crest differentiation, the regulation of pigmentation, the development of autonomous endocrine function, and endocrine and nonendocrine tumorigenesis.     

Cutaneous signs are important in the diagnosis of the rare neoplasia syndrome Carney complex

We describe a 15-year-old boy who presented with a stroke. Brain MRI imaging showed thalamic and multiple cerebral infarcts. An echocardiogram revealed multiple atrial masses, which were resected. Histological examination confirmed multiple atrial myxomas. Further clinical examination of the patient revealed subtle buccal and peri-oral lentigenes. The diagnosis of Carney complex was made clinically. The patient was subsequently diagnosed with testicular seminomas and a cutaneous angiomyxoma. Genetic investigation revealed a pathological mutation in the PRKAR1A gene. We review the reported manifestations and presentations of Carney complex, along with current diagnostic guidelines. We emphasise the importance of recognising the cutaneous manifestations of this rare autosomal dominantly inherited neoplasia syndrome.     

Clinical, radiological, and pathological findings in four children with gastrointestinal stromal tumors of the stomach

The incidence of gastrointestinal stromal tumors (GISTs) in children is exceptionally low. However, during the last decade these tumors attracted increasing attention, because they were found to express the cell surface transmembrane receptor kit (CD117) that has tyrosine kinase activity. This tyrosine kinase can be semi-selectively inhibited by signal transduction inhibitors such as imatinib mesylate (Glivec), which is a competitive inhibitor of c-kit, c-abl, platelet-derived growth factor receptor-alpha (PDGFR-alpha) and PDGFR-beta, and abl-related gene (arg). The authors present the clinical, radiographic, and pathological findings of 4 children who were diagnosed with gastric GIST. One of them had an incomplete Carney triad including GIST and mediastinal paraganglioma. All 4 patients presented with anemia and anemia-related symptoms and underwent total resection of the tumor. One patient received additional chemotherapy (in the pre-imatinib era) and 2 patients received a short course of imatinib mesylate. With a follow-up of 116, 55, 23, and 10 months all patients are alive in first complete continuous remission. In children and adolescents, particularly in female patients, GISTs should be included in the differential diagnosis of anemia secondary to gastrointestinal hemorrhage. Complete surgical resection is the mainstay of treatment for this tumor, with imatinib mesylate restricted to patients with advanced or metastatic tumors. Since late recurrences (up to 30 years following initial diagnosis) are reported, a life-long follow-up is mandatory in these patients.     

A concise genetic and clinical guide to multiple endocrine neoplasias and related syndromes

Several familial neoplastic syndromes are associated with endocrine gland oncogenesis. The main ones are: multiple endocrine neoplasia type 1 (MEN 1), which affects primarily the pituitary, pancreas, and parathyroid glands; MEN 2A and MEN 2B, which involve mainly the thyroid and parathyroid glands and the adrenal medulla; familial medullary thyroid carcinoma (FMTC), which affects only the thyroid gland; and, finally, Carney complex, which affects the adrenal cortex, pituitary, thyroid gland, and the gonads. Carney complex is also associated with pigmentation abnormalities and myxoid and other neoplasms of mesenchymal origin. Thus, this syndrome also belongs to another group of genetic disorders, those associated with pigmentation defects and multiple tumors, including tumors of the endocrine glands. Peutz-Jeghers syndrome and Cowden disease are just two of these disorders that have recently been elucidated at the molecular level. von Hippel-Lindau disease is another condition that affects the pancreas and adrenal medulla and its gene is also known. The inheritance of the MENs, Carney complex, and related syndromes is autosomal dominant. Clinical recognition of these syndromes at a young age improves clinical outcome and prognosis of the various tumors and decreases associated morbidity and mortality. This review considers a wider, more inclusive view of the MEN syndromes, summarizes their clinical features and presents the newest information on their molecular elucidation.     

Prolactin secretion abnormalities in patients with the "syndrome of spotty skin pigmentation, myxomas, endocrine overactivity and schwannomas" (Carney complex)

Carney complex is a multiple neoplasia and lentiginosis syndrome. Acromegaly due to growth hormone (GH)-producing adenomas has been considered the only pituitary-related manifestation of the complex. In the present study, seven patients with Carney complex, who belonged to three unrelated kindreds and had relatives with acromegaly, were investigated for the presence of GH and prolactin (PRL) secretion abnormalities (familial cases). In addition, four patients with the complex and no family history of the complex were studied (sporadic cases). Seven of the patients were female and four were male; their mean age was 24.27 +/- 4.34 years. Sampling every 20 min for one hour in the morning and under fasting and unstimulated conditions was performed in all patients, for determination of serum PRL levels. Insulin-like growth factor-I (IGF-I) levels and magnetic resonance imaging (MRI) of the pituitary were also obtained. Patients who had elevated IGF-I levels underwent investigation for acromegaly by oral glucose tolerance test and thyrotropin-releasing hormone. Seven of the 11 patients (63.6%) had moderately high PRL levels (mean Z score value 2.12 +/- 0.66); three of these patients also had elevated IGF-I levels but a negative investigation for acromegaly. All patients had negative pituitary MRI. The patient with the highest PRL levels underwent 24-hour sampling every 20 min, which demonstrated a higher baseline secretion of this hormone with preservation of its circadian pulsatility. Hyperprolactinemia was present in two siblings and a parent-child pair. We conclude that prolactin hypersecretion, albeit mild, appears to be frequent in patients with Carney complex, is inherited in an autosomal dominant manner in kindreds with the syndrome, and may be associated with elevated IGF-I levels in some, but not all, patients.     

Primary cardiac tumors associated with genetic syndromes: a comprehensive review

Various cardiac tumors occur in the setting of a genetic syndrome such as myxomas in Carney complex and rhabdomyomas in tuberous sclerosis. Tumor biology can be different in syndromic forms, and on imaging children sometimes demonstrate additional manifestations of the underlying syndrome. We discuss the imaging appearance of cardiac tumors occurring in the framework of a genetic syndrome, the findings that suggest an underlying syndrome, and the impact on management.     

Typical and atypical Carney's triad presenting with malignant hypertension and papilledema

This report encourages clinicians to consider a diagnosis of Carney's triad in patients with multifocal gastric stromal sarcoma, extraadrenal paraganglioma (predominantly mediastinal), or pulmonary chondroma. The authors conducted a retrospective 20-year survey at the Hospital for Sick Children and identified two children with Carney's triad. One child, presenting atypically with papilledema and fundal hemorrhages from malignant hypertension and benign intracranial hypertension from chronic iron-deficiency anemia, is the second patient ever to date be described with the complete Carney's triad of neoplasms at diagnosis. Another child presented more typically with gastric stromal sarcoma and pulmonary chondroma without paraganglioma. Carney's triad is a rare differential diagnosis for "idiopathic" hypertension or iron-deficiency anemia from chronic gastrointestinal bleeding. If missed, patients with Carney's triad may have the debilitating physical and mental consequences of chronic iron deficiency and may die of untreated prolonged hypertension and metastatic leiomyosarcoma.     

Monosomy 7, Diabetes Insipidus and Acute Myeloid Leukemia in Childhood

The triad of diabetes insipidus (DI), monosomy 7, and acute myeloid leukemia in a 7—year old boy is described. This triad has been described in adults but not in children. The DI ran a transient, self-limiting course and required no specific therapy. The pathogenesis of DI remains unknown, and its transient nature may result in this component of the triad going unnoticed.     

Chromosomal imbalance in the Aniridia-Wilms' tumor association: 11p interstitial deletion.

The triad of aniridia, ambiguous genitalia, and mental retardation (AGR triad) is the characteristic clinical feature of three unrelated patients with previously unreported chromosome 11 short arm interstitial deletions. A Wilms' tumor in one patient establishes one cause for the aniridia-Wilms' tumor association. The genetic heterogeneity of aniridia, the AGR triad, and Wilms' tumor are demonstrated, and Wilms' tumor is indicated to be a neoplastic birth defect which can result from a variety of embryologic insults, some of which may be chromosomal or heritable.     

Carney's triad: Apropos of a new case

Carney's triad is defined by the coexistence of at least two of three rare disorders, including gastric epithelioid leiomyosarcoma (malignant leiomyoblastoma), pulmonary chondroma, and paraganglioma, most often extra-adrenal and functioning. We report a new case in a 10-year-old girl. The paraganglioma, although nonfunctioning, was detected after it was searched for, as Carney's triad was suspected. Unrelated seems the development of breast fibroadenomas in the same patient. Whenever a patient with one component of the triad is encountered, the possibility of this syndrome should be considered and the other two components sought.     

Biliary atresia: making the diagnosis by the gallbladder ghost triad

OBJECTIVE: To describe the gallbladder ghost triad and evaluate its usefulness in the sonographic diagnosis of extrahepatic biliary atresia (BA). METHODS: From October 1997 to February 2002, 217 fasted infants with cholestatic jaundice aged 2-12 weeks were examined sonographically. We defined the gallbladder ghost triad as gallbladder length <1.9 cm, lack of smooth/complete echogenic mucosal lining with an indistinct wall and irregular/lobular contour, and used it as a criteria for BA. Gallbladder wall thickness, triangular cord, diffuse periportal echogenicity and hepatic artery calibre were also recorded. Diagnosis of BA was confirmed surgically and histologically. RESULTS: Thirty of 31 babies with BA demonstrated the gallbladder ghost triad. No false-positives were recorded. The 31st BA baby showed a normal gallbladder at 6 weeks, but developed the ghost triad at 8 weeks. Gallbladder wall thickening was seen in 46/186 non-BA babies, but not in BA. Triangular cord was observed in 24/31 babies. Twenty-two of 186 non-BA babies and 5/31 BA babies showed diffuse periportal echogenicity. The hepatic artery appeared more prominent in BA. All 31 babies diagnosed sonographically as BA had surgery. Three non-BA babies had "negative" laparotomies showing hypoplastic bile ducts. CONCLUSIONS: The gallbladder ghost triad is a very accurate sign of BA. Indeterminate cases require close follow-up.     

MRI and radiographic findings in Currarino's triad

Currarino's triad is a rare complex of a congenital sacral bony abnormality, anorectal malformation and a presacral mass. Intractable constipation since birth is the leading symptom of this triad, which follows an autosomal dominant mode of heredity. We report conventional radiographic and MR findings in one family consisting of a mother and her two daughters. In all three cases, radiography revealed an abnormality of the os sacrum, the so-called scimitar sacrum. MR examination, undertaken next in our institution, was applied with T1-, T2- and proton density weighted sequences in all three orientations before and after i. v. application of gadolinium diethylene-triamine-pentaacetic acid (Gd-DTPA). In two patients we were able to diagnose the complete form of the triad and in one patient an incomplete form. In any case of a radiographically diagnosed scimitar sacrum in combination with constipation, Currarino's triad should be considered. MRI, as the method of choice, should be the next step to detect a presacral mass and any anomalies of the spinal canal. The importance of early recognition lies in the high morbidity and mortality rates resulting from this disorder.     

Insufficient evidence for ‘shaken baby syndrome’ – a systematic review

Shaken baby syndrome has typically been associated with findings of subdural haematoma, retinal haemorrhages and encephalopathy, which are referred to as the triad. During the last decade, however, the certainty with which the triad can indicate that an infant has been violently shaken has been increasingly questioned. The aim of this study was to determine the diagnostic accuracy of the triad in detecting that an infant had been shaken. The literature search was performed using PubMed, Embase and the Cochrane Library up to October 15, 2015. Relevant publications were assessed for the risk of bias using the QUADAS tool and were classified as having a low, moderate or high risk of bias according to predefined criteria. The reference standards were confessions or witnessed cases of shaking or accidents. The search generated 3773 abstracts, 1064 were assessed as possibly relevant and read as full texts, and 30 studies were ultimately included. Of these, 28 were assessed as having a high risk of bias, which was associated with methodological shortcomings as well as circular reasoning when classifying shaken baby cases and controls. The two studies with a moderate risk of bias used confessions and convictions when classifying shaken baby cases, but their different designs made a meta‐analysis impossible. None of the studies had a low risk of bias. Conclusion: The systematic review indicates that there is insufficient scientific evidence on which to assess the diagnostic accuracy of the triad in identifying traumatic shaking (very low‐quality evidence). It was also demonstrated that there is limited scientific evidence that the triad and therefore its components can be associated with traumatic shaking (low‐quality evidence).     

Autism: research into causes and intervention

Autism spectrum conditions are neuro-developmental syndromes with strong heritability. Cognitive theories have had some success in explaining why the cluster of features should co-occur. Empathizing deficits have the potential to make sense of one triad of impairments (social difficulties, communication difficulties and imagining others' minds), and may have a brain basis in the amygdala and left medial frontal cortex. A strong systemizing drive may account for a distinct triad of strengths (good attention to detail, deep, narrow interests and islets of ability). The brain basis of systemizing is yet to be understood. Family genetics studies suggest that these same cognitive dimensions (reduced empathizing alongside a strong drive to systemize) may also characterize the 'broader phenotype' among first-degree relatives. Molecular genetic studies are underway and any candidate genes for autism will ultimately need to be tested in relation to the observed differences in the brain, cognition and behaviour. The ethics of genetic screening or gene therapy should be thought about well ahead of these becoming available, since there is by no means any consensus that these would be desirable given the wide range of phenotypic traits, not all of which are disabling. Future research will need to focus on evaluating the extent to which any form of intervention reduces the triad of impairments whilst supporting the triad of strengths.     

The Currarino triad: complex of anorectal malformation,sacral bony abnormality,and presacral mass

The Currarino triad is a unique complex of congenital caudal anomalies including anorectal malformation, sacral bony abnormality, and presacral mass. The usual symptomatology is constipation due to anorectal stenosis. Contrast enema and computed tomographic myelography are the imaging modalities of choice for diagnostic confirmation and clarification of the anomalies. The clinical features, unique radiologic appearance, and importance of a correct diagnosis of the Currarino triad are reviewed.     

Magnetic resonance detection of myelodysplasia in children with Currarino triad

Purpose. To evaluate the role of MRI in the detection of myelodysplasia in children with Currarino triad. Materials and methods. Six patients (two girls, four boys, aged 7 months–14 years, mean age 6 years) were studied with MRI, voiding cystourethrogram and barium enema or fistulography. CT and ultrasonography were also performed in two patients. Results. All patients presented with partial agenesis of the sacrum. Three patients suffered from an intermediate form of anorectal malformation (ARM) and three had a high form of ARM. The presacral masses consistent with Currarino triad included anterior meningocoele in three patients, lipoma in two patients and anterior lipomeningocoele in one patient. MRI diagnosed tethering of the spinal cord in four of six patients. The tethering of the spinal cord was due to a lipomeningocoele in one patient, an intradural lipoma in one patient and a lipoma of the filum in two patients. Conclusion. The association of Currarino triad with tethered spinal cord seems more common than generally reported in the literature. Preoperative MRI of the lumbosacral spine is essential to detect significant myelodysplasia in all patients with Currarino triad. Received: 15 January 1997 Accepted: 23 June 1997