Pineocytoma in a child with Pallister-Killian syndrome: a case report and review of the literature.

Pallister-Killian syndrome (PKS; OMIM #601803) is a rare genetic disorder typically characterized by developmental delay, seizures, sparse temporal hair, and facial dysmorphisms. PKS is most frequently caused by mosaic supernumerary isochromosome 12p. Here, we report a 27-month-old girl with a prenatal diagnosis of PKS and a histopathological diagnosis of pineocytoma.

Human Genetics of Ventricular Septal Defect.

Ventricular septal defects (VSDs) are recognized as one of the commonest congenital heart diseases (CHD), accounting for up to 40% of all cardiac malformations, and occur as isolated CHDs as well as together with other cardiac and extracardiac congenital malformations in individual patients and families. The genetic etiology of VSD is complex and extraordinarily heterogeneous. Chromosomal abnormalities such as aneuploidy and structural variations as well as rare point mutations in various genes have been reported to be associated with this cardiac defect. This includes both well-defined syndromes with known genetic cause (e.g., DiGeorge syndrome and Holt-Oram syndrome) and so far undefined syndromic forms characterized by unspecific symptoms. Mutations in genes encoding cardiac transcription factors (e.g., NKX2-5 and GATA4) and signaling molecules (e.g., CFC1) have been most frequently found in VSD cases. Moreover, new high-resolution methods such as comparative genomic hybridization enabled the discovery of a high number of different copy number variations, leading to gain or loss of chromosomal regions often containing multiple genes, in patients with VSD. In this chapter, we will describe the broad genetic heterogeneity observed in VSD patients considering recent advances in this field.

Extracorporeal Membrane Oxygenation (ECMO) for suspected neonatal genetic diagnoses with cardiorespiratory failure.

Recent data describe an increasing use of extracorporeal membrane oxygenation (ECMO) in neonates with various clinical conditions besides primary respiratory or cardiac diagnoses. Infants with underlying genetic disorders characterized by cardiopulmonary failure pose unique management challenges. When pathognomonic dysmorphic features for common genetic diagnoses are not present, the prognosis is uncertain at best when determining ECMO candidacy. Lengthy turnaround times of genetic testing often delay definitive diagnosis during the ECMO course. Clinical management pathways to guide practice and evidence to support the use of ECMO in rare genetic conditions are lacking. The decision to initiate ECMO is daunting but may be of benefit if the subsequent genetic diagnosis is non-lethal. In lethal genetic cases warranting discontinuation of care, the time spent on ECMO may still be advantageous as a bridge to diagnosis while allowing for parental bonding with the terminally ill infant. Diagnostic confirmation may also facilitate the attainment of closure for these parents. Here, we report our experience providing ECMO to three neonates presenting with cardiorespiratory failure and later diagnosed with rare genetic syndromes. We share the challenges faced, lessons learned, and outcomes of these critically ill neonates.

[Atypical presentation of a polyp of Killian]. / Cas clinique. Présentation atypique d'un polype de Killian.

The antrochoanal polyp or polyp of Killian is a benign nasal tumour that arises from the maxillary sinus. The polyp originating from the middle turbinate is an entity rarely described in the literature. We report here a rare case of Killian polyp originating from the middle turbinate which was explored by computed tomography and magnetic resonance imaging of the facial bone. The polyp was removed by an endoscopic surgical technique. The extraction was made from the oropharynx. Preoperative recognition of these anatomical variations is particularly important to avoid intraoperative surprises.

Le polype antro-choanal ou polype de Killian est une tumeur bénigne naso-sinusienne qui prend naissance au niveau du sinus maxillaire. Le polype provenant du cornet moyen est une entité rarement décrite dans la littérature. Nous rapportons ici un cas rare de polype choanal provenant du cornet moyen qui a été exploré par tomodensitométrie et par résonance magnétique du massif facial. Le polype été retiré par une technique de chirurgie endoscopique. L'extraction a été réalisée à partir de l'oropharynx. La reconnaissance préopératoire de ces variations anatomiques est particulièrement importante pour éviter les surprises peropératoires.

Cellular and Biochemical Characterization of Mesenchymal Stem Cells from Killian Nasal Polyp.

Killian's (antrochoanal) polyp is a unilateral nasal polypoid lesion of the maxillary sinus especially affecting children and young adults with unilateral nasal obstruction, pus discharge, and headache. Although its etiology is unclear, chronic inflammation, autoreactivity, allergies, and viral infections are implicated in its formation and development, causing nasal tissue remodeling. In this context, we isolated and cultured mesenchymal stem cells from surgical biopsies of three patients with Killian nasal polyp (KNP-MSCs) while healthy nasal tissue (HNT-MSCs) was used as control. Our results demonstrated that KNP-MSCs exhibited reduced cell proliferation compared to HNT-MSCs, and migrated less than the control, showing a partial epithelial phenotype with low mRNA levels of I-CAM and a significant increase of E-cad. Subsequently, both MSCs were induced to osteoblastic or adipocyte differentiation for up to 20 days. KNP-MSCs underwent to differentiate into osteoblasts but exhibited reduced ALP activity and calcium deposits and low mRNA levels of osteogenesis-associated genes compared to osteogenic induced-HNT-MSCs. Conversely, KNP-MSCs and HNT-MSCs have shown the same adipogenic differentiation potential, with a similar lipid droplet amount, adipocyte gene expression, and triacylglycerols content. Taken together, these results first demonstrated the cellular and molecular characterization of MSCs derived from the Killian nasal polyp.

Prenatal diagnosis of Pallister-Killian syndrome and literature review.

Pallister-Killian syndrome (PKS) is a rare sporadic genetic disorder usually caused by mosaicism of an extra isochromosome of 12p (i(12p)). This retrospective study analysed the prenatal ultrasound manifestations and molecular and cytogenetic results of five PKS foetuses. Samples of amniotic fluid and/or cord blood, skin biopsy and placenta were collected. Conventional karyotyping and single nucleotide polymorphism array (SNP array) were performed on all the amniotic fluid or cord blood samples. Copy number variants sequencing (CNV-seq) and fluorescence in situ hybridization (FISH) were also used for the validation for one foetus. All the five foetuses were from pregnancies with advanced parental age. Two foetuses involved structural abnormalities and one foetus had only soft markers, all of which included increased nuchal translucency. The rest two foetuses had normal ultrasounds in the second trimester, which has rarely been reported before. The karyotype revealed typical i(12p) in four cases and a small supernumerary marker chromosome consisting of 12p and 20p in the remaining one case. The proportion of cells with i(12p) ranged from 0 to 100% in cultural cells, while SNP array results suggested 2-4 copies of 12p. For one foetus, metaphase FISH showed normal results, but the interphase FISH suggested cell lines with two, three and four copies of 12p in the amniotic fluid. Advanced parental age may be an important risk factor for PKS, and there were no typical ultrasound manifestations related to PKS. A combination of karyotype analysis and molecular diagnosis is an effective method for the diagnosis of PKS.

Ultrasonographic characteristics of Killian-Jamieson diverticula.

PURPOSE: A Killian-Jamieson diverticulum (KJD) may be mistaken for a thyroid nodule on ultrasound (US). The purpose of this retrospective study was to search for specific US features that would help differentiate between KJD and thyroid nodules. METHODS: A total of 12 patients with KJD who had undergone an US examination of the neck were identified. The size, shape, boundary, echopattern, location, color flow signals on color Doppler US of KJD and the relationship between the lesion and esophageal wall were analyzed. The change of size, shape and internal echotexture were also observed when the lesion was compressed with the probe and when the patient was asked to drink water. RESULTS: All KJD were confirmed by barium esophagography. All KJD were posterior to the left thyroid lobe on US, and were associated with a semicircular hypoechoic anterior wall. The internal echotexture was heterogeneous. In eight cases, the connection to the esophageal wall was seen. When compressing with the US probe or when the patients swallowed water, the size, shape or internal echotexture of the lesion changed. CONCLUSION: The specific criteria for US diagnosis of KJD included the connection to the esophageal wall and the fact that the internal echotexture, shape and size of KJD changed in real-time when the patient swallowed water or when the lesion was compressed with the transducer.

Is nasogastric tube feeding necessary after hypopharyngeal diverticulum surgery?

OBJECTIVES: Nasogastric tubes (NGT) are often placed after surgery for cricopharyngeal muscle pathology due to risk of infection and mediastinitis. The aim of this study was to examine if this practice is necessary. METHODS: A retrospective case series of subjects who underwent surgery for hypopharyngeal diverticula or cricopharyngeal bars from March 2011 to June 2018 was conducted. Demographic data, type of surgery, placement of feeding tube, initiation of oral feeding, and any complications were recorded. RESULTS: Sixty-four surgeries were performed for Zenker's diverticula (ZD; N = 52), Killian-Jamieson diverticula (N = 2), and cricopharyngeal bar (N = 10). Mean age and ZD pouch size were 74.0 ± 10.6 years and 3.1 ± 1.8 cm, respectively. Procedures included 48 carbon dioxide laser-assisted myotomies, 14 open diverticulectomies, and 2 endoscopic stapler-assisted diverticulotomies. Of the 64 patients, 19 (29.7%) received intraoperative NGTs while the remaining 45 (70.3%) did not receive NGTs. The former cohort had the NGTs removed on post-operative day (POD) 4.5 ± 2.5, and the non-NGT cohort started clear liquid diet (CLD) on POD 1.2 ± 0.7 days, where 38 patients (84.4%) started CLD on POD 1, and 5 patients (7.8%) were started on oral diet on POD 2-4. Over time, fewer NGTs were placed and oral diets were started sooner. There were 5 complications occurring in 3 patients from the NGT cohort (15.5%) and 2 from the non-NGT cohort (4.4%). CONCLUSIONS: Surgery for hypopharyngeal diverticula and CPB may not require routine perioperative NGT placement which can be associated with higher rates of complication. Patients can safely receive CLD on POD 1.

De l'histoire des chirurgiens cachés derrière nos instruments du quotidien. Partie 4 : la rhinoplastie.

Many surgical instruments are named after their inventors, acclaimed surgeons of the past, because of their discoveries and their contributions in the field of surgical techniques. However, these daily reminders of history of surgery are often forgotten by the modern practitioners. We propose to review, through a selection of instruments, short biographies of these precursors. This fourth original article will focus on the inventors of rhinoplasty instruments: Joseph, Killian, Aufricht, Cottle and Claoué.

Pallister-Killian syndrome: Review of fetal phenotype.

Pallister-Killian syndrome is a multi-system sporadic disorder with developmental delay. It is a rare chromosomal abnormality involving supernumerary isochormosome 12p. The disorder exhibits tissue specific mosaicism. The first prenatal diagnosis of PKS was reported in 1985 after ultrasound detection of fetal anomalies. Since this observation, there have been about 62 reports of fetuses with PKS. In this review, we cover the prenatal aspects of PKS.

Ductus Venosus Agenesis as a Marker of Pallister-Killian Syndrome.

The ductus venosus (DV) is a shunt that allows the direct flow of well-oxygenated blood from the umbilical vein (UV) to the coronary and cerebral circulation through the foramen ovale. Its agenesis has been associated with chromosomal abnormalities and rare genetic syndromes, structural defects, intrauterine growth restriction (IUGR) and even antepartum fetal demise. Pallister-Killian Syndrome (PKS) is a rare sporadic disorder with specific tissue mosaic distribution of an extra 12p isochromosome (i(12p)). Its main clinical features are moderate to severe intellectual disability/neuromotor delay, skin pigmentation abnormalities, typical facial appearance, variable association with multiple congenital malformations and epilepsy. Though prenatal findings (including congenital diaphragmatic hernia, ventriculomegaly, congenital heart disease, polyhydramnios, and rhizomelic shortening) have been described in literature, prenatal diagnosis is difficult as there are no associated identification signs no distinctive or pathognomonic signs, and some of these malformations are hard to identify prenatally. The tissue mosaicism linked to this syndrome and the decrease of the abnormal clone carrier of the i(p12) after successive trypsinizations of cultured cells makes the diagnosis even more challenging. We present the case of a 27.5 weeks pregnant woman with a fetal ductus venosus agenesis (DVA) as the main guide marker. To our knowledge this is the first case published in literature reporting a DVA as a guide sign to diagnose a complex condition as Pallister-Killian syndrome. We also underscore the key role of new genetic techniques as microarrays to avoid misdiagnosis when only a subtle sonographic sign is present in complex conditions like this.

Next generation phenotyping in Emanuel and Pallister-Killian syndrome using computer-aided facial dysmorphology analysis of 2D photos.

High throughput approaches are continuously progressing and have become a major part of clinical diagnostics. Still, the critical process of detailed phenotyping and gathering clinical information has not changed much in the last decades. Forms of next generation phenotyping (NGP) are needed to increase further the value of any kind of genetic approaches, including timely consideration of (molecular) cytogenetics during the diagnostic quest. As NGP we used in this study the facial dysmorphology novel analysis (FDNA) technology to automatically identify facial phenotypes associated with Emanuel (ES) and Pallister-Killian Syndrome (PKS) from 2D facial photos. The comparison between ES or PKS and normal individuals expressed a full separation between the cohorts. Our results show that NPG is able to help in the clinic, and could reduce the time patients spend in diagnostic odyssey. It also helps to differentiate ES or PKS from each other and other patients with small supernumerary marker chromosomes, especially in countries with no access to more sophisticated genetic approaches apart from banding cytogenetics. Inclusion of more facial pictures of patient with sSMC, like isochromosome-18p-, cat-eye-syndrome or others may contribute to higher detection rates in future.

Prenatal profile of Pallister-Killian syndrome: Retrospective analysis of 114 pregnancies, literature review and approach to prenatal diagnosis.

Pallister-Killian syndrome (PKS) is a tissue limited mosaic disorder, characterized by variable degrees of neurodevelopmental delay and intellectual disability, typical craniofacial findings, skin pigmentation anomalies and multiple congenital malformations. The wide phenotypic spectrum of PKS in conjunction with the mosaic distribution of the i(12p) makes PKS an underdiagnosed disorder. Recognition of prenatal findings that should raise a suspicion of PKS is complicated by the fragmentation of data currently available in the literature and challenges in diagnosing a mosaic diagnosis on prenatal testing. Ultrasound anomalies, especially congenital diaphragmatic hernia, congenital heart defects, and rhizomelic limb shortening, have been related to PKS, but they are singularly not specific and are not present in all affected fetuses. We have combined prenatal data from 86 previously published reports and from our cohort of 114 PKS probands (retrospectively reviewed). Summarizing this data we have defined a prenatal growth profile and identified markers of perinatal outcome which collectively provide guidelines for early recognition of the distinctive prenatal profile and consideration of a diagnosis of PKS as well as for management and genetic counseling.

[Prenatally diagnosed case of Pallister‒Killian syndrome]. / Praenatalisan diagnosztizált Pallister­Killian-szindróma esete.

Pallister-Killian syndrome (PKS) is a rare, sporadic genetic disorder that is caused by the mosaic presence of a supernumerary marker chromosome, isochromosome 12p. The syndrome is a polydysmorphic condition characterized by mental retardation, craniofacial dysmorphism, hypotonia, seizures, epilepsy and certain organic malformations (diaphragmatic hernia, congenital heart disease). Prenatal diagnosis is challenging due to the mosaic tissue-specific distribution of the chromosomal disorder and highly variable phenotype. Prenatal diagnosis is often accidental, however, appropriate laboratory techniques based on the second trimester ultrasound anomalies provide accurate prenatal diagnosis. We report a case of a 36-year-old primipara with second trimester ultrasound markers (polyhydramnion, ventriculomegaly, rhizomelic micromelia, abnormal facial profile). The patient underwent amniocentesis, the conventional karyotyping revealed a supernumerary chromosome in nearly 50 percent of amniocytes. FISH and targeted multicolour FISH probes verified mosaic tetrasomy of the short arm of chromosome 12 of the fetus. Fetopathological examinations and analysis of fetal tissues and blood confirmed the prenatal diagnosis. To our knowledge, this is the first reported case of prenatally diagnosed Pallister-Killian syndrome in Hungary. Orv Hetil. 2018; 159(21): 847-852.

Unclassifiable pattern of hypopigmentation in a patient with mosaic partial 12p tetrasomy without Pallister-Killian syndrome.

Pallister-Killian syndrome (PKS-#OMIM601803) is a multisystem developmental disorder typically due to the presence of an aneuploidy cell line, consisting of a supernumerary tetrasomic chromosomal marker (SCM) arisen from the short arm of chromosome 12 (12p isochromosome). The clinical phenotype, which is strictly related to the percentage and tissue distribution of aneuploid cells, is characterized by craniofacial dysmorphisms, pigmentary skin anomalies, limb shortening, congenital heart defects, diaphragmatic hernia, hypotonia, intellectual disability, and epilepsy. We report on a 4 year-old girl harboring a 12p partial isochromosome, involving the PKS critical region, affecting about 70% of circulating lymphocytes, urine, and saliva cells and fibroblast from a hyperpigmented skin spot, and 100% of fibroblasts from a hypopigmented skin spot. Interestingly, despite the high proportion of affected cells this patient did not present with PKS, and a pattern of linear and patchy pigmentary mosaicism was the sole clinical manifestation. The present observation suggests that partial 12p SCM can also result in mild phenotypes, and its prevalence in the human population could have been underestimated. Accurate dermatologic evaluation could be a major handle for genetic testing.

[Hans Franz Edmund Killian - nestor of German anesthesia : Critical appraisal on the 125th anniversary of his birth]. / Hans Franz Edmund Killian ­ Nestor der deutschen Anästhesie : Kritische Würdigung zum 125. Geburtstag.

The surgeon Hans Killian was born on 5 August 1892 in Freiburg im Breisgau, Germany. Together with the pharmacologist Hellmut Weese and the surgeon Helmut Schmidt he was one of the nestors of modern German anesthesia. Early on during his scientific and clinical career, he addressed problems of surgical anesthesia and in 1928 he became one of the editors of the first German journal of anesthesia Narcosis and Anesthesia ("Narkose und Anästhesie"). In 1934 he published the textbook Anesthesia for Surgical Purposes ("Narkose zu operativen Zwecken"). Between World Wars I and II, he campaigned for anesthesia to become an independent medical discipline comparable to the situation in the Anglo-Saxon countries at that time. Because of his merits in the foundation of the German Society of Anesthesia on 10 April 1953 he became its first honorary member. Killian died on 7 March 1982 in Freiburg, Germany. Excerpts of his autobiography which he wrote a few years before his death and which were part of his inheritance are published here for the first time.

Oro-dental features of Pallister-Killian syndrome: Evaluation of 21 European probands.

Pallister-Killian syndrome (PKS) is a rare sporadic multi-systemic developmental disorder caused by a mosaic tetrasomy of the short arm of chromosome 12. A wide range of clinical characteristics including intellectual disability, seizures, and congenital malformations has previously been described. Individuals with PKS show a characteristic facial phenotype with frontal bossing, alopecia, sparse eyebrows, depressed nasal bridge, long philtrum, telecanthus, and posteriorly rotated ears. Oro-dental features, such as "Pallister lip," macroglossia, delayed eruption of primary teeth, high arched-palate, prognathism, and cleft palate have been occasionally reported in the medical literature. The aim of the study was to assess the oro-dental phenotype of PKS and to describe the oral health status in a cohort participating in the First European Workshop on PKS. A clinical dental examination was performed in 21 Caucasian probands and data regarding medical and dental history collected. Twelve probands (57%) showed an atypical dental pattern, with multiple missing teeth (primarily the first permanent molars) and 2 (10%) a double teeth. The severity of gingivitis and dental caries increased with age and gingival overgrowth was a common finding. A characteristic occlusive phenotype was found: a high-arched palate with mandibular prognathism associated with an anterior openbite and crossbite and with posterior crossbite (unilateral or bilateral). The prevalence of oral habits (non-nutritive sucking, mouth breathing, bruxism) was high, even in older probands. This study suggests that individuals affected by PKS should be observed closely for oro-dental diseases and a multidisciplinary approach is needed to implement the right preventive measures. © 2016 Wiley Periodicals, Inc.

Clinical Conundrum: Killian-Jamieson Diverticulum with Paraesophageal Hernia.

Killian-Jamieson diverticulum is a outpouching of the lateral cervical esophageal wall adjacent to the insertion of the recurrent laryngeal to the larynx and is much less common in clinical practice than Zenkers Diverticulum. Surgical management of Killian-Jamieson diverticulum requires open transcervical diverticulectomy due to the proximity of the recurrent laryngeal nerve to the base of the pouch. We present a case of a Killian-Jamieson diverticulum associated with a concurrent large type III paraesophageal hernia causing significant solid-food dysphagia, post-prandial regurgitation of solid foods, and chronic cough managed with open transcervical diverticulectomy and laparoscopic paraesophageal hernia repair with Nissen fundoplication.

Rigid endoscopic LASER diverticulotomy for lateral pharyngoesophageal diverticuli: cases presentation and discussion.

Killian-Jamieson diverticulum (KJD) is a rare cervical esophageal abnormality. Transcervical approach has been the main treatment modality to prevent recurrent laryngeal nerve (RLN) injury. We presented two cases of patients confirmed with KJD and were managed successfully under rigid endoscope. The new technique and idea were described in detail. Under rigid laryngoscope, the septum between the true esophagus lumen and diverticulum can be exposed clearly. A microscope equipped with CO2 LASER system offered precise and focused point cutting energy to the septum. Several efforts were applied to prevent RLN injury in the cases descriptions. We use transnasal esophagoscope and eating assessment tool (EAT-10) for anatomic and functional result evaluation. Much improved symptoms of dysphagia and intact RLN function were observed. Under the assist of rigid laryngoscope and point-cutting CO2 LASER, KJD diverticulotomy could be performed safely with little complication for patients refusing transcervical route.

Anatomy of trisomy 12.

Trisomy 12 is a rare aneuploidy and fetuses with this defect tend to spontaneously abort. However, mosaicism allows this anomaly to manifest itself in live births. Due to the fact that mosaicism represents a common genetic abnormality, trisomy 12 is encountered more frequently than expected at a rate of 1 in 500 live births. Thus, it is imperative that medical practitioners are aware of this aneuploidy. Moreover, this genetic disorder may result from a complete or partial duplication of chromosome 12. A partial duplication may refer to a specific segment on the chromosome, or one of the arms. On the other hand, a complete duplication refers to duplication of both arms of chromosome 12. The combination of mosaicism and the variable duplication sites has led to variable phenotypes ranging from normal phenotype to Potter sequence to gross physical defects of the various organ systems. This article provides a review of the common anatomical variation of the different types of trisomy 12. This review revealed that further documentation is needed for trisomy 12q and complete trisomy 12 to clearly delineate the constellation of anomalies that characterize each genetic defect. Clin. Anat. 29:633-637, 2016. © 2016 Wiley Periodicals, Inc.