Japanese familial anetoderma: A report of two cases and review of the published work.

J Dermatol. 2018 Dec;45(12):1459-1462

Authors: Fukayama M, Miyagaki T, Akamata K, Suzuki S, Tanaka M, Sato S

Abstract
Anetoderma is a rare cutaneous disorder characterized by focal loss of dermal elastic tissue, resulting in macular atrophy or herniated saclike skin. Some families with hereditary anetoderma have been described, but there have been no reports on Japanese familial anetoderma so far. We herein report two Japanese sibling cases of primary anetoderma. A healthy 13-year-old Japanese girl and a healthy 15-year-old Japanese girl presented to our hospital with a 6-month history of small atrophic pittings on their arms and trunks. All lesions were less than 0.5 cm in diameter, which are relatively small for non-familial anetoderma. Preceding infections or skin lesions were not observed. A skin biopsy revealed a focal, complete loss of elastic tissue in the superficial to mid-dermis which was surrounded by fine, irregular or twisted elastic fibers. Based on these findings, the diagnosis of anetoderma was made. Review of published works demonstrated that the mode of inheritance of familial anetoderma is not simple, suggesting that it is important to survey any family member of the patients with anetoderma.

PMID: 30320485 [PubMed - indexed for MEDLINE]

Urine oligosaccharide screening by MALDI-TOF for the identification of NGLY1 deficiency.

Mol Genet Metab. 2018 05;124(1):82-86

Authors: Hall PL, Lam C, Alexander JJ, Asif G, Berry GT, Ferreira C, Freeze HH, Gahl WA, Nickander KK, Sharer JD, Watson CM, Wolfe L, Raymond KM

Abstract
N-glycanase deficiency (NGLY1 deficiency, NGLY1-CDDG), the first autosomal recessive congenital disorder of N-linked deglycosylation (CDDG), is caused by pathogenic variants in NGLY1. The majority of affected individuals have been identified using exome or genome sequencing. To date, no reliable, clinically available biomarkers have been identified. Urine oligosaccharide analysis was included as part of a routine evaluation for possible biomarkers in patients with confirmed NGLY1-CDDG. During the qualitative review of oligosaccharide profiles by an experienced laboratory director an abnormal analyte with a proposed structure of Neu5Ac1Hex1GlcNAc1-Asn was identified in NGLY1-CDDG patient urine samples. The same species has been observed in profiles from individuals affected with aspartylglucosaminuria, although the complete spectra are not identical. Additional studies using tandem mass spectrometry confirmed the analyte's structure. In addition to the known NGLY1-CDDG patients identified by this analysis, a single case was identified in a population referred for clinical testing who subsequently had a diagnosis of NGLY1-CDDG confirmed by molecular testing. Urine oligosaccharide screening by MALDI-TOF MS can identify individuals with NGLY1-CDDG. In addition, this potential biomarker might also be used to monitor the effectiveness of therapeutic options as they become available.

PMID: 29550355 [PubMed - indexed for MEDLINE]

[Tarsal Kink: Pathognomonic Presentation and Therapy of a Rare Congenital Upper Eyelid Malformation].

Klin Monbl Augenheilkd. 2018 Jan;235(1):34-38

Authors: Schaudig U, Keserü M

Abstract
BACKGROUND: Presentation of a congenital abnormality that is rare, but follows a distinct course and can be diagnosed and cured promptly if the pathognomonic presentation is recognized. A congenital tarsal kink leads to a malposition of the upper eyelid margin that must not be missed, as it will lead to ulcerative keratitis if it is not treated.
CASE PRESENTATION: An otherwise healthy newborn was presented after delivery with forceps with marked unilateral purulent secretion and blepharospasm.
DIFFERENTIAL DIAGNOSIS: Neonatal dacryocystitis, gonococcal infection, congenital entropion with ulcerative keratitis, tarsal kink.
EXAMINATION: It was not possible to fully examine the lid and cornea with the baby awake. Due to total inversion of the lid margin, no lashes could be seen. Under general anesthesia, the tarsal kink, with complete inversion of the lid margin and a corneal ulcer, was confirmed.
TREATMENT: The literature offers several methods to correct this rare malposition, all of which aim to strengthen the anterior lamella to correct the kink. After incision of the kink and repositioning of the tarsus and securing the position with fixation sutures, the ulcer healed quickly and completely; lid closure and lid contour were normal and symmetrical.
SUMMARY: Complete inversion of the lid margin is the pathognomonic sign of tarsal kink, giving the impression of "missing" lashes, accompanied by blepharospasm, followed by purulent secretion and corneal ulceration. The condition must not be misdiagnosed as only immediate correction can prevent severe damage.

PMID: 29373869 [PubMed - indexed for MEDLINE]

7 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2019/04/04

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

7 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2019/04/04

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Aberrant regulation of epigenetic modifiers contributes to the pathogenesis in patients with selenoprotein N-related myopathies.

Hum Mutat. 2019 Apr 01;:

Authors: Bachmann C, Noreen F, Voermans NC, Schär PL, Vissing J, Fock JM, Bulk S, Kusters B, Moore SA, Beggs AH, Mathews KD, Meyer M, Genetti CA, Meola G, Cardani R, Mathews E, Jungbluth H, Muntoni F, Zorzato F, Treves S

Abstract
Congenital myopathies are early onset, slowly progressive neuromuscular disorders of variable severity. They are genetically and phenotypically heterogeneous and caused by pathogenic variants in several genes. Multi-minicore Disease, one of the more common congenital myopathies, is frequently caused by recessive variants in either SELENON, encoding the endoplasmic reticulum glycoprotein selenoprotein N or RYR1, encoding a protein involved in calcium homeostasis and excitation-contraction coupling. The mechanism by which recessive SELENON variants cause Multiminicore disease (MmD) is unclear. Here, we extensively investigated muscle physiological, biochemical and epigenetic modifications, including DNA methylation, histone modification, and noncoding RNA expression, to understand the pathomechanism of MmD. We identified biochemical changes that are common in patients harboring recessive RYR1 and SELENON variants, including depletion of transcripts encoding proteins involved in skeletal muscle calcium homeostasis, increased levels of Class II histone deacetylases (HDACs) and DNA methyltransferases. CpG methylation analysis of genomic DNA of patients with RYR1 and SELENON variants identified >3,500 common aberrantly methylated genes, many of which are involved in calcium signaling. These results provide the proof of concept for the potential use of drugs targeting HDACs and DNA methyltransferases to treat patients with specific forms of congenital myopathies.

PMID: 30932294 [PubMed - as supplied by publisher]

The Pediatric Cell Atlas: Defining the Growth Phase of Human Development at Single-Cell Resolution.

Dev Cell. 2019 Mar 27;:

Authors: Taylor DM, Aronow BJ, Tan K, Bernt K, Salomonis N, Greene CS, Frolova A, Henrickson SE, Wells A, Pei L, Jaiswal JK, Whitsett J, Hamilton KE, MacParland SA, Kelsen J, Heuckeroth RO, Potter SS, Vella LA, Terry NA, Ghanem LR, Kennedy BC, Helbig I, Sullivan KE, Castelo-Soccio L, Kreigstein A, Herse F, Nawijn MC, Koppelman GH, Haendel M, Harris NL, Rokita JL, Zhang Y, Regev A, Rozenblatt-Rosen O, Rood JE, Tickle TL, Vento-Tormo R, Alimohamed S, Lek M, Mar JC, Loomes KM, Barrett DM, Uapinyoying P, Beggs AH, Agrawal PB, Chen YW, Muir AB, Garmire LX, Snapper SB, Nazarian J, Seeholzer SH, Fazelinia H, Singh LN, Faryabi RB, Raman P, Dawany N, Xie HM, Devkota B, Diskin SJ, Anderson SA, Rappaport EF, Peranteau W, Wikenheiser-Brokamp KA, Teichmann S, Wallace D, Peng T, Ding YY, Kim MS, Xing Y, Kong SW, Bönnemann CG, Mandl KD, White PS

Abstract
Single-cell gene expression analyses of mammalian tissues have uncovered profound stage-specific molecular regulatory phenomena that have changed the understanding of unique cell types and signaling pathways critical for lineage determination, morphogenesis, and growth. We discuss here the case for a Pediatric Cell Atlas as part of the Human Cell Atlas consortium to provide single-cell profiles and spatial characterization of gene expression across human tissues and organs. Such data will complement adult and developmentally focused HCA projects to provide a rich cytogenomic framework for understanding not only pediatric health and disease but also environmental and genetic impacts across the human lifespan.

PMID: 30930166 [PubMed - as supplied by publisher]

Potential application of ultrasound-guided thermal ablation in rare liver tumors.

Hepatobiliary Pancreat Dis Int. 2018 Dec;17(6):531-537

Authors: Wu LL, Chen JX, Li K, Su ZZ, Long YL, Luo LP, Xu EJ, Zheng RQ

Abstract
BACKGROUND: With the advances of imaging techniques, the detection rate of rare liver tumor is increased. However, the therapeutic strategies of the rare liver tumors remain limited.
METHODS: We analyzed twelve pathologically confirmed rare liver tumors in 8 patients. All of the patients underwent ultrasound (US) guided biopsy and subsequent thermal ablation. The tumors were ablated according to the preoperative plans and monitored by real-time US. CT/MRI fused with contrast enhanced US (CEUS) or three-dimensional (3D) US-CEUS images were used to guide and assess the ablation zone more accurately during thermal ablation. The rate of technical efficacy was assessed based on the contrast-enhance CT/MRI (CECT/MRI) results one month after ablation. Local tumor progression (LTP), recurrence and complications were followed up and recorded.
RESULTS: Among these twelve nodules, nine were subject to US-guided thermal ablation, whereas the other three inconspicuous nodules were subject to CEUS-guided thermal ablation. Intra-procedure CT/MRI-CEUS or 3D US-CEUS fusion imaging assessments demonstrated that the ablation zone sufficiently covered the original tumor, and no immediate supplementary ablation was required. Additionally, no major complications were observed during the follow-up period. The postoperative CECT/MRI confirmed that the technique success rate was 100%. Within the surveillance period of 13 months, no LTP or recurrence was noted.
CONCLUSIONS: US-guided thermal ablation was feasible and safe for rare liver tumors. The use of fusion imaging technique might make US-guided thermal ablation as effective as surgical resection, and this technique might serve as a potential therapeutic modality for rare liver tumors in the future.

PMID: 30424963 [PubMed - indexed for MEDLINE]

Mastozytose - Pathogenese, Klinik und Therapie.

J Dtsch Dermatol Ges. 2018 Jan;16(1):42-59

Authors: Wagner N, Staubach P

PMID: 29314684 [PubMed - indexed for MEDLINE]

Clinically Integrated Molecular Diagnostics in Adenoid Cystic Carcinoma.

Oncologist. 2019 Mar 29;:

Authors: Thierauf J, Ramamurthy N, Jo VY, Robinson H, Frazier RP, Gonzalez J, Pacula M, Dominguez Meneses E, Nose V, Nardi V, Dias-Santagata D, Le LP, Lin DT, Faquin WC, Wirth LJ, Hess J, Iafrate AJ, Lennerz JK

Abstract
BACKGROUND: Adenoid cystic carcinoma (ACC) is an aggressive salivary gland malignancy without effective systemic therapies. Delineation of molecular profiles in ACC has led to an increased number of biomarker-stratified clinical trials; however, the clinical utility and U.S.-centric financial sustainability of integrated next-generation sequencing (NGS) in routine practice has, to our knowledge, not been assessed.
MATERIALS AND METHODS: In our practice, NGS genotyping was implemented at the discretion of the primary clinician. We combined NGS-based mutation and fusion detection, with MYB break-apart fluorescent in situ hybridization (FISH) and MYB immunohistochemistry. Utility was defined as the fraction of patients with tumors harboring alterations that are potentially amenable to targeted therapies. Financial sustainability was assessed using the fraction of global reimbursement.
RESULTS: Among 181 consecutive ACC cases (2011-2018), prospective genotyping was performed in 11% (n = 20/181; n = 8 nonresectable). Testing identified 5/20 (25%) NOTCH1 aberrations, 6/20 (30%) MYB-NFIB fusions (all confirmed by FISH), and 2/20 (10%) MYBL1-NFIB fusions. Overall, these three alterations (MYB/MYBL1/NOTCH1) made up 65% of patients, and this subset had a more aggressive course with significantly shorter progression-free survival. In 75% (n = 6/8) of nonresectable patients, we detected potentially actionable alterations. Financial analysis of the global charges, including NGS codes, indicated 63% reimbursement, which is in line with national (U.S.-based) and international levels of reimbursement CONCLUSION: Prospective routine clinical genotyping in ACC can identify clinically relevant subsets of patients and is approaching financial sustainability. Demonstrating clinical utility and financial sustainability in an orphan disease (ACC) requires a multiyear and multidimensional program.
IMPLICATIONS FOR PRACTICE: Delineation of molecular profiles in adenoid cystic carcinoma (ACC) has been accomplished in the research setting; however, the ability to identify relevant patient subsets in clinical practice has not been assessed. This work presents an approach to perform integrated molecular genotyping of patients with ACC with nonresectable, recurrent, or systemic disease. It was determined that 75% of nonresectable patients harbor potentially actionable alterations and that 63% of charges are reimbursed. This report outlines that orphan diseases such as ACC require a multiyear, multidimensional program to demonstrate utility in clinical practice.

PMID: 30926674 [PubMed - as supplied by publisher]

Incidence of rare cancers in the city of São Paulo, Brazil.

Tumori. 2019 Feb;105(1):22-30

Authors: Bustamante-Teixeira MT, Latorre MDRDO, Guerra MR, Tanaka LF, Botta L, Trama A, Gatta G

Abstract
INTRODUCTION:: Rare cancers are a challenge for clinical practice as well as for epidemiology and public health. Studies on this subject are few and limited to the study of cases with scarce epidemiologic information. This study aimed to evaluate the incidence of rare cancers and to compare the demographic, anatomic, and histologic characteristics of rare and nonrare (common) cancers.
METHODS:: Incidence data were obtained from the Population-based Cancer Registry of São Paulo, Brazil. Rare neoplasms were those defined in the RARECARE list, which takes into account an incidence lower than 6/100,000/year.
RESULTS:: In São Paulo, 20.4% of tumors had an incidence lower than 6/100,000/year from 1997 to 2012, being therefore considered as rare tumors. We identified 11 entities with an incidence greater than 6/100,000/year (common neoplasms) and 186 entities with an incidence lower than 6/100,000/year (rare neoplasms). The mean annual incidence of all cancers was 365 per 100,000 in São Paulo between 1997 and 2012, and the incidence of all rare tumors was 74.5 per 100,000.
CONCLUSIONS:: This study presents the burden of rare cancers in Brazil. It is expected to be an incentive for further studies of these entities in order to know the epidemiologic profile of rare tumors in Brazil and to provide a more effective diagnostic and therapeutic approach.

PMID: 30700226 [PubMed - indexed for MEDLINE]

[Parsonage-Turner Syndrome - Case Report].

Z Orthop Unfall. 2017 Dec;155(6):705-707

Authors: Katzer A, Niedermauntel WP, Rump J

Abstract
Neuralgic amyotrophy of the shoulder (Parsonage-Turner syndrome) is a rare condition of unknown aetiology which manifests as acute neuropathy of the brachial plexus. Diagnosis is based on typical symptoms and physical examination. In addition, magnetic resonance imaging of the affected shoulder and the cervical spine is advisable, in order to distinguish this syndrome from other conditions with similar symptoms. There is no specific treatment for neuralgic amyotrophy, but in about 50 - 67% of cases complete recovery occurs within two to three years, depending on the severity of the symptoms when they first appear. In patients whose strength and function are not fully restored, neurological deficits may remain, especially if the same shoulder is affected by recurrent attacks.

PMID: 28926848 [PubMed - indexed for MEDLINE]

6 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2019/03/29

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

6 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2019/03/29

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Impaired human hematopoiesis due to a cryptic intronic GATA1 splicing mutation.

J Exp Med. 2019 Mar 26;:

Authors: Abdulhay NJ, Fiorini C, Verboon JM, Ludwig LS, Ulirsch JC, Zieger B, Lareau CA, Mi X, Roy A, Obeng EA, Erlacher M, Gupta N, Gabriel SB, Ebert BL, Niemeyer CM, Khoriaty RN, Ancliff P, Gazda HT, Wlodarski MW, Sankaran VG

Abstract
Studies of allelic variation underlying genetic blood disorders have provided important insights into human hematopoiesis. Most often, the identified pathogenic mutations result in loss-of-function or missense changes. However, assessing the pathogenicity of noncoding variants can be challenging. Here, we characterize two unrelated patients with a distinct presentation of dyserythropoietic anemia and other impairments in hematopoiesis associated with an intronic mutation in GATA1 that is 24 nucleotides upstream of the canonical splice acceptor site. Functional studies demonstrate that this single-nucleotide alteration leads to reduced canonical splicing and increased use of an alternative splice acceptor site that causes a partial intron retention event. The resultant altered GATA1 contains a five-amino acid insertion at the C-terminus of the C-terminal zinc finger and has no observable activity. Collectively, our results demonstrate how altered splicing of GATA1, which reduces levels of the normal form of this master transcription factor, can result in distinct changes in human hematopoiesis.

PMID: 30914438 [PubMed - as supplied by publisher]

Pediatric Nasoorbitoethmoid Fractures: Cause, Classification, and Management.

Plast Reconstr Surg. 2019 01;143(1):211-222

Authors: Lopez J, Luck JD, Faateh M, Macmillan A, Yang R, Siegel G, Susarla SM, Wang H, Nam AJ, Milton J, Grant MP, Redett R, Tufaro AP, Kumar AR, Manson PN, Dorafshar AH

Abstract
BACKGROUND: Currently, there is a paucity of information on the presentation and proper management of pediatric nasoorbitoethmoid fractures. The purpose of this study was to examine the incidence, cause, associated injuries, and management of these fractures. Furthermore, the authors sought to assess outcomes after transnasal wiring or suture canthopexy for type III nasoorbitoethmoid fractures.
METHODS: A retrospective cohort review was performed of all patients with nasoorbitoethmoid fractures who presented to a Level I trauma center from 1990 to 2010. Charts and computed tomographic imaging were reviewed, and nasoorbitoethmoid fractures were labeled based on the Markowitz-Manson classification system. Patient fracture patterns, demographics, characteristics, and outcomes were recorded. Univariate and multivariate methods were used to compare groups.
RESULTS: A total of 63 pediatric patients were identified in the study period. The sample's mean age was 8.78 ± 4.08 years, and 28.6 percent were girls. The sample included 18 type I injuries, 28 type II injuries, and 17 type III injuries. No significant demographic differences were found between patients with type I, II, and III fractures (p > 0.05). Operative intervention was pursued in 16.7, 46.4, and 82.4 percent of type I, II, and III nasoorbitoethmoid fractures, respectively. In patients with type III nasoorbitoethmoid fractures, no patients with transnasal wiring developed telecanthus.
CONCLUSIONS: Pediatric nasoorbitoethmoid fractures are uncommon injuries. Type I fracture can often be treated with close observation. However, type II and III injury patterns should be evaluated for operative intervention. Transnasal wiring is an effective method to prevent traumatic telecanthus deformity in type III fracture patterns.

PMID: 30589796 [PubMed - indexed for MEDLINE]

Acquired diffuse slate-grey facial dyspigmentation due to henna: an unrecognized cause of pigment contact dermatitis in Korean patients.

Eur J Dermatol. 2018 Oct 01;28(5):644-648

Authors: Woo YR, Kim JS, Lim JH, Choi JY, Kim M, Yu DS, Park YM, Park HJ

Abstract
Henna is a vegetable hair dye that can be used by individuals who are sensitized to oxidative dyes due to low allergenicity. The reported incidence of slate-grey facial dyspigmentation following the use of henna hair dye is extremely rare. This study aimed to identify the clinical, dermoscopic, and histopathological features of slate-grey facial dyspigmentation following the use of henna hair dye in Korean patients. We identified all patients who presented with slate-grey facial dyspigmentation following usage of henna hair dye. Patients were further evaluated for clinical, dermoscopic, and histopathological findings along with their patch test results. All 11 patients were females with Fitzpatrick's skin phototype III or IV. Prominent slate-grey-coloured dyspigmentation on the lateral side of the face and neck was most common in eight (72%) patients. Under dermoscopic examination, a pseudo-network with grey dots was observed in all patients. Histopathological examination revealed liquefaction degeneration of the epidermal basal layer and pigmentary incontinence in the papillary dermis in all patients. The diagnosis of pigmented contact dermatitis following usage of henna was made based on the clinical, dermoscopic, and histopathological findings in all patients. Pigmented contact dermatitis associated with henna occurs mostly in middle-aged women and requires long-term treatment. Therefore, careful attention should be paid when henna is used to dye hair in this age group.

PMID: 30530434 [PubMed - indexed for MEDLINE]

Gorlin-Goltz syndrome: a case series from north Italy.

Eur J Dermatol. 2018 Oct 01;28(5):687-688

Authors: Veronese F, Miglino B, Boggio P, Tiberio R, Zavattaro E, Colombo E, Savoia P

Abstract

PMID: 30129523 [PubMed - indexed for MEDLINE]

Angiosarcoma associated with hypertrichosis.

Eur J Dermatol. 2018 Oct 01;28(5):677-678

Authors: Shibata Y, Matsumoto Y, Shiga T, Nakajima H, Nakajima K, Sano S

Abstract

PMID: 29941407 [PubMed - indexed for MEDLINE]

Chronic Otitis Media Associated with Cholesteatoma in a Case of the Say-Barber-Biesecker-Young-Simpson Variant of Ohdo Syndrome.

Am J Case Rep. 2019 Feb 10;20:175-178

Authors: Galletti B, Gazia F, Freni F, Nicita RA, Bruno R, Galletti F

Abstract
BACKGROUND The Say-Barber-Biesecker-Young-Simpson (SBBYS) variant of Ohdo syndrome is characterized by congenital hypothyroidism, facial dysmorphism, postaxial polydactyly, and mental retardation. The SBBYS variant of Ohdo syndrome is extremely rare with only 19 cases previously reported in the literature. A case is presented of chronic otitis media associated with cholesteatoma in a six-year-old boy with the SBBYS variant of Ohdo syndrome. CASE REPORT A 6-year-old boy presented with perforation of the tympanic membrane and a cholesteatoma in the mesotympanic-attic region associated with chronic otitis media. The child had previously been diagnosed with the SBBYS variant of Ohdo syndrome. Following computed tomography (CT) and magnetic resonance imaging (MRI), tympanoplasty was performed with removal of the lesion. CONCLUSIONS This is the first case described in the literature of chronic otitis media associated with cholesteatoma in a patient with the SBBYS variant of Ohdo syndrome. This case demonstrates the importance of specialist otolaryngology referral for patient management.

PMID: 30739122 [PubMed - indexed for MEDLINE]