Showing papers on "Neurocristopathy published in 2005"

Pigment cell-related manifestations in neurofibromatosis type 1: an overview.

Abstract: Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous disorder, affecting approximately 1 in 3500 individuals. The most commonly seen tumors in NF1 patients are the (sub)cutaneous neurofibromas. However, individuals with NF1 typically present in childhood with well-defined pigmentary defects, including cafe-au-lait macules (CALMs), intertriginous freckling and iris Lisch nodules. NF1 is considered a neurocristopathy, primarily affecting tissues derived from the neural crest. Since the pigment producing melanocyte originates in the neural crest, the presence of (hyper)pigmentary lesions in the NF1 phenotype because of changes in melanocyte cell growth and differentiation is to be expected. We want to discuss the pigmentary cutaneous manifestations of NF1 represented by CALMs and intertriginous freckles and the pigmentary non-cutaneous manifestations represented by iris Lisch nodules. Several hypotheses have been suggested in explaining the poorly understood etiopathogenesis of CALMs. Whether other pigmentary manifestations might share similar etiopathogenic mechanisms remains obscure. Additional attention will be drawn to a readily seen phenomenon in NF1: hyperpigmentation overlying (plexiform) neurofibromas, which could suggest common etiopathogenetic-environmental cues or mechanisms underlying CALMs and neurofibromas. Finally, we want to address the relationship between malignant melanoma and NF1.

Invited Comment Updated Diagnostic Criteria for CHARGE Syndrome: A Proposal

Abstract: Alain Verloes*Clinical Genetics Unit, Hoˆpital Robert Debre´, Paris, France‘‘CHARGE association’’ is a well-known entity of unknownorigin. It was originally delineated by Bryan Hall [1979] in17 children with multiple congenital anomalies (MCA) includ-ingchoanal atresiaand,independently by Hittneretal.[1979]in 10 MCA patients with coloboma, hence the eponymic Hall–Hittner syndrome which is sometimes used for it Graham,2001. Pagon et al. [1981] coined ‘‘CHARGE,’’ an acronym sum-marizing the five cardinal clinical features: ocular Coloboma,Heart defects of any type, Atresia of the choanae, Retardation(ofgrowthand/orofdevelopment), Genitalanomalies,andEaranomalies (abnormal pinnae or hearing loss). Classically, tomake a diagnosis of CHARGE complex, 4/7 signs need to bepresent [Oley et al., 1988], and one should be either choanalatresiaoracoloboma[Pagonetal.,1981].Manyotherdevelop-mental anomalies have been reported in CHARGE beyond theacronymic components [Pagon et al., 1981; Oley et al., 1988;Blake et al., 1998; Tellier et al., 1998; Gorlin et al., 2001].Amongthose,oticmalformations,anomaliesofthecranialandCNS midline structures, hypophyseal disorders, and brain-stem dysfunctions have to be stressed as emerging problemshidden beyond the historical cardinal features.Terminological Difficulty: Charge is notan Association, but a SyndromeAn association is the nonrandom cluster of developmentalanomalies that results from early teratogenic events thatoverlap in time and space. Whereas the term association isappropriate for VATER, which is a generalized blastogenicdefect, CHARGE is characterized by very specific develop-mentalanomaliesoftheopticvesicle,oticcapsule,midlineCNSstructures,andupperpharynx.CHARGEissupposedtoresultfrom abnormal differentiation of cephalic mesoderm andectoderm (otic placode and 1st branchial cleft), abnormalsetting (differentiation, migration, survival) of neural crestcells, abnormal interaction of neural crests (forming e.a. 1stand 2nd arch) with the cephalic mesoderm and the developingforebrain, and concomitant disorder in the development ofthe rhombencephalon out of which the neural crest cells havemigrated. CHARGE is thus a complex neurocristopathy, thetiming of which extends from blastogenesis (3rd week) to afterthe9thweekofgestation[Siebertetal.,1985;KirbyandWaldo,1990;Linetal.,1990].Eventhoughthecauseisnotknown,theterm ‘‘CHARGE syndrome’’ [Lubinsky, 1994; Amiel et al.,2001]isprobablymoreappropriate,andtheterm‘‘association’’should be dropped.Semicircular Canals in Charge Syndrome:An Underweighted and Overlooked Diagnostic ClueCochleovestibular abnormalities have recently been showntobeanimportantadditionaldysplasiainCHARGEsyndrome[Morgan et al., 1993; Murofushi et al., 1997; Dhooge et al.,1998; Amiel et al., 2001] In CHARGE, semicircular canals canbe aplastic and vestibular functions may be severely reduced.Cranial imaging frequently reveals absence or abnormality ofthe semicircular canals and, less frequently, hypoplasia of theupper turn of the cochlea or, in more severe cases, Mondinianomaly. In middle ear, hypoplastic long process of the incus,abnormal/absent oval window, and absence of stapediusmuscle are described. Facial nerve may show aberrant coursein the temporal bone, sometimes related with facial palsy.From an embryological point of view, inner ear develops fromthe ectodermally-derived otic placode, whereas middle andouter ear develop between the 5th and the 9th week from theectodermally-derived 1st branchial cleft and from the mesen-chyme (of neural crest origin) of the 1st and 2nd arches.Anatomical anomalies of middle and inner ear were notdirectly considered at the time where CHARGE was coined,probably because technical limits of medical imaging did notallow evaluation of these signs. Anomalies of the semicircularcanals are present in more than 80% of scanned CHARGEchildren [Morgan et al., 1993]. In another recent review ofcongenitalaplasiaofsemi-circularcanalswith‘‘relativelywell-formed cochlea’’ retrospectively selected in a population ofchildren candidate for inner ear implant electrode, Satar et al.[2003] presented a series of 15 patients. Ten of them werediagnosed as CHARGE syndrome. Among those, 85% of thecochleas were mildly or moderately dysplastic. Combined,those two series illustrate the high frequency and the highspecificity of canalar anomalies in CHARGE, a point furtherstressed in a recent review [Stjernholm, 2003]. Although theimportance of inner ear anomalies has been stressed, thepracticalconclusionshavenotbeencompletelydrawnintermsof diagnostic rules and syndrome definition.Variability of Expression in Charge:No Rules for an Old ProblemCHARGEwascoined22yearsagoandhasbeenshowntobeasuccessful acronym giving a simple rule of the thumb formaking or rejecting a diagnosis. Nevertheless, any dysmor-phologist knows how often he/she is led to the diagnosis of‘‘partial’’ or ‘‘atypical’’ CHARGE in patients who, usually,presents only with choanal atresia and some other signs.Curiously, this point has never been adequately discussed in*Correspondence to: Alain Verloes, Clinical Genetics Unit,Hoˆpital Robert Debre´, Paris, France.E-mail: alain.verloes@rdb.ap-hop-paris.frReceived 9 April 2004; Accepted 2 June 2004DOI 10.1002/ajmg.a.30559 2005 Wiley-Liss, Inc.

Fryns syndrome with Hirschsprung disease: support for possible neural crest involvement.

Abstract: Fryns syndrome is an autosomal recessive multiple congenital anomaly/mental retardation syndrome characterized by coarse face, distal limb hypoplasia, and diaphragmatic anomalies We describe a newborn girl with Fryns syndrome and Hirschsprung disease, an association that has been reported in five previous cases These patients support the hypothesis that the neural crest plays a role in the pathogenesis of Fryns syndrome Clinically asymptomatic or subtle anomalies that are in the spectrum of neural crest maldevelopment should be sought in all patients with Fryns syndrome including stillbirths, neonatal deaths, as well as long-term survivors We suspect that the clinical observation about Hirschsprung disease and Fryns syndrome may provide insight into its molecular mechanisms and candidate genes

Iris hypoplasia and aorticopulmonary septal defect: a neurocristopathy.

Abstract: Background: Errors in neural crest development are responsible for a number of ocular disorders. In some cases, these ocular abnormalities may be associated with systemic disorders, some of which may be life threatening. Methods: We reviewed the medical record of 3 children from 2 institutions with a similar constellation of ocular and cardiac abnormalities. Results: All 3 children had iris hypoplasia with pupils 6–7 mm in diameter that had minimal or no response to light or pharmacological agents. The ocular examinations were otherwise normal. All 3 children also had large aorticopulmonary septal defects which were surgically repaired. Conclusions: We report an association between iris hypoplasia and aorticopulmonary septal defects. Like the iris stroma, the aorticopulmonary septum forms from neural crest cells during embryogenesis which divide the truncus arteriosus into the ascending aorta and pulmonary trunk. Children with iris hypoplasia should undergo an immediate cardiac evaluation. It is important that opthalmologists be aware of the association between these two disorders since an aorticopulmonary septal defect is a life-threatening disorder.