软骨发育不全,囟门早闭

CASE REPORTSUnilateral Frontosphenoidal Craniosynostosis With Achondroplasia: A Case ReportBradley A.Hubbard,M.D.,Jerome L.Gorski,M.D.,Arshad R.Muzaffar,M.D.,F.A.C.S.Isolated,premature fusion of the frontosphenoidal suture is rare.This reportdescribes an unusual combination of frontosphenoidal craniosynostosis andachondroplasia.Although craniosynostosis is known to occur in allelicconditions such as thanatophoric dysplasia,craniosynostosis in individualswith achondroplasia is exceedingly rare.Due to the distracting diagnosis ofachondroplasia or inadequate knowledge of craniosynostosis,the abnormalhead shape was initially treated by other physicians with helmet molding.Plasticsurgery consultation was obtained at2years of age and surgical care wasprovided.An acceptable head shape was obtained,but the delay in appropriateevaluation was disconcerting.To our knowledge this is the first reported case ofisolated frontosphenoidal craniosynostosis associated with achondroplasia.KEY WORDS:achondroplasia,craniosynostosis,frontosphenoidalCases of frontal plagiocephaly can be categorized as either deformational or synostotic(Bruneteau and Mulli-ken,1992).Deformational frontal plagiocephaly is thought to be caused by intrauterine compression of the fetal cranium,intrauterine restriction of cranial growth,or postnatal positioning,the latter being increasingly rare due to the American Academy of Pediatrics’Back to Sleep Campaign(Argenta et al.,1996;Turk et al.,1996).Molding helmet therapy is rarely needed and surgical treatment is nearly contraindicated because spontaneous improvement is the rule(Hansen and Mulliken,1994).Unilateral synostotic frontal plagiocephaly due to fronto-parietal(coronal)suture premature closure is uncommon, estimated at1in10,000live births(Bruneteau and Mulliken, 1992).Most cases are sporadic and nonsyndromic,although it has been described in Saethre-Chotzen syndrome,cranio-frontonasal syndrome,and Muenke syndrome(FGFR3 Pro250Arg mutation)(Muenke et al.,1997;Orr et al.,1997; Gripp et al.,1998).Synostotic frontal plagiocephaly almost uniformly requires operative intervention.In unilateral coronal synostosis,the frontoparietal suture is always fused and may occasionally involve the lateral portion of the frontosphenoidal suture(Gripp et al.,1998).However,the medial frontosphenoidal suture and sphe-noethmoidal synchondrosis are not fused in unilateral coronal synostosis(Rogers et al.,2002).This is unlike the bilateral coronal synostosis,as found in Apert,Crouzon, and Pfeiffer syndromes,where there is complete fusion of the basal coronal ring.These syndromes,in addition to Beare-Stevenson cutis gyrata syndrome and Jackson-Weiss syndrome,have been linked to dominant mutations in the FGFR1and FGFR2genes(Vajo et al.,2000). Achondroplasia,the most common form of short-limbed dwarfism in humans,occurs in1in15,000to1in40,000 live births.More than90%of cases are sporadic and are associated with advanced paternal age.More than97%of persons with achondroplasia have a Gly380Arg mutation in the FGFR3gene.To date there have been12reported cases of unilateral synostosis of the basal coronal ring without frontoparietal synostosis(Currarino,1985;Francel et al.,1995;Rogers et al.,2002;de Ribaupierre et al.,2008;Marucci et al.,2009). Two of these were of the frontozygomatic suture(Currar-ino,1985),the rest being of the frontosphenoidal suture. There has been one reported case of craniosynostosis in combination with achondroplasia.The Gly380Arg FGFR3 achondroplasia gene was detected in combination with a multiple suture synostosis and phenotypic cloverleaf deformity(Karadimas et al.,2006).In this case report we detail the clinical,radiological,and genetic history of what is,to our knowledge,the first reported patient with unilateral frontosphenoidal synostosis and achondroplasia.C ASE R EPORTA full-term boy was born via an uncomplicated vaginal delivery to a woman with an uncomplicated medical historyDr.Hubbard is Integrated Resident PGY-5,Department of Surgery, Division of Plastic Surgery,and Dr.Gorski is Professor,Department of Child Health,Division of Genetics,University of Missouri,Columbia, Missouri.Dr.Muzaffar is Associate Professor and Director–Craniofacialand Pediatric Plastic Surgery,Department of Surgery,Division of Plastic Surgery,University of Missouri,Columbia,Missouri.Submitted January2010;Accepted August2010.Address correspondence to:Dr.Arshad R.Muzaffar,University of Missouri,Department of Surgery,Division of Plastic Surgery,One Hospital Drive,Columbia,MO65212.DOI:10.1597/09-266631and a father who had a confirmed diagnosis of achondro-plasia.The father’s diagnosis was confirmed in childhood by medical genetics;he had clinical and radiographic features diagnostic for achondroplasia,including interpe-duncular narrowing of the lumbar vertebrae.His adult height was 142cm.The infant’s diagnosis of achondropla-sia was suspected prenatally by ultrasound.Clinical evaluations and radiographic studies confirmed the infant’s suspected diagnosis.Within weeks of birth,the infant was noted to have left frontal plagiocephaly.Initially,the patient’s pediatrician and geneticist thought the infant had a mild left frontal deformational plagio-cephaly.No evidence of torticollis was noted.At 6months of age,helmet therapy was begun because improvement had not been noted.This was continued for nearly 10months without improvement.Developmentally,the patient was noted to be achieving normal milestones.At the age of 2,the patient was referred for evaluation by a craniofacial surgeon (A.R.M.)regarding his head shape (Fig.1,right column).He had significant flattening of the left lateral forehead and supraorbital region with right-sided frontal bossing.A furrow or crease ran obliquely in the left frontotemporal region from anterior-inferior to superior-posterior,accentuating the significant bulge of the ipsilateral parietal bone.The vertical dimension of the left orbit was compressed,although there was no exorbitism.The midface was symmetric,but the nasal root deviated to the right.The ear position was grossly symmetric (Fig.2).Due to concern for underlying synostosis,a computer-ized tomography (CT)scan of the head was performed with three dimensional (3D)reformatting (Fig.3,left column).The scan demonstrated left frontal flatness with severe forehead and supraorbital rim retrusion and inferior displacement.The anterior-posterior distance in the orbit was foreshortened,thus making the greater sphenoid wing appear more anteriorly displaced and transversely oriented.The left frontal skull was volume deficient and mild ventriculomegaly was noted.The cranial base had a 15u angulation to the right,using Lo’s measurement (Lo et al.,1996)(Fig.4).The left frontosphenoidal suture was fused,as was the metopic suture.The coronal ring sutures were otherwise patent,and the sagittal suture was patent and midline.Due to the patient’s significant craniofacial deformity as well as evident pressure-related changes to the left frontal temporal region of the skull,the parents consented to fronto-orbital correction.The patient underwent frontal orbital advancement and anterior cranial vaultremodelingFIGURE 1Side-by-side comparison of preoperative and 1year postoperative from second surgery photographs.a:Preoperative anterior view.b:1year post-op from second surgery,anterior view.c:Preoperative left lateral view (middle).d:1year post-op from second surgery,left lateral view (middle).e:Preoperative vertex view (bottom).f:1year post-op from second surgery,vertex view (bottom).632Cleft Palate–Craniofacial Journal,September 2011,Vol.48No.5at the age of 2K years.The operative procedure involved remodeling and advancement of the fronto-orbital ban-deau,frontal bone remodeling,parietal/temporal bone barrel-staving,and bilateral lateral canthoplasties.The patient fared well immediately following surgery.At the age of 3K years,the patient underwent a repeat fronto-orbital correction due to asymmetry.This procedure included left-sided bandeau readvancement,left frontal/temporal bone remodeling,and left canthoplasty.The patient recovered well from surgery.Postoperative assess-ment 1year following the second procedure revealed marked improvement in head shape and symmetry.Postoperative photographs (Fig.1,right column)and 3D CT scan (Fig.2,right column)were obtained at this time.D ISCUSSIONTen cases of frontosphenoidal craniosynostosis have been reported in the literature (Francel et al.,1995;Rogers et al.,2002;Karadimas et al.,2006;de Ribaupierre et al.,2007;Marucci et al.,2009).Although no true incidence is known,it is an exceedingly rare subtype of unilateral coronal ring synostosis.Dominant genetic mutations causing synostotic plagiocephaly are generally found in the FGFR1and FGFR2genes (i.e.,Pfeiffer syndrome,Crouzon syndrome,Apert syndrome,Beare-Stevenson cutis gyrata syndrome,and Jackson-Weiss syndrome).The FGFR1and FGFR2mutations are thus predomi-nantly associated with disorders of membranous bone growth.Alternatively,disorders of endochondral bone growth have been associated with FGFR3,including achondroplasia,hypochondroplasia,and thanatophoric dysplasia (Vajo et al.,2000).More recently,Muenke craniosynostosis and Crouzon syndrome with acanthosisnigricans have been linked to the FGFR3gene (Muenke et al.,1997).This case brings forward two important points:Differ-entiation of frontal plagiocephaly and unilateral coronal craniosynostosis can be difficult to distinguish with the untrained eye,and achondroplasia can be associated with membranous bone-growth disorders.When evaluating patients we must be ever cognizant of Hickam’s dictum,‘‘Patients can have as many diseases (diagnoses)as they well please.’’The spectrum of phenotypic changes with anterior plagiocephaly is relatively broad and can be confusing.However,there are clear differences that allow accurate diagnosis,usually without the need for radiographs (Hansen and Mulliken,1994).Deformational frontal plagiocephaly is characterized by the ‘‘parallelogrammic head.’’Specifically,there is ipsilateral frontal and malar flattening,inferior and posterior displacement of the ipsilateral ear,and narrowed palpebral fissure and eye-brow.The chin may deviate toward the involved side,but the nasal root is midline.There also may be bossing of the ipsilateral and flattening of the contralateral occiput.Conversely,unilateral coronal synostosis is characterized by ipsilateral ear and malar eminence anterior displace-ment.The palpebral fissure is vertically elongated;the supraorbital rim and eyebrow are displaced superiorly and posteriorly.The nasal root is deviated toward the flattened side,and the chin often points to the contralateral side.These differences have been well described previously by Hansen and Mulliken (1994).The phenotypic changes associated with isolated fusion of the frontosphenoidal suture have been variably de-scribed in the literature.An excellent review of these differences was written by Rogers et al.(2002).The craniofacial appearance is similar to that of unilateral coronal synostosis except the maxilla is symmetric or slightly retruded,the nasal root is midline or contralaterally deviated,the chin and sagittal suture are midline,and the ipsilateral ear is symmetric or slightly posterior.The variability of presentation may correlate with the severity,which is rated by the magnitude of cranial base angulation (Rogers et al.,2002).Achondroplasia is characterized by deficient endochon-dral bone growth.Because the majority of the cranial base is preformed in cartilage,one would expect multiple craniofacial skeletal growth deficiencies.These expected changes are blunted by the numerous growth centers,also seen in the vertebral column leading to normal trunk length.Additionally,the force of the expanding brain is greater than normal in these children due to communicat-ing hydrocephalus commonly resulting in enlarged calvaria and frontal bossing.It would therefore be extremely uncommon to have anterior deformational plagiocephaly in spite of the opposing force from the enlarged frontal lobes.Furthermore,one could argue that achondroplastic children would therefore have less tolerance tocraniosyn-FIGURE 2Preoperative axial CT scan image demonstrating nearly symmetric ear placement.Hubbard et al.,UNILATERAL FRONTOSPHENOIDAL CRANIOSYNOSTOSIS WITH ACHONDROPLASIA 633ostosis and should be more urgently decompressed,due to the greater expansion rate of the underlying brain.Concerning the other craniofacial characteristics in achondroplasia,an excellent morphometric analysis was reported by Cohen et al.(1985).In short,achondroplastic children can be characterized by enlarged calvaria,frontal bossing,large frontal sinuses,occipital prominence,normal anterior cranial base length,strikingly shortened posterior cranial base length,an acute cranial base angle,a short nasal bone that was deformed and depressed,short upper facial height,recessed maxilla,posterior tilt of the nasal floor,and a prognathic mandible.C ONCLUSIONTo our knowledge,this case represents the first report of isolated frontosphenoidal craniosynostosis in a patient with achondroplasia.Differentiation of anterior deformational plagiocephaly and unilateral coronal ring craniosynostosis can be difficult to distinguish for the untrained observer.However,there are clear differences that allow accurate diagnosis.In combination with achondroplasia,one should be especially wary of craniosynostosis due to the extra demands on the membranous bone growth resulting from increased brain volume and lack of endochondralboneFIGURE 3Side-by-side comparison of 3D CT scan reconstructions performed preoperatively and 1year postoperative from second surgery.a:Preoperative anterior-posterior view.b:1year post-op from second surgery,anterior-posterior view.c:Preoperative left lateral view.d:1year post-op from second surgery,left lateral view.e:Preoperative vertex view.f:1year post-op from second surgery,vertex view.g:Preoperative basilar view.h:1year post-op from second surgery,basilar view.634Cleft Palate–Craniofacial Journal,September 2011,Vol.48No.5growth at the skull base.Early referral and radiologic examination,if necessary,should be the rule in this rare circumstance.R EFERENCESArgenta LC,David LR,Wilson JA,Bell WO.An 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