A novel fibroblast growth factor receptor 2 mutation in Crouzon syndrome associated with Chiari Type I malformation and syringomyelia

2002 ◽  
Vol 97 (2) ◽  
pp. 396-400 ◽  
Author(s):  
Hironori Fujisawa ◽  
Mitsuhiro Hasegawa ◽  
Shinya Kida ◽  
Junkoh Yamashita
Keyword(s):  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Type I ◽  
Crouzon Syndrome ◽  
Content Type ◽  
Chiari Type I Malformation ◽  
Lambdoid Synostosis ◽  
Chiari I ◽  
Chiari Type I ◽  
Fine Print

Object. It has been reported that due to premature synostosis of the lambdoid suture in the first 24 months of life, more than 70% of patients with Crouzon syndrome concurrently suffer from chronic tonsillar herniation (Chiari Type I malformation) and some (20%) associated syringomyelia. The goal of the present study was to examine mutations in the fibroblast growth factor receptor (FGFR) genes in Crouzon syndrome and its related conditions. Methods. Five patients were studied: three with Crouzon syndrome (one sporadic and two familial), one with sporadic Chiari I with syringomyelia, and one with unilateral lambdoid synostosis. Deoxyribonucleic acid was screened for FGFR1–3 mutations by using single-strand conformational polymorphism and subsequent direct sequencing. Two types of missense mutations were detected in the FGFR2 gene, Cys342Trp (1205, TGC → TGG) in a patient with sporadic Crouzon syndrome and Tyr281Cys (1021, TAC → TGC) in two siblings (brother and sister) with familial Crouzon syndrome, respectively. The former has been reported only in sporadic cases but the latter has not previously been identified. A polymorphism in the FGFR3 gene, Asn294Asn (882, AAT → AAC), was also detected in three patients. No mutation was found in the patient with sporadic Chiari I with syringomyelia. Conclusions. The FGFR2 missense mutation was detected in Crouzon syndrome but not in sporadic Chiari I with syringomyelia or lambdoid synostosis. A novel FGFR2 mutation, Tyr281Cys, was found in familial Crouzon syndrome with Chiari I and syringomyelia. It may be informative to look for this in patients with Crouzon syndrome and associated syringomyelia.

Spontaneous drainage of syringomyelia

1993 ◽  
Vol 79 (1) ◽  
pp. 132-134 ◽  
Author(s):  
Antonio Santoro ◽  
Roberto Delfini ◽  
Gualtiero Innocenzi ◽  
Claudio Di Biasi ◽  
Guido Trasimeni ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Mr Imaging ◽  
Clinical Course ◽  
Spontaneous Resolution ◽  
Type I ◽  
Content Type ◽  
Chiari Type I Malformation ◽  
Spinal Subarachnoid Space ◽  
Chiari Type I ◽  
Fine Print

✓ Two cases are reported of Arnold-Chiari type I malformation associated with syringomyelia, in which magnetic resonance (MR) imaging revealed spontaneous decompression of the syrinx. In one case axial MR imaging sections showed a communication between the syrinx and the spinal subarachnoid space, which supports the hypothesis that fissuring of the cord parenchyma is instrumental in the spontaneous resolution of syringomyelia. The MR imaging changes were not accompanied by variations in the patients' clinical course.

Chiari Type I malformation and syringomyelia in unrelated patients with blepharophimosis

1998 ◽  
Vol 89 (5) ◽  
pp. 835-838 ◽  
Author(s):  
Philippe Paquis ◽  
Michel Lonjon ◽  
Madeleine Brunet ◽  
Jean Claude Lambert ◽  
Patrick Grellier
Keyword(s):  
Autosomal Dominant ◽  
Radicular Pain ◽  
Hereditary Diseases ◽  
Type I ◽  
Content Type ◽  
Chiari Type ◽  
Chiari Type I Malformation ◽  
Familial Type ◽  
Chiari Type I ◽  
Fine Print

✓ Syringomyelia is a rare, mainly sporadic disease of the spinal cord, which is associated with 80% of cases in which a Chiari Type I malformation is also present. A mendelian transmission of syringomyelia (autosomal dominant or recessive) has been proposed in approximately 2% of reported cases. The association of syringomyelia with hereditary diseases (Noonan's syndrome, phacomatoses) has been mentioned frequently in the literature. The authors report the presence of a Chiari Type I malformation accompanied by syringomyelia in two unrelated patients affected by a familial Type II blepharophimosis—ptosis—epicanthus inversus syndrome (BPES). The first patient was a 35-year-old woman who presented with a right C-8 root paresia. The second case involved a 20-year-old man who complained of cervical radicular pain. Both belong to families in which BPES was segregated in an autosomal dominant modality, but other family members had no known neurological symptoms. To the authors' knowledge, such a combination has never been described. Perhaps the possible involvement of a genetic component in some cases of Chiari Type I—associated syringomyelia will someday be debated.

Hindbrain herniation: an unusual occurrence after shunting an intracranial arachnoid cyst

1994 ◽  
Vol 81 (1) ◽  
pp. 126-129 ◽  
Author(s):  
Maher I. Hassounah ◽  
Bengt E. Rahm
Keyword(s):  
Arachnoid Cyst ◽  
Type I ◽  
Content Type ◽  
Stereotactic Aspiration ◽  
Chiari Type I Malformation ◽  
Hindbrain Herniation ◽  
Intracranial Arachnoid Cyst ◽  
Unusual Occurrence ◽  
Chiari Type I ◽  
Fine Print

✓ The case is presented of a prepontine arachnoid cyst in a 28-year-old woman. She was treated by craniotomy, stereotactic aspiration, internal shunting, and finally by insertion of a cystoperitoneal shunt. Eight months later she developed an asymptomatic Arnold-Chiari type I malformation. The pathogenesis of this unusual hindbrain herniation is explained on the basis of the differential pressure between two compartments and cephalocranial disproportion.

Syringomyelia extending to the basal ganglia

1989 ◽  
Vol 71 (4) ◽  
pp. 616-617 ◽  
Author(s):  
Satoshi Okada ◽  
Yoshio Nakagawa ◽  
Kimiyoshi Hirakawa
Keyword(s):  
Magnetic Resonance Imaging ◽  
Pyramidal Tract ◽  
Type I ◽  
Sensory Disturbance ◽  
Resonance Imaging ◽  
Content Type ◽  
Chiari Type I Malformation ◽  
The Right ◽  
Chiari Type I ◽  
Fine Print

✓ A 10-year-old girl was admitted to the hospital with complaints of progressive right hemiparesis and sensory disturbance. Magnetic resonance imaging revealed a Chiari Type I malformation and syringomyelia from T-10 to C-1. The syrinx extended from the medulla to the right putamen along the pyramidal tract.

Hydrocephalus due to idiopathic stenosis of the foramina of Magendie and Luschka

2003 ◽  
Vol 98 (4) ◽  
pp. 897-902 ◽  
Author(s):  
Carine Karachi ◽  
Caroline Le Guérinel ◽  
Pierre Brugières ◽  
Eliane Melon ◽  
Philippe Decq
Keyword(s):  
Fourth Ventricle ◽  
Third Ventricle ◽  
Ventricular Volume ◽  
Transverse Diameter ◽  
Type I ◽  
Content Type ◽  
Chiari Type I Malformation ◽  
Chiari Type I ◽  
Fine Print ◽  
Foramen Of Luschka

✓ Idiopathic stenosis of the foramina of Magendie and Luschka is a rare cause of obstructive hydrocephalus involving the four ventricles. Like other causes of noncommunicating hydrocephalus, it can be treated with endoscopic third ventriculostomy (ETV). Three patients who were 21, 53, and 68 years of age presented with either headaches (isolated or associated with raised intracranial pressure) or vertigo, or a combination of gait disorders, sphincter disorders, and disorders of higher functions. In each case, magnetic resonance (MR) imaging demonstrated hydrocephalus involving the four ventricles (mean transverse diameter of third ventricle 14.15 mm; mean sagittal diameter of fourth ventricle 23.13 mm; and mean ventricular volume 123.92 ml) with no signs of a Chiari Type I malformation (normal posterior fossa dimensions, no herniation of cerebellar tonsils). The diagnosis of obstruction was confirmed using ventriculography (in two patients) and/or MR flow images (in two patients). All patients presented with marked dilation of the foramen of Luschka that herniated into the cisterna pontis. All patients were treated using ETV. No complications were observed. All three patients became asymptomatic during the weeks following the surgical procedure and remained stable at a mean follow-up interval of 36 months. Postoperative MR images demonstrated regression of the hydrocephalus (mean transverse diameter of third ventricle 7.01 mm; mean sagittal diameter of fourth ventricle 16.6 mm; and mean ventricular volume 79.95 ml), resolution of dilation of the foramen of Luschka, and good patency of the ventriculostomy (flow sequences). These results confirm the existence of hydrocephalus caused by idiopathic fourth ventricle outflow obstruction without an associated Chiari Type I malformation, and the efficacy of ETV for this rare indication.

Sleep Apnea and the Chiari I Malformation: Case Report

Neurosurgery ◽  
1988 ◽  
Vol 23 (4) ◽  
pp. 508-510 ◽  
Author(s):  
Philip Levitt ◽  
Martin A. Cohn
Keyword(s):  
Case Report ◽  
Sleep Apnea ◽  
Chiari I Malformation ◽  
Type I ◽  
Ambulatory Patient ◽  
Chiari Type ◽  
Chiari Type I Malformation ◽  
Chiari I ◽  
Chiari Type I

Abstract The authors report the case of an ambulatory patient who presented with sleep apnea episodes of the central and obstructive types and an associated Chiari Type I malformation. The central episodes stopped and the obstructive episodes decreased markedly after decompression. The improvement in the so-called obstructive episodes was unexpected and indicates that they may have been on a central basis.

Negative autoregulation of fibroblast growth factor receptor 2 expression characterizing cranial development in cases of Apert (P253R mutation) and Pfeiffer (C278F mutation) syndromes and suggesting a basis for differences in their cranial phenotypes

2001 ◽  
Vol 95 (4) ◽  
pp. 660-673 ◽  
Author(s):  
Jonathan A. Britto ◽  
Rachel L. Moore ◽  
Robert D. Evans ◽  
Richard D. Hayward ◽  
Barry M. Jones
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Apert Syndrome ◽  
Fibroblast Growth ◽  
Content Type ◽  
Pfeiffer Syndrome ◽  
Negative Autoregulation ◽  
Fine Print

Object. Heterogeneous mutations in the fibroblast growth factor receptor 2 gene (FGFR2) cause a range of craniosynostosis syndromes. The specificity of the Apert syndrome—affected cranial phenotype reflects its narrow mutational range: 98% of cases of Apert syndrome result from an Ser252Trp or Pro253Arg mutation in the immunoglobulin-like (Ig)IIIa extracellular subdomain of FGFR2. In contrast, a broad range of mutations throughout the extracellular domain of FGFR2 causes the overlapping cranial phenotypes of Pfeiffer and Crouzon syndromes and related craniofacial dysostoses. Methods. In this paper the expression of FGFR1, the IgIIIa/c and IgIIIa/b isoforms of FGFR2, and FGFR3 is investigated in Apert syndrome (P253R mutation)— and Pfeiffer syndrome (C278F mutation)—affected fetal cranial tissue and is contrasted with healthy human control tissues. Both FGFR1 and FGFR3 are normally expressed in the differentiated osteoblasts of the periosteum and osteoid, in domains overlapped by that of FGFR2, which widely include preosseous cranial mesenchyme. Expression of FGFR2, however, is restricted to domains of advanced osseous differentiation in both Apert syndrome— and Pfeiffer syndrome—affected cranial skeletogenesis in the presence of fibroblast growth factor (FGF)2, but not in the presence of FGF4 or FGF7. Whereas expression of the FGFR2-IgIIIa/b (KGFR) isoform is restricted in normal human cranial osteogenesis, there is preliminary evidence that KGFR is ectopically expressed in Pfeiffer syndrome—affected cranial osteogenesis. Conclusions. Contraction of the FGFR2-IgIIIa/c (BEK) expression domain in cases of Apert syndrome— and Pfeiffer syndrome—affected fetal cranial ossification suggests that the mutant activation of this receptor, by ligand-dependent or ligand-independent means, results in negative autoregulation. This phenomenon, resulting from different mechanisms in the two syndromes, offers a model by which to explain differences in their cranial phenotypes.

Clinical variability in patients with Apert's syndrome

1999 ◽  
Vol 90 (3) ◽  
pp. 443-447 ◽  
Author(s):  
Elisabeth Lajeunie ◽  
Rhoda Cameron ◽  
Vincent El Ghouzzi ◽  
Nathalie de Parseval ◽  
Pierre Journeau ◽  
...  
Keyword(s):  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Rare Mutation ◽  
Content Type ◽  
Clinical Variability ◽  
Apert's Syndrome ◽  
Double Base ◽  
Adjacent Amino Acid ◽  
Difficult Cases ◽  
Fine Print

Object. Apert's syndrome is characterized by faciocraniosynostosis and severe bony and cutaneous syndactyly of all four limbs. The molecular basis for this syndrome appears remarkably specific: two adjacent amino acid substitutions (either S252W or P253R) occurring in the linking region between the second and third immunoglobulin domains of the fibroblast growth factor receptor (FGFR)2 gene. The goal of this study was to examine the phenotype/genotype correlations in patients with Apert's syndrome.Methods. In the present study, 36 patients with Apert's syndrome were screened for genetic mutations. Mutations were detected in all cases. In one of the patients there was a rare mutation consisting of a double—base pair substitution in the same codon (S252F). A phenotypical survey of our cases was performed and showed the clinical variability of this syndrome. In two patients there was no clinical or radiological evidence of craniosynostosis. In two other patients with atypical forms of syndactyly and cranial abnormalities, the detection of a specific mutation was helpful in making the diagnosis.Conclusions. The P253R mutation appears to be associated with the more severe forms, with regard to the forms of syndactyly and to mental outcome. The fact that mutations found in patients with Apert's syndrome are usually confined to a specific region of the FGFR2 exon IIIa may be useful in making the diagnosis and allowing genetic counseling in difficult cases.

scholarly journals Outcome of Posterior Fossa Decompression for Chiari Type I Malformation with Syringomyelia

2019 ◽  
Vol 16 (1) ◽  
pp. 35-38
Author(s):  
Sagar Koirala ◽  
Suresh Bishokarma ◽  
Dinesh Nath Gongal ◽  
Henry Thomas Marsh
Keyword(s):  
Posterior Fossa ◽  
Chiari I Malformation ◽  
Posterior Fossa Decompression ◽  
Type I ◽  
Chiari Type ◽  
Chiari Type I Malformation ◽  
Tertiary Center ◽  
Clinical And Radiological Outcome ◽  
Chiari I ◽  
Chiari Type I

There are various treatment approaches for treating Chiari type I malformation with syringomyelia. Despite various choices, consensus for one particular approach is lacking. The objective of this study is to find out the clinical and radiological outcome of standard posterior fossa decompression incorporating removal of C1 arch with lax duroplasty in such cases. A retrospective study based on data acquired from a single tertiary center were analyzed. All cases who underwent posterior fossa decompression incorporating removal of C1 arch with lax duroplasty over a period of five years were included and their clinical and radiological progress were recorded during OPD follow up at 6 months. Out of 21 cases, occipital headache with nape of neck pain was the predominant complaint accounting to 71% followed by sensory symptoms and motor weakness, 61% and 33% respectively. Pain resolved in 93%, weakness in 71% and sensory symptoms in 69% of the cases. Only one patient developed hydrocephalus requiring shunting. Radiological improvement of syringomyelia were documented in 76.1% of the patients. There was no mortality. Posterior fossa decompression incorporating removal of C1 arch and lax duroplasty is a safe approach with good outcome in patients with Chiari I malformation with syringomyelia.

Fibroblast growth factor receptor 3 mutation in nonsyndromic coronal synostosis: clinical spectrum, prevalence, and surgical outcome

2000 ◽  
Vol 92 (4) ◽  
pp. 631-636 ◽  
Author(s):  
Dominique Renier ◽  
Vincent El Ghouzzi ◽  
Jacky Bonaventure ◽  
Martine Le Merrer ◽  
Elizabeth Lajeunie
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Dna Analysis ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Fibroblast Growth ◽  
Recurrent Point ◽  
Content Type ◽  
Coronal Synostosis ◽  
Fine Print

Object. A recurrent point mutation in the fibroblast growth factor receptor 3 gene that converts proline 250 into arginine has been reported recently in cases of apparently nonsyndromic coronal craniosynostosis. The goal of the present study was to examine the phenotype of patients in whom this mutation was present, to determine the prevalence of the condition, and to assess the functional and the morphological outcome of the surgically treated patients.Methods. A DNA analysis was performed in 103 children suffering from apparently isolated coronal synostosis, 41 of whom had bilateral and 62 of whom had unilateral disease. There were 31 boys and 72 girls in the study group. Sixty cases were sporadic and 43 were familial; the 43 familial cases arose in 33 unrelated families. The mutation was found in seven (12%) of 60 sporadic cases and in 24 (73%) of the 33 families. The functional and morphological results were assessed in all surgically treated patients who had at least 1 year of follow up and who were at least 3 years of age at the time of assessment. A comparison was made between patients with the mutation and those without.Conclusions. The most typical presentation was seen in girls and consisted of a bicoronal synostosis resulting in a severe brachycephaly associated with mild hypertelorism and marked bulging of the temporal fossae, which resulted in a huge enlargement of the upper part of the face. The most frequently associated extracranial anomaly was brachydactyly, identified either clinically or radiologically. Based on the proportion of bilateral and unilateral coronal synostoses, the present data indicate that the mutation is associated with more severe cases and that girls with the mutation are more severely affected than boys. The functional and morphological results were worse in patients in whom the mutation was present as compared with those in whom it was not.

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