Pfeiffer Syndrome Research Articles

P14.06: Prenatal diagnosis of Pfeiffer syndrome type II: a case report

P14.06: Prenatal diagnosis of Pfeiffer syndrome type <scp>II</scp>: a case report

Clinical and genetic characteristics of craniosynostosis in Hungary

Craniosynostosis, the premature closure of cranial sutures, is a common craniofacial disorder with heterogeneous etiology and appearance. The purpose of this study was to investigate the clinical and molecular characteristics of craniosynostoses in Hungary, including the classification of patients and the genetic analysis of the syndromic forms. Between 2006 and 2012, 200 patients with craniosynostosis were studied. Classification was based on the suture(s) involved and the associated clinical features. In syndromic cases, genetic analyses, including mutational screening of the hotspot regions of the FGFR1, FGFR2, FGFR3, and TWIST1 genes, karyotyping and FISH study of TWIST1, were performed. The majority (88%) of all patients with craniosynostosis were nonsyndromic. The sagittal suture was most commonly involved, followed by the coronal, metopic, and lambdoid sutures. Male, twin gestation, and very low birth weight were risk factors for craniosynostosis. Syndromic craniosynostosis was detected in 24 patients. In 17 of these patients, Apert, Crouzon, Pfeiffer, Muenke, or Saethre-Chotzen syndromes were identified. In one patient, multiple-suture craniosynostosis was associated with achondroplasia. Clinical signs were not typical for any particular syndrome in six patients. Genetic abnormalities were detected in 18 syndromic patients and in 8 relatives. In addition to 10 different, known mutations in FGFR1,FGFR2 or FGFR3, one novel missense mutation, c.528C>G(p.Ser176Arg), was detected in the TWIST1 gene of a patient with Saethre-Chotzen syndrome. Our results indicate that detailed clinical assessment is of paramount importance in the classification of patients and allows indication of targeted molecular testing with the highest possible diagnostic yield.

A Delayed Finding of a Tracheal Cartilaginous Sleeve in a Patient with Pfeiffer Syndrome Type 2 and a Complex Airway History.

Persistent airway obstruction symptoms in a 2½-year-old boy with Pfeiffer syndrome were attributed to facial abnormalities, central and obstructive sleep apnea, and tracheomalacia from a vascular ring. These findings delayed the diagnosis of a tracheal cartilaginous sleeve. Life expectancy in tracheal cartilaginous sleeve is improved by tracheostomy. Tracheal cartilaginous sleeve should be considered and investigated through airway endoscopy in children with fibroblast growth factor receptor-related craniosynostosis syndromes.

Aberrant facial flushing following monobloc fronto-facial distraction.

Patients with syndromic forms of craniosynostosis may experience functional problems such as raised intracranial pressure, proptosis, obstructive sleep apnoea and failure to thrive. The monobloc fronto-facial advancement with osteogenic distraction is increasingly used to correct these functional problems in one procedure as well as improve appearance. The authors report the phenomenon of post operative aberrant facial flushing - an unusual and previously unreported complication of the procedure. The case notes of 80 consecutive patients undergoing fronto-facial advancement by distraction using the rigid external distraction device (RED) were reviewed for features of aberrant facial flushing. Four out of eighty individuals developed facial flushing after monobloc fronto-facial distraction using the rigid external distractor (RED) frame. All were female with Crouzon or Pfeiffer syndromes causing the severe functional problems for which they underwent the surgery. They were aged 6-8 years. Following removal of the frame, they developed intermittent but severe facial flushing. The flushing spontaneously settled in three patients after up to four years but persists in the other child seven years after her surgery. Aberrant facial flushing is a rare but significant complication of monobloc fronto-facial surgery. It occurred in 4 of our 80 (5%) patients. The skull base osteotomies essential for the procedure are made anterior to the pterygopalatine ganglion and it is our contention that damage from these was responsible for a neuropraxia of its efferent nerve branches. A review of the autonomic control of the facial vascular system suggests that the phenomenon is due to an unequal process of recovery that leaves the cutaneous vasodilating parasympathetic or beta-adrenergic innervation relatively unopposed - a situation that persists until with time a normal balance of autonomic input is achieved.

FGFR2 mutation in a patient without typical features of Pfeiffer syndrome – The emerging role of combined NGS and phenotype based strategies

Pfeiffer syndrome (MIM: #101600) is a rare autosomal dominant disorder classically characterized by limb and craniofacial anomalies. It is caused by heterozygous mutations in the fibroblast growth factor receptors types 1 and 2 (FGFR1 and FGFR2).We applied a next generation sequencing (NGS) panel approach comprising all 2877 genes currently known to be causative for one or more Mendelian diseases combined with the phenotype based computational tool PhenIX (Phenotypic Interpretation of eXomes).We report on a patient presenting with multiple anomalies of hands and feet including brachydactyly and symphalangism. No clinical diagnosis could be established based on the clinical findings and testing of several genes associated with brachydactyly and symphalangism failed to identify mutations. Via next generation sequencing (NGS) panel approach we then identified a novel de novo missense FGFR2 mutation affecting an amino acid reported to be mutated in Pfeiffer syndrome. Since our patient shows typical radiological findings of Pfeiffer syndrome in hands and feet but at the same time lacks several characteristic features such as clinical signs of craniosynostosis and prominent eyes we suggest introducing the term “FGFR2 associated phenotypes” for similar cases.Our results highlight the emerging role of combined NGS and phenotype based bioinformatics strategies to establish clinical diagnoses.

Progressive postnatal pansynostosis: an insidious and pernicious form of craniosynostosis

OBJECT Progressive postnatal pansynostosis (PPP) is a rare form of craniosynostosis that is characterized by a normal head shape, insidious decrease in percentile head circumference, and high rates of elevated intracranial pressure (ICP). This investigation describes the clinical, radiographic, and genetic features of this entity. METHODS The authors' craniofacial database for the period 1997-2013 was retrospectively culled to identify patients who had a normal or near-normal head shape and CT-confirmed multiple-suture synostosis. Patients with kleeblatt-schädel or previous craniofacial surgery were excluded. All demographic information was collected and analyzed. RESULTS Seventeen patients fit the inclusion criteria. Nine patients had a syndromic diagnosis: Crouzon syndrome (n = 4), Pfeiffer syndrome (n = 2), Saethre-Chotzen syndrome (n = 1), Apert syndrome (n = 1), and achondroplasia (n = 1). With the exception of 3 patients with mild turricephaly, all patients had a relatively normal head shape. Patients were diagnosed at an average age of 62.9 months. Nearly all patients had some combination of clinical, radiographic, or ophthalmological evidence of increased ICP. CONCLUSIONS PPP is insidious; diagnosis is typically delayed because the clinical signs are subtle and appear gradually. All normocephalic infants or children with a known or suspected craniosynostotic disorder should be carefully monitored; any decrease in percentile head circumference or signs/symptoms of increased ICP should prompt CT evaluation.

Skull Base Morphology in Fibroblast Growth Factor Receptor Type 2-Related Faciocraniosynostosis

Children with faciocraniosynostosis present skull base abnormalities and may develop hydrocephalus or cerebellar tonsils ectopia (CTE). Several pathophysiological hypotheses were formulated in the past decades to explain these associations. However, no study has described in a genetically homogeneous population with confirmed fibroblast growth factor receptor type 2 (FGFR2) mutation eventual correlations between skull base abnormalities and hydrocephalus or CTE. To illustrate these features in children <2 years of age with a genetically confirmed FGFR2-related faciocraniosynostosis. We measured the foramen magnum area (FMA) and its sagittal and transversal components: the right, left, and mean area of the jugular foramen; the posterior fossa volume; and the cerebellar volume on preoperative millimetric computed tomography scan slices in 31 children with an FGFR2 mutation (14 with Crouzon syndrome, 11 with Apert syndrome, and 6 with Pfeiffer syndrome). They were compared with 17 children without synostosis. All children were <24 months of age. We correlated all these measures with the presence of hydrocephalus or CTE. We observed a significantly small FMA in children with Crouzon (P = .03) and in children with Pfeiffer (P = .05) resulting from a reduced sagittal diameter (P = .02 for Crouzon and P = .002 for Pfeiffer). Hydrocephalus was associated with small FMA (P = .02). The jugular foramen area, posterior fossa volume, and cerebellar volume were not associated with hydrocephalus or CTE. Hydrocephalus and CTE were statistically associated (P = .002). Hydrocephalus in FGFR2-related Crouzon and Pfeiffer syndromes is statistically associated with a small FMA. Hydrocephalus is statistically associated with CTE.

Morphology of the foramen magnum in syndromic and non-syndromic brachycephaly.

The shape and size of the foramen magnum (FM) can be altered in craniosynostoses. However, few studies have investigated these changes. In this paper, we investigate the morphology of the foramen magnum in syndromic and non-syndromic brachycephaly. Surface area, anteroposterior (AP) diameter, and transverse diameters of the FM were measured on high-resolution CT scans in children with Crouzon (25), Pfeiffer (21), Apert (26), Saethre-Chotzen (7) syndromes, and isolated bicoronal synostosis (9) and compared to an age-matched control group (30). A significantly smaller FM surface area was observed in Crouzon (6.3 ± 1.7cm(2)) and Pfeiffer (6.4 ± 2.3cm(2)) syndromes as compared to the control group (7.4 ± 1.3cm(2), p = 0.006 and p = .017, respectively). In comparison to the control group, no statistically significant alteration in FM surface area was noted in patients with Apert, Saethre-Chotzen, or isolated bicoronal synostosis (p = 0.37, p = 0.71, p = 0.40 respectively). The transverse diameter of FM was significantly smaller in Crouzon, Pfeiffer, and Apert syndromes compared to the control group (p = 0.005, p = 0.002, p = 0.03 respectively). In Saethre-Chotzen and isolated bicoronal synostosis, no difference in transverse diameter was demonstrated. Among all groups, only Crouzon syndrome showed reduced anteroposterior diameter as compared to controls (p = 0.005). In Pfeiffer and Apert syndromes, there was elongation of the shape of the FM with a relatively narrowed width as demonstrated in a significantly increased AP to transverse diameter ratio (p = 0.002 and p = 0.019, respectively). The FM shape and area is significantly altered in fibroblast growth factor receptor (FGFR)-related brachycephaly syndromes (Crouzon, Pfeiffer, and Apert), whereas in patients with Saethre-Chotzen syndrome (TWIST-1 mutation) and isolated non-syndromic bicoronal synostosis, the shape and mean FM area was not statistically different from that of normals. This study brings to light the important role of FGFRs on FM growth and shape. TWIST-1 mutation (Saethre-Chotzen syndrome) does not appear to have an important effect in shaping the FM.

Describing Crouzon and Pfeiffer syndrome based on principal component analysis

Crouzon and Pfeiffer syndrome are syndromic craniosynostosis caused by specific mutations in the FGFR genes. Patients share the characteristics of a tall, flattened forehead, exorbitism, hypertelorism, maxillary hypoplasia and mandibular prognathism. Geometric morphometrics allows the identification of the global shape changes within and between the normal and syndromic population. MethodsData from 27 Crouzon-Pfeiffer and 33 normal subjects were landmarked in order to compare both populations. With principal component analysis the variation within both groups was visualized and the vector of change was calculated. This model normalized a Crouzon-Pfeiffer skull and was compared to age-matched normative control data. ResultsPCA defined a vector that described the shape changes between both populations. Movies showed how the normal skull transformed into a Crouzon-Pfeiffer phenotype and vice versa. Comparing these results to established age-matched normal control data confirmed that our model could normalize a Crouzon-Pfeiffer skull. ConclusionsPCA was able to describe deformities associated with Crouzon-Pfeiffer syndrome and is a promising method to analyse variability in syndromic craniosynostosis. The virtual normalization of a Crouzon-Pfeiffer skull is useful to delineate the phenotypic changes required for correction, can help surgeons plan reconstructive surgery and is a potentially promising surgical outcome measure.

Respiratory and Cranial Complications during Anaesthesia in Pfeiffer Syndrome

Pfeiffer syndrome (PS) is rarely encountered, even at major craniofacial centers. Published reports indicate high mortality rates (25-85%) for severely affected subtypes. PS is characterized by bilateral coronal craniosynostosis, midface hypoplasia, beaked nasal tip, broad and medially deviated thumbs and great toes. We present a case of a 12-monthsold male infant with PS type 2 who underwent a craniosynostosis and advancing a supraorbital bar operations during general anesthesia. For simple procedures, a safe anesthetic plan can be formulated if the anatomic factors affecting the airway are carefully considered. More extensive and prolonged patient diagnosed to have PS require more monitoring and include all the problems associated with difficult intubation, hazardous airway management, massive blood loss and fluid shift, shunt-dependent hydrocephalus, and long anesthetic times. This case is presented since anaesthesiologists should be aware of the high incidence of respiratory and cranial complications in PS.

Differential diagnosis of multiple vertebral compression: butterfly vertebrae.

[Purpose] A butterfly vertebra is a rare congenital anomaly resulting from a symmetric fusion defect. Only a few cases of butterfly vertebra have been described. This anomaly may be isolated or associated with Pfeiffer, Jarcho-Levins, Crouzon, or Alagille syndrome. [Subject and Methods] We herein describe a 38-year-old man who presented with neck and low back pain and was found to have butterfly vertebrae at the T9 and L3 levels. He also had Behçet’s disease and psoriasis. [Results] The patient’s symptoms improved with analgesics and physiotherapy. [Conclusion] To our knowledge, butterfly vertebrae at two levels have never been reported. Butterfly vertebrae may be confused with vertebral fractures in lateral radiographs, and awareness of this anomaly is important for a correct diagnosis.

An Update on Midface Advancement Using Le Fort II and III Distraction Osteogenesis.

Le Fort II and III distraction osteogenesis (DO) is a powerful tool in the craniofacial armamentarium that is most often employed to treat patients with craniofacial syndromes such as Crouzon, Apert, or Pfeiffer syndrome who present with midfacial retrusion, shallow orbits, exorbitism, malocclusion, obstructive sleep apnea and facial imbalance. In this article, the authors will provide the reader with an update on techniques for the treatment of various forms of midfacial retrusion.

Earlier evidence of spheno-occipital synchondrosis fusion correlates with severity of midface hypoplasia in patients with syndromic craniosynostosis.

The spheno-occipital synchondrosis is an important driver of facial and cranial base growth. The current study characterizes its fusion in patients with Apert, Crouzon, and Pfeiffer syndromes and correlates early fusion with the presence, and degree, of midface hypoplasia. A retrospective case-control study was performed of all syndromic patients treated between 1996 and 2012. Case computed tomographic scans and age- and sex-matched control scans were analyzed as demonstrating either open, partially fused, or completely fused synchondroses, and patient age at each scan was recorded. Midface hypoplasia as determined by sella-nasion-A point angle measurement at the time of midface surgery was correlated to fusion status. Fifty-four patients with 206 computed tomographic scans met inclusion criteria. Two hundred six age- and sex-matched control scans were also identified. Average age at computed tomographic scanning was 6.1 years. The earliest ages of partial and complete fusion were 1.1 and 7.0 years, respectively, among cases; and 6.2 and 12.7 years, respectively, among controls. The odds of synchondrosis fusion in case computed tomographic scans was 66.0 times that of controls (95 percent CI, 9.2 to 475.5 times that of controls; p < 0.000001). Average age of synchondrosis fusion was 3.5 years (range, 0.5 to 6.0 years). Average sella-nasion-A point angle at the time of midface surgery was 67.5 degrees (range, 58 to 76 degrees), with a positive correlation between earlier age of fusion and more severe midface hypoplasia (p = 0.028). The spheno-occipital synchondrosis fuses earlier in syndromic patients compared with age-matched controls. Moreover, there is a positive correlation between earlier fusion and degree of midface hypoplasia, although definitive causality cannot be concluded. This is the first study to demonstrate such a correlation in human subjects. Risk, II.

P24.09: Pfeiffer type II syndrome diagnosed with three‐dimensional ultrasound and HD Live

Pfeiffer syndrome is an autosomal dominant acrocephalosyndactyly with three clinical subtypes. Type 2 is usually a de novo mutation with poor prognosis. It consists of acrocephaly, craniosynostosis, cloverleaf skull, broad thumb and hallux, brachydactyly and variable syndactyly. Facial dysmorphism is prominent with ocular proptosis, hypertelorism and depressed nasal bridge. Various associated visceral malformations are often encountered. We present a case of prenatally diagnosed Pfeiffer syndrome Type 2 with three-dimensional ultrasound and HD Live. A 28 year-old gravida 1 was referred to our center at 28 w.g. with a suspicion of a polymalformation syndrome. The detailed fetal morphology survey revealed a viable fetus in breech presentation with a cloverleaf skull, semilobar holoprosencephaly, prominent facial dysmorphism - exophthalmos and hypertelorism, macroglossia, depressed nasal bridge, totally distorted spine, big thumb and hallux, associated with remarked IUGR and polyhydramnios. The prenatal diagnosis of Pfeiffer syndrome Type II was suspected. Due to the poor prognosis the patient opted for termination of pregnancy. The prenatal sonographic findings were confirmed at autopsy. Conclusion: Three-dimensional ultrasound with HD Live provides excellent visualisation of the fetal face. Thus, any pathological condition affecting the fetal face can be more easily identified and explained to the parents. Obviously, this improves the prenatal diagnosis process and delineates better the pregnancy management plan in selected cases.

Pfeiffer syndrome: clinical and genetic findings in five Brazilian families.

Pfeiffer syndrome (PS) is mainly characterized by craniosysnostosis, midface hypoplasia, great toes with partial syndactyly of the digits and broad and medially deviated thumbs. It is caused by allelic mutations in the fibroblast growth factor receptor 1 and 2 (FGFR1 and 2) genes. This study describes the clinical and genetic features of five Brazilian families affected by PS. All patients exhibited the classical phenotypes related to PS. The genetic analysis was able to detect the mutations Cys278Phe, Cys342Arg, and Val359Leu in three of these families. Two mutations were de novo, with one familial. We identified pathogenic mutations in four PS cases in five Brazilian families by PCR sequencing of FGFR1 exon 5 and FGFR2 exons 5, 8, 10, 11, 15, and 16. The clinical and genetic aspects of these families confirm that this syndrome can be clinically variable, with different mutations in the FGFR2 responsible for PS. Key words:Craniosynostosis, Pfeiffer syndrome, mutation, FGFR2.

Craniofacial syndromes.

After studying this article, the participant should be able to: 1. Recognize the clinical presentations of commonly seen craniofacial syndromes. 2. Understand the most serious complications associated with each syndrome. 3. Formulate the best age-appropriate surgical plans. Craniofacial syndromes fall into two major categories-those associated with craniosynostosis, and those associated with clefts. Each has a different set of potential complications requiring a unique approach for surgical management. Craniosynostosis is a congenital disorder in which one or more of the cranial sutures fuses prematurely. The most common syndromes associated with this condition include Crouzon, Apert, Pfeiffer, Muenke, and Saethre-Chotzen syndromes. Surgical management of these children requires a multidisciplinary approach and close involvement of the family. Operations must take into consideration the growing potential of the bony structures. Common syndromes associated with clefts include Pierre Robin, Treacher Collins, Nager, Binder, and Stickler syndromes. Many of these children have severe airway issues requiring immediate address before operative reconstruction. As with syndromes associated with craniosynostosis, the key to management is a multidisciplinary approach focused on the right timing. The purpose of this article is to review the clinical presentation, care, and treatment of these patients.

Upper extremity anomalies in Pfeiffer syndrome and mutational correlations.

Pfeiffer syndrome is characterized by craniosynostosis and a variety of associated upper and lower extremity anomalies. The authors reviewed presentation and treatment of upper extremity anomalies in a series of genotyped patients with Pfeiffer syndrome. Medical records of patients with Pfeiffer syndrome seen at the authors' institution over a 16-year period were reviewed. Data on clinical presentation, genetic testing, and treatment were collected. The upper extremity anomalies were documented using plain radiographs and physical examinations by a multidisciplinary craniofacial team. Of 15 patients identified as having FGFR1- or FGFR2-confirmed Pfeiffer syndrome, 12 (80 percent) presented with upper extremity anomalies, most commonly broad thumbs [n = 10 (83 percent)], radial clinodactyly (thumbs) [n = 7 (58 percent)], and symphalangism [n = 7 each (58 percent)]. All patients with upper extremity anomalies had lower extremity anomalies. Six of the 12 patients (50 percent) with upper extremity findings underwent surgical correction. FGFR1 or FGFR2 genotype did not correlate with upper extremity phenotype. Although broad thumbs are common, patients with Pfeiffer syndrome often present with other upper extremity anomalies that may not require surgical intervention. Genetic and allelic heterogeneity may explain phenotypic variability in these upper extremity anomalies. Characterization of these limb differences should be made by pediatric hand surgeons as part of a craniofacial team. Treatment decisions should be individualized and dictated by the type and severity of clinical presentation. Risk, IV.

Quantification of facial skeletal shape variation in fibroblast growth factor receptor‐related craniosynostosis syndromes

fibroblast growth factor receptor (FGFR) -related craniosynostosis syndromes are caused by many different mutations within FGFR-1, 2, 3, and certain FGFR mutations are associated with more than one clinical syndrome. These syndromes share coronal craniosynostosis and characteristic facial skeletal features, although Apert syndrome (AS) is characterized by a more dysmorphic facial skeleton relative to Crouzon (CS), Muenke (MS), or Pfeiffer syndromes. Here we perform a detailed three-dimensional evaluation of facial skeletal shape in a retrospective sample of cases clinically and/or genetically diagnosed as AS, CS, MS, and Pfeiffer syndrome to quantify variation in facial dysmorphology, precisely identify specific facial features pertaining to these four syndromes, and further elucidate what knowledge of the causative FGFR mutation brings to our understanding of these syndromes. Our results confirm a strong correspondence between genotype and facial phenotype for AS and MS with severity of facial dysmorphology diminishing from Apert FGFR2(S252W) to Apert FGFR2(P253R) to MS. We show that AS facial shape variation is increased relative to CS, although CS has been shown to be caused by numerous distinct mutations within FGFRs and reduced dosage in ERF. Our quantitative analysis of facial phenotypes demonstrate subtle variation within and among craniosynostosis syndromes that might, with further research, provide information about the impact of the mutation on facial skeletal and nonskeletal development. We suggest that precise studies of the phenotypic consequences of genetic mutations at many levels of analysis should accompany next-generation genetic research and that these approaches should proceed cooperatively.

Pfeiffer Syndrome: Clinical and Genetic Analysis of the Three Families

This study described the clinical and genetic features of four patients from three Brazilian families affected by Pfeiffer syndrome. Methods: FGFR1 (exon 7 and 8) and FGFR2 (exon 10) were amplified by polymerase chain reaction sequencing. Results: All patients demonstrated the classical phenotypes related to Pfeiffer syndrome, such as brachycephaly, midface hypoplasia, flat forehead, proptosis, hypertelorism, short nose with a bulbous tip, broad and deviated thumbs, and big toes. Bilateral hearing loss and cleft palate were also observed in some members. The three families showed different mutations. In the first family, T1024C was in the exon 10 of FGFR2; in the second family, G833T in the exon 8 of FGFR2; and in the third family, G1075C in the exon 10 of FGFR2. Conclusion: The identification of clinical features associated with mutation analysis is important to correctly diagnose Pfeiffer syndrome and distinguish it from other clinically similar craniosynostosis syndromes.

Clinicogenetic Study of Turkish Patients With Syndromic Craniosynostosis and Literature Review

BackgroundFibroblast growth factor receptor 2 mutations have been associated with the craniosynostotic conditions of Apert, Crouzon, Pfeiffer, Saethre-Chotzen, Jackson-Weiss, Beare-Stevenson cutis gyrata, and Antley-Bixler syndromes in various ethnic groups. MethodsThirty-three unrelated Turkish patients (12 with Apert syndrome, 14 with Crouzon syndrome, six with Pfeiffer syndrome, and one with Saethre-Chotzen syndrome) and 67 nonsyndromic craniosynostosis patients were screened for mutations in exons IIIa and IIIc of the FGFR2 gene by denaturing high-performance liquid chromatography and confirmed by direct sequencing. ResultsWe detected several pathogenic mutations in 11/33 (33%) patients with Apert syndrome (four with p.Pro253Arg; seven with p.Ser252Trp) and 8/33 (24%) patients with Crouzon syndrome (three with p.Trp290Arg, one with p.Cys342Tyr, p.Cys278Phe, p.Gln289Pro, and a novel p.Tyr340Asn mutation) and five (15%) with Pfeiffer syndrome (p.Cys342Arg, p.Pro253Arg, p.Trp290Arg, and p.Ser351Cys). No FGFR2 gene mutation was detected in any of the patients with Saethre-Chotzen syndrome and nonsyndromic craniosynostosis. ConclusionsOur results indicate that the majority of Turkish patients with syndromic craniosynostosis have detectable genetic changes with an overall frequency of 72.7%. Because this is the first molecular genetic report from a Turkish cohort, the identified spectrum profile of FGFR2 mutations of the syndromic craniosynostotic patients would be very helpful for understanding the genotype–phenotype relationship and has a great value for diagnosis, prognosis, and genetic counseling.