Pfeiffer Syndrome with Extreme Proptosis, Hypothyroidism and Tail like Appendage.
Ontology highlight
ABSTRACT:
SUBMITTER: Soundaram V
PROVIDER: S-EPMC6451752 | biostudies-literature | 2014 Sep
REPOSITORIES: biostudies-literature
Publications
Pfeiffer Syndrome with Extreme Proptosis, Hypothyroidism and Tail like Appendage.
Soundaram V V Lewis Leslie E LE Girisha K M KM Jayashree P P Balasubramanian S S Pratyusha R R
Oman medical journal 20140901 5
Pfeiffer syndrome is a rare genetic disorder with combination of bicoronal craniosynostosis, broad thumbs, broad great toes, ankylosis of elbow and partial variable syndactyly of the hands and feet. Since the disorder was reported by Pfeiffer in 1964, new associations have been added on. Authors report a newborn with features of Pfeiffer syndrome type 3 with hypothyroidism, tail like appendage and extremely anteriorly placed anus as new associations. ...[more]
Similar Datasets
Project description:Pfeiffer syndrome is a rare autosomal dominantly inherited disorder that associates craniosynostosis, broad and deviated thumbs and big toes, and partial syndactyly on hands and feet. Hydrocephaly may be found occasionally, along with severe ocular proptosis, ankylosed elbows, abnormal viscera, and slow development. Based on the severity of the phenotype, Pfeiffer syndrome is divided into three clinical subtypes. Type 1 "classic" Pfeiffer syndrome involves individuals with mild manifestations including brachycephaly, midface hypoplasia and finger and toe abnormalities; it is associated with normal intelligence and generally good outcome. Type 2 consists of cloverleaf skull, extreme proptosis, finger and toe abnormalities, elbow ankylosis or synostosis, developmental delay and neurological complications. Type 3 is similar to type 2 but without a cloverleaf skull. Clinical overlap between the three types may occur. Pfeiffer syndrome affects about 1 in 100,000 individuals. The disorder can be caused by mutations in the fibroblast growth factor receptor genes FGFR-1 or FGFR-2. Pfeiffer syndrome can be diagnosed prenatally by sonography showing craniosynostosis, hypertelorism with proptosis, and broad thumb, or molecularly if it concerns a recurrence and the causative mutation was found. Molecular genetic testing is important to confirm the diagnosis. Management includes multiple-staged surgery of craniosynostosis. Midfacial surgery is performed to reduce the exophthalmos and the midfacial hypoplasia.
| S-EPMC1482682 | biostudies-literature
Project description:Pfeiffer syndrome (PS) is mainly characterized by craniosysnostosis, midface hypoplasia, great toes with partial syndactyly of the digits, 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.
| S-EPMC4320421 | biostudies-literature
Project description:Crouzon syndrome and Pfeiffer syndrome are both autosomal dominant craniosynostotic disorders that can be caused by mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. To determine the parental origin of these FGFR2 mutations, the amplification refractory mutation system (ARMS) was used. ARMS PCR primers were developed to recognize polymorphisms that could distinguish maternal and paternal alleles. A total of 4,374 bases between introns IIIa and 11 of the FGFR2 gene were sequenced and were assayed by heteroduplex analysis, to identify polymorphisms. Two polymorphisms (1333TA/TATA and 2710 C/T) were found and were used with two previously described polymorphisms, to screen a total of 41 families. Twenty-two of these families were shown to be informative (11 for Crouzon syndrome and 11 for Pfeiffer syndrome). Eleven different mutations in the 22 families were detected by either restriction digest or allele-specific oligonucleotide hybridization of ARMS PCR products. We molecularly proved the origin of these different mutations to be paternal for all informative cases analyzed (P=2. 4x10-7; 95% confidence limits 87%-100%). Advanced paternal age was noted for the fathers of patients with Crouzon syndrome or Pfeiffer syndrome, compared with the fathers of control individuals (34. 50+/-7.65 years vs. 30.45+/-1.28 years, P<.01). Our data on advanced paternal age corroborates and extends previous clinical evidence based on statistical analyses as well as additional reports of advanced paternal age associated with paternal origin of three sporadic mutations causing Apert syndrome (FGFR2) and achondroplasia (FGFR3). Our results suggest that older men either have accumulated or are more susceptible to a variety of germline mutations.
| S-EPMC1288162 | biostudies-literature
Project description:Pfeiffer syndrome (PS) is a rare autosomal dominant genetic disorder characterized by craniosynostosis, broad thumbs / toes. Here, we report a case of PS type 2 with increased nuchal translucency in early trimester.
| S-EPMC8543055 | biostudies-literature
Project description:Pfeiffer syndrome (PS) is an autosomal dominant disorder with three subtypes stemming from heterozygous mutations in the fibroblast growth factors FGFR1 and FGFR2. The subtypes overlap with heterogeneous clinical manifestations and variable prognosis dependent on neurological and respiratory compromise that impact short- and long-term outcomes and survival. We present a male, term infant with type II PS that was diagnostically suspected antenatally based on three-dimensional ultrasonographic findings that were confirmed postnatally by craniofacial tomography and magnetic resonance imaging. A new generation sequencing panel identified a unique de novo FGFR2, c.335 A > G p. Tyr112Cys variant, the first of its kind, and features that closely aligned with subtype II PS. Initial molecular results categorized the mutation as nonpathogenic, but it was later reclassified as pathogenic. Antenatal, multidisciplinary parental counseling about the tentative diagnosis and prognosis facilitated postnatal decisions that culminated in an informed choice for palliative care and early demise.
| S-EPMC9537020 | biostudies-literature
Project description:Objective: To report the clinical and radiographic findings and molecular etiology of the first monozygotic twins affected with Pfeiffer syndrome. Methods: Clinical and radiographic examination and whole exome sequencing were performed on two monozygotic twins with Pfeiffer syndrome. Results: An acceptor splice site mutation in FGFR2 (c.940-2A>G) was detected in both twins. The father and both twins shared the same haplotype, indicating that the mutant allele was from their father’s chromosome who suffered severe upper airway obstruction and subsequent obstructive sleep apnea. Hypertrophy of nasal turbinates appears to be a newly recognized finding of Pfeiffer syndrome. Increased intracranial pressure in both twins were corrected early by fronto-orbital advancement with skull expansion and open osteotomy, in order to prevent the more severe consequences of increased intracranial pressure, including hydrocephalus, the bulging of the anterior fontanelle, and the diastasis of suture. Conclusions: Both twins carried a FGFR2 mutation and were discordant for lambdoid synostosis. Midface hypoplasia, narrow nasal cavities, and hypertrophic nasal turbinates resulted in severe upper airway obstruction and subsequent obstructive sleep apnea in both twins. Hypertrophy of the nasal turbinates appears to be a newly recognized finding of Pfeiffer syndrome. Fronto-orbital advancement with skull expansion and open osteotomy was performed to treat increased intracranial pressure in both twins. This is the first report of monozygotic twins with Pfeiffer syndrome.
| S-EPMC9601734 | biostudies-literature
Project description:RationaleNeurofibromatosis type 1 (NF1) is a hereditary disease characterized by café-au-lait spots, peripheral neurofibromas, Lisch nodules, optic nerve glioma, and sphenoid wing dysplasia. Pulsating proptosis is associated with a sphenoid bony defect. Heavy eye syndrome is characterized by acquired esohypotropia in patients with high myopia. This study aimed to describe the presentation of pulsating proptosis and heavy eye syndrome precipitated by NF1 and its management.Patient concernsA 41-year-old woman presented with progressive pulsating proptosis and hypodeviation of the right eye over the past 2 years. The axial length of the right eye was 36.81 mm. The right eye presented with esohypotropia and hypoglobus. The ocular motility examination showed limitations in all directions, especially in supraduction. Brain computed tomography revealed sphenoid wing dysplasia of the right orbit. The meningocele protruded through the orbital defect, lifting the globe. Brain magnetic resonance imaging demonstrated superior rectus muscle (SR) medial displacement and lateral rectus muscle inferior displacement. Physical examination revealed café-au-lait macules and neurofibromas on the trunk.DiagnosisNF1 with pulsating proptosis and heavy eye syndrome.InterventionsThe patient declined neurosurgery due to risk and economic reasons. To manage her main concern regarding cosmetics, we performed orbital floor decompression, SR resection with advancement, maximal hang-back recession of the inferior rectus muscle, and a partial Jensen's procedure.OutcomesProptosis was reduced. The eye position became more symmetrical. The range of eye movements was also increased.LessonsThis case describes a rare synchronous presentation of pulsating proptosis and heavy eye syndrome precipitated by NF1. Adult-onset presentation implied a progressive process in NF1. The case also showed a different etiology from that of typical heavy eye syndrome. It reminds ophthalmologists that orbital imaging should be performed in high myopia patients with strabismus to evaluate the extraocular muscle pathway. Furthermore, the case demonstrated a management that avoided the risk and expensive cost of neurosurgery, which has not been reported.
| S-EPMC8542118 | biostudies-literature
Project description:Abstract Backgrounds Craniosynostosis syndrome has a variety of causes, one of which is an autosomal dominant disorder associated with FGFR1 or FGFR2 gene mutation known as Pfeiffer syndrome (PS; OMIM 101600). It is known that PS is clinically diagnosed, not genetic judgment. PS is divided into three subtypes depending on severity of specific phenotypes. Patients with PS type 1 are broad thumbs and great toes, brachydactyly or syndactyly. They have widely spaced eyes, midface hypoplasia and dental abnormalities but short stature is not typical phenotype of PS. We report the patient who were clinically diagnosed PS with short stature because of growth hormone deficiency (GHD). Case Report: A 4 years 7 month-old girl presented with a short stature below the 3rd percentile. She was born at 40 weeks of gestation with a birth weight of 2.9 kg. Her perinatal and neonatal histories were unremarkable. Her parents are non-consanguineous and her mother had micro- pituitary adenoma. She has healthy younger brother who aged 9 months old. In physical examination, height was 91.1 cm (-3.92 SDS), weight was 15.5 kg (-1.15 SDS). Wide thumb and great toes on both sides of her are observed. At the time of admission, bone age was advanced, measured 7 years. There were no specific findings other than a decrease in IGF-1 level (108.24 ng/ml) and increase in prolactin level (27.26 ng/ml) on the basic endocrine examination. The growth hormone (GH) induced stimulation test was performed after admission. She underwent GH induced stimulation test with combinations of 2 stimulants to assess GH secretion: levodopa 150 mg and arginine 0.5 g/kg. The peak GH level was 7.41 ng/ml in levodopa test and 5.58 ng/ml after 30 minutes’ response to arginine. She was diagnosed as a partial GHD defined by peak GH between 5 and 10 ng/ml in both test. There were no findings in karyotyping and chromosomal microarray. As a result of targeted panel sequencing of 233 genes related to hereditary short stature, c.2398dupT, a pathogenic variant that had not been previously reported in the FGFR2 gene, was observed in a heterozygous form as the cause of short stature. Subsequently, recombinant human GH has been administered in units of 0.1 per day according to her weight. The height was increased from 93.6 cm (SDS) in 4 years 10 months old to 98 cm in 5 years 2 months. Any side effects or adverse reactions were not observed during the treatment period. Conclusion It is suggested that a growth hormone test be performed for Pfeiffer syndrome patients with short stature. GH may help growth in patients with positive in the test. Presentation: No date and time listed
| S-EPMC9625759 | biostudies-literature
Project description:We present a case of a 79-year-old man with a non-symptomatic pulsatile proptosis of the left eye. Magnetic resonance imaging revealed a meningocele into the left orbit due to an osseous defect in the orbital roof.
| S-EPMC5474481 | biostudies-literature
Project description:Pfeiffer syndrome is an autosomal dominant condition classically combining craniosynostosis with digital anomalies of the hands and feet. The majority of cases are caused by heterozygous mutations in the third immunoglobulin-like domain (IgIII) of FGFR2, whilst a small number of cases can be attributed to mutations outside this region of the protein. A mild form of Pfeiffer syndrome can rarely be caused by a specific mutation in FGFR1. We report on the clinical and genetic findings in a three generation British family with Pfeiffer syndrome caused by a heterozygous missense mutation, p.Ala172Phe, located in the IgII domain of FGFR2. This is the first reported case of this particular mutation since Pfeiffer's index case, originally described in a German family in 1964, on which basis the syndrome was eponymously named. Genetic analysis demonstrated the two families to be unrelated. Similarities in phenotypes between the two families are discussed. Independent genetic origins, but phenotypic similarities in the two families add to the evidence supporting the theory of selfish spermatogonial selective advantage for this rare gain-of-function FGFR2 mutation.
| S-EPMC3652025 | biostudies-literature