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Orphanet Journal of Rare Diseases Jun 2006Pfeiffer syndrome is a rare autosomal dominantly inherited disorder that associates craniosynostosis, broad and deviated thumbs and big toes, and partial syndactyly on... (Review)
Review
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.
Topics: Acrocephalosyndactylia; Fingers; Genes, Dominant; Humans; Mutation; Receptor, Fibroblast Growth Factor, Type 1; Receptor, Fibroblast Growth Factor, Type 2; Toes
PubMed: 16740155
DOI: 10.1186/1750-1172-1-19 -
Child's Nervous System : ChNS :... Feb 2021Pfeiffer syndrome (PS) is a rare autosomal dominant craniofacial disorder characterized by primary craniosynostosis, midface hypoplasia, and extremities' abnormalities... (Review)
Review
Pfeiffer syndrome (PS) is a rare autosomal dominant craniofacial disorder characterized by primary craniosynostosis, midface hypoplasia, and extremities' abnormalities including syndactyly. The purpose of this article was to review the current knowledge regarding how PS affects the nervous system. Methodologically, we conducted a systematic review of the existing literature concerning involvement of the nervous system in PS. Multiple-suture synostosis is common, and it is the premature fusion and abnormal growth of the facial skeleton's bones that cause the characteristic facial features of these patients. Brain abnormalities in PS can be primary or secondary. Primary anomalies are specific developmental brain defects including disorders of the white matter. Secondary anomalies are the result of skull deformity and include intracranial hypertension, hydrocephalus, and Chiari type I malformation. Spinal anomalies in PS patients include fusion of vertebrae, "butterfly" vertebra, and sacrococcygeal extension. Different features have been observed in different types of this syndrome. Cloverleaf skull deformity characterizes PS type II. The main neurological abnormalities are mental retardation, learning difficulties, and seizures. The tricky neurological examination in severely affected patients makes difficult the early diagnosis of neurological and neurosurgical complications. Prenatal diagnosis of PS is possible either molecularly or by sonography, and the differential diagnosis includes other craniosynostosis syndromes. Knowing how PS affects the nervous system is important, not only for understanding its pathogenesis and determining its prognosis but also for the guidance of decision-making in the various critical steps of its management. The latter necessitates an experienced multidisciplinary team.
Topics: Acrocephalosyndactylia; Brain; Craniosynostoses; Facial Bones; Humans; Hydrocephalus
PubMed: 33083874
DOI: 10.1007/s00381-020-04934-7 -
Child's Nervous System : ChNS :... Sep 2019Pfeiffer syndrome is a rare autosomal dominant inherited disorder associated with craniosynostosis, midfacial hypoplasia, and broad thumbs and toes. The syndrome has... (Review)
Review
INTRODUCTION
Pfeiffer syndrome is a rare autosomal dominant inherited disorder associated with craniosynostosis, midfacial hypoplasia, and broad thumbs and toes. The syndrome has been divided into three clinical subtypes based on clinical findings.
METHODS
This review will specifically examine the most severe type, Pfeiffer syndrome type 2, focusing on its genetics and molecular biology.
CONCLUSION
This subtype of the syndrome is caused by de novo sporadic mutations, the majority of which occur in the fibroblast growth factor receptor type 1 and 2 (FGFR1/2) genes. There is not one specific mutation, however. This disorder is genetically heterogeneous and may have varying phenotypic expressions that in various cases have overlapped with other similar craniosynostoses. A specific missense mutation of FGFR2 causing both Pfeiffer and Crouzon syndromes has been identified, with findings suggesting that gene expression may be affected by polymorphism within the same gene. Compared to other craniosynostosis-related disorders, Pfeiffer syndrome is the most extreme phenotype, as the underlying mutations cause wider effects on the secondary and tertiary protein structures and exhibit harsher clinical findings.
Topics: Acrocephalosyndactylia; Genotype; Humans; Phenotype; Receptor, Fibroblast Growth Factor, Type 1; Receptor, Fibroblast Growth Factor, Type 2
PubMed: 31222448
DOI: 10.1007/s00381-019-04244-7 -
Optometry (St. Louis, Mo.) Jul 2005In 1964, Pfeiffer described a three-generation family in which eight individuals had a syndrome consisting of craniosynostosis, broad thumbs and great toes, and partial... (Review)
Review
BACKGROUND
In 1964, Pfeiffer described a three-generation family in which eight individuals had a syndrome consisting of craniosynostosis, broad thumbs and great toes, and partial syndactyly of the hands and feet. Pfeiffer syndrome affects males and females equally, and is most commonly a result of de novo mutations, but can be inherited in an autosomal dominant fashion. Pfeiffer syndrome is considered Type V of the five acrocephalosyndactly syndromes (ACS), a group of rare genetic diseases that involve premature closure of the cranial sutures. Cohen, in 1993, further described Pfeiffer syndrome and it's various expression patterns by creating three subgroups of the syndrome.
CONCLUSIONS
While Pfeiffer syndrome is clearly a rare disorder, affecting 15 of every 1 million births, there has been a series of publications reviewing the difficult differential diagnosis among Pfeiffer types and between the other acrocephalosyndactly syndromes. While these publications individually focus on a variety of specific systemic and ocular implications of the syndrome, together they encompass the scope of the syndrome. Since Pfeiffer syndrome mainly affects the craniofacial regions, the eye care professional plays an essential role in diagnosis and management. What follows are guidelines to aid in the diagnosis, ophthalmic and functional testing, and management of this disorder.
Topics: Acrocephalosyndactylia; Eye Diseases, Hereditary; Humans
PubMed: 16038862
DOI: 10.1016/j.optm.2005.05.002 -
The Journal of Maternal-fetal &... Sep 2017Pfeiffer syndrome (PS) is an autosomal dominant disorder caused by mutations in FGFR1 and FGFR2 genes. Given its wide range of clinical expression and severity, early... (Review)
Review
PURPOSE
Pfeiffer syndrome (PS) is an autosomal dominant disorder caused by mutations in FGFR1 and FGFR2 genes. Given its wide range of clinical expression and severity, early prenatal diagnosis is difficult and genetic counseling is desirable. We report a literature review of all prenatal diagnosis of PS and a case report, with a focused description of ultrasound findings.
METHODS
After literature search, we selected 14 studies of antenatal diagnosis of PS. Prenatal ultrasound findings, outcome, maternal and obstetrical data and genetic tests were recorded and analyzed.
RESULTS
A total of 18 cases including the one we present were selected. Among the most frequent sonographic features, skull shape anomalies were evident in 72.2% of cases, nasal abnormalities in 50%, proptosis and hypertelorism in 44.4% and frontal bossing in 22.2%. Thumbs' anomalies were present in 33.3% of cases and toes' abnormalities in 38.9%. In all cases, postnatal or postmortem examination confirmed the prenatal diagnosis of PS.
CONCLUSIONS
We provide a literature review of prenatal diagnosis of PS to identify ultrasound features that may be supportive in the diagnosis of this rare disease, helping in making a differential diagnosis with the other possible craniosynostosis syndromes and in suggesting gene molecular testing.
Topics: Abortion, Eugenic; Acrocephalosyndactylia; Adult; Diagnosis, Differential; Female; Gestational Age; Humans; Karyotyping; Limb Deformities, Congenital; Magnetic Resonance Imaging; Mutation; Prenatal Diagnosis; Radiography; Receptor, Fibroblast Growth Factor, Type 1; Receptor, Fibroblast Growth Factor, Type 2; Skull; Ultrasonography; Young Adult
PubMed: 27762162
DOI: 10.1080/14767058.2016.1243099 -
The Cleft Palate-craniofacial Journal :... Jun 2022Pfeiffer syndrome is one of the autosomal dominant craniofacial syndromes. Classical clinical manifestations are coronal suture synostosis causing brachycephaly, midface...
Pfeiffer syndrome is one of the autosomal dominant craniofacial syndromes. Classical clinical manifestations are coronal suture synostosis causing brachycephaly, midface retrusion, airway compromise, broad thumbs, and toes. Pfeiffer syndrome type I (classic type) is associated with mutation. However, wide range of clinical manifestations, with and without craniosynostosis, have been reported. Here, we present a family of Pfeiffer syndrome across 3 generations with identical : c.755C>G (p.Pro252Arg) mutation. Where the members of the youngest generation have no cranial involvement. Lastly, we propose a guideline management for familial Pfeiffer syndrome management.
Topics: Acrocephalosyndactylia; Craniosynostoses; Humans; Mutation; Patient Care Team; Skull
PubMed: 34238036
DOI: 10.1177/10556656211028505 -
The Journal of Maternal-fetal &... Dec 2022We report a rare case of autosomal dominant genetic syndrome "Pfeiffer", which is part of the group of acrocephalosyndactyly, with an annual incidence <1/100,000. Three... (Review)
Review
We report a rare case of autosomal dominant genetic syndrome "Pfeiffer", which is part of the group of acrocephalosyndactyly, with an annual incidence <1/100,000. Three forms are known. Type I is the less common form and it is characterized by moderate-severe mediofacial hypoplasia usually with normal cognitive development. Conversely, types 2 and 3 are more common and they are associated with more severe signs and complications with a more unfavorable prognosis. The type 3 form due to the presence of a cloverleaf skull distinguishes type 2. Thirty-eight-year-old primigravida was referred to our center, at 28 weeks of gestation due to borderline ventriculomegaly, macrocrania, and a short femur. First trimester screening for chromosomopathies and CF-DNA was low risk; II trimester screening ultrasound showed the presence of "short femur" and macrocrania. Our ultrasound evaluation, assisted by 3D ultrasound, showed cloverleaf skull, turricephaly, moderate ventriculomegaly (13 mm), hypertelorism and exophthalmos, low ear implantation, mild rhizomelia. Ultrasound depicts Pfeiffer syndrome or other acrocephalosyndactyly syndromes (Apert syndromes, Saethre-Chotzen) or other syndromic forms of craniosynostosis like Crouzon syndrome. The NGS panel for molecular analysis of genes involved in skeletal dysplasias showed the mutation of the FGFR2 gene, . Using three-dimensional (3D) ultrasound, it is easier to distinguish rare syndromes characterized by facial dysmorphisms such as exophthalmos, mediofacial hypoplasia, and craniosynostosis.
Topics: Pregnancy; Female; Humans; Adult; Acrocephalosyndactylia; Syndrome; Craniosynostoses; Prenatal Diagnosis; Hydrocephalus; Exophthalmos
PubMed: 34182859
DOI: 10.1080/14767058.2021.1937984 -
Plastic and Reconstructive Surgery Apr 2022Visual impairment secondary to orbital and periorbital dysmorphology is frequent in Pfeiffer syndrome patients. The etiopathogenesis of this aberrancy, however, remains...
BACKGROUND
Visual impairment secondary to orbital and periorbital dysmorphology is frequent in Pfeiffer syndrome patients. The etiopathogenesis of this aberrancy, however, remains unclear.
METHODS
Untreated Pfeiffer syndrome patients (n = 31) and normal control subjects (n = 43) were compared. Craniometric and volumetric analyses related to the orbital and periorbital anatomy were performed using Materialise (Leuven, Belgium) software.
RESULTS
Overall, orbital cavity volume of Pfeiffer patients is reduced by 28 percent (p < 0.001), compared to normal, starting before 3 months of age (p = 0.004). Globe volume was diminished by 10 percent (p = 0.041) before 3 months of age, yet tended to catch up thereafter. However, the retrobulbar soft-tissue volume remained smaller beyond 1 year of age (17 percent, p = 0.003). Globe volume projection beyond the bony orbit increased in all observed ages (82 percent, p < 0.001). The volumes of sphenoid bone, maxilla, and mandible proportionately were restricted by 24 to 25 percent (p = 0.003 to 0.035) before 3 months of age. The volume of maxilla and mandible gradually approximate normal; however, the sphenoid bone volume in Pfeiffer patients remains less than normal (p = 0.002) into childhood. The anteroposterior length of both the zygoma and the maxilla was reduced by 14 percent (p < 0.001). Anterior positioning of the zygoma is less by 23 percent (p < 0.001) in Pfeiffer patients overall, with anterior positioning of maxilla reduced similarly by 23 percent (p < 0.001).
CONCLUSIONS
Pfeiffer syndrome patients develop decreased retrobulbar soft-tissue and globe volume, along with a restricted orbital cavity volume in infancy. Significant hypoplasia of the sphenoid bone is associated with more severe central facial (maxilla) retrusion, compared to lateral facial structures (zygoma).
CLINICAL QUESTION/LEVEL OF EVIDENCE
Risk, II.
Topics: Acrocephalosyndactylia; Cephalometry; Child; Humans; Maxilla; Orbit; Zygoma
PubMed: 35171849
DOI: 10.1097/PRS.0000000000008928 -
Journal of Korean Medical Science Apr 2006Pfeiffer Syndrome is as rare as Apert syndrome in the Western population. This condition is very rare in the Asian population and has not been previously reported in... (Review)
Review
Pfeiffer Syndrome is as rare as Apert syndrome in the Western population. This condition is very rare in the Asian population and has not been previously reported in Korea. The authors report with a review of literature the case of a newborn baby with Pfeiffer syndrome, manifested by bicoronal craniosynostosis, broad thumbs, and big toes. The infant also had bilateral syndactyly of the fingers and toes, mild proptosis, choanal hypoplasia and maxillary hypoplasia.
Topics: Acrocephalosyndactylia; Female; Humans; Infant, Newborn; Korea; Radiography
PubMed: 16614535
DOI: 10.3346/jkms.2006.21.2.374 -
The Journal of the Association of... Sep 2020
Topics: Acrocephalosyndactylia; Case-Control Studies; Humans
PubMed: 32798349
DOI: No ID Found