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The Role of Genetic Mutations in Genes FGFR1 & FGFR2 in Pfeiffer

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The Role of Genetic Mutations in Genes FGFR1 & FGFR2 in Pfeiffer Open Access Journal of Pediatrics and Neonatal Medicine Volume 1 Issue 2 ISSN: 2694-5983 Case Report The Role of Genetic Mutations in Genes FGFR1 & FGFR2 in Pfeiffer Syndrome Amjadi H* Department of Division of Medical Genetics and Molecular Pathology Research, Harvard University, Boston Children's Hospital, USA Article Info Abstract Article History: Pfeiffer syndrome is a rare genetic disorder characterized by premature fusion of certain skull Received: 11 December 2019 bones (craniosynostosis), and abnormally broad and medially deviated thumbs and great toes. Accepted: 13 December 2019 Most affected individuals also have differences to their midface (protruding eyes) and Published: 17 December 2019 conductive hearing loss. Three forms of Pfeiffer syndrome are recognized, of which types II and III are the more serious. Pfeiffer syndrome is an autosomal dominant condition associated with *Corresponding author: Amjadi mutations in the genes fibroblast growth factor receptor-2 (FGFR2) and fibroblast growth factor H, University of South Florida, receptor-1 (FGFR1). Tampa, FL, United States. DOI: https://doi.org/10.36266/JPNM/110 Keywords: Pfeiffer syndrome; Genetics rare disorder; Genetics mutations; FGFR1; FGFR2 Genes Copyright: © 2019 Asadi S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. brain. Characteristic features of the head and face associated with Introduction type II Pfeiffer syndrome may include: abnormal forehead, severe Overview of Pfeiffer Syndrome ocular protopsy, hypoplasia of the mid-facial lesions, beak-shaped nose tip, and lower fracture of the ears. Also, some infants with Pfeiffer syndrome is a very rare genetic disorder that is associated type II Pfiffer may reveal abnormal skeletal abnormalities in the with premature fusion of certain bones of the skull organs or joints or specific internal organs in the abdomen (visceral (craniosinostosis), large and large fingers, especially the thumb, abnormalities) that may cause these infants to remain stable or protruding eyes and conductive hearing loss. Pfeiffer syndrome is inactive [1,4]. In addition, infants with type II Pfiffer may now known to be a member of a group of conditions caused by experience mental retardation and neurological problems due to mutations in the FGFR genes including Apert syndrome, Crouzon severe brain involvement or hypoxia due to respiratory problems. syndrome, Beare-Stevenson syndrome, FGFR2-related isolated Therefore, if proper and timely treatment is not provided in these coronal synostosis, and Jackson-Weiss syndrome, Crouzon infants, these factors can be life threatening during infancy [1,5]. syndrome with acanthosis nigricans and Muenke syndrome. (For People with type III Pfeiffer syndrome reveal the same symptoms more information on these conditions, please see the Related and findings as Pfeiffer type II, with the exception of skeletal Disorders section below) [1]. malignancy (clover leaf skull). Additional features in Type III Symptoms and Sings of Pfeiffer Syndrome Pfeiffer syndrome include: anterior cranial shortening, abnormal presence of certain teeth at birth (primary tooth), severe ocular Researchers have divided Pfeiffer syndrome into three groups: protrusion (proptosis), abnormal bone cavity (orbital orbit) or Pfeiffer syndrome 1, Pfeiffer Syndrome 2, Pfeiffer syndrome 3. visceral malformations. Patients with type II Pfeiffer syndrome, Neonates with type 1 Pfeiffer syndrome have craniosinostosis in like those with type II Patients, may also experience mental the head, which seems to be the size of the head, short and long retardation and severe neurological problems, and these disorders (brachial plexus). Additional features in these infants may include: can be life threatening in early life if they are not timely diagnosed prominent forehead, midfacial hypoplasia, wide-eyed (ocular and treated appropriately [1,6] (Figures 1-10). hypertension), and maxillary malfunction (maxillary hypoplasia), prominent mandible, and dental disorders [1,2]. Neonates with type The Etiology of Pfeiffer Syndrome 2 Pfeiffer syndrome are characterized by a more severe form of Pfeiffer type 1 is caused by mutations in the FGFR1 and FGFR2 craniosinostosis (severe clawed skull), severe abnormalities in the genes. The FGFR1 gene is located on the short arm of chromosome hands and feet, and additional abnormalities in the organs. In 8 at 8p11.23. The FGFR2 gene is located on the long arm of infants with type II Pfizer, premature closure of the fibrous joints chromosome 10 at 10q26.13. Pfeiffer type 2 and Pfeiffer syndrome (skull suture) between several bones in the skull causes the skull to are caused by FGFR2 gene mutation [1,7]. Pfeiffer type 1 follows form a three-lobe [1,3]. the dominant autosomal inherited pattern. Therefore, only one copy In addition, triple cranial lobes in neonates with type II Pfeiffer of the FGFR1 and FGFR2 mutant genes (parent or mother) is syndrome cause cerebrospinal fluid accumulation in the skull needed to cause this syndrome in the next generation, and the (hydrocephalus), which also results in increased pressure in the Pubtexto Publishers | www.pubtexto.com 1 J Paediatr Neonatol Citation: Amjadi H (2019) The Role of Genetic Mutations in Genes FGFR1 & FGFR2 in Pfeiffer Syndrome. J Paediatr Neonatal Med 1(2): 110 DOI: https://doi.org/10.36266/JPNM/110 chance of having a child with Pfeiffer syndrome is 50% for each genetic testing of the FGFR1 and FGFR2 genes to evaluate possible pregnancy. It should be noted that Pfeiffer syndrome type possible mutations [1,11-14]. II and Pfeiffer syndrome occur as a result of new mutations and do not follow any inheritance pattern. It is noteworthy that father age and parental environment are associated with an increased risk of new mutations in the FGFR1 and FGFR2 genes for their subsequent generation of Pfeiffer syndrome [1,8]. Figure 3: Picture of a child with type 2 Pfeiffer Syndrome, with a clover leaf skull and an elevation of the eyes. Figure 1: Picture of fetus with PTSD with prominent skull carniosinostosis. Figure 4: Other images of patients with type 2 Pfeiffer Syndrome. Figure 2: Picture of a child with type 1 Pfeiffer Syndrome, with an elevation of the eyes. Figure 5: Images of children with type 1,2,3 Pfeiffer Syndrome. Frequency of Pfeiffer Syndrome Pathways of Treatment in Pfeiffer Syndrome Pfeiffer syndrome affects men and women in equal numbers and The treatment of Pfeiffer syndrome is based on the symptoms that can occur in all races. The prevalence of all types of Pfeiffer each person manifests. Treatment may be coordinated by a team of syndrome worldwide is about 1 in 100,000 live births [1,9,10]. professionals such as: pediatricians, surgeons, neurologists, Diagnosis of Pfeiffer Syndrome ophthalmologists, ENT specialists, hearing specialists, molecular or medical geneticists, and other health care professionals. To Diagnosis of Pfeiffer syndrome is based on clinical findings. The correct the intracerebral pressure caused by hydrocephalus, most definitive diagnosis of Pfeiffer syndrome is by molecular additional cerebrospinal fluid can be discharged from the Pubtexto Publishers | www.pubtexto.com 2 J Paediatr Neonatol Citation: Amjadi H (2019) The Role of Genetic Mutations in Genes FGFR1 & FGFR2 in Pfeiffer Syndrome. J Paediatr Neonatal Med 1(2): 110 DOI: https://doi.org/10.36266/JPNM/110 Figure 6: Schematic view of chromosome 8 where the FGFR1 gene is located in the short arm of chromosome 8p11.23. Figure 7: Schematic overview of chromosome 10 where the FGFR2 gene is located in the long arm of chromosome 10q26.13. Figure 8: Schematic overview of the dominant autosomal inherited pattern, which also follows the pattern of Pfeiffer syndrome. Intracranial by inserting the shunt tube into the skull. Special may also help to remove the cavities (finger stickiness). surgery can also be used to correct mid - facial lesions, asymmetry Physiotherapy and orthopedic procedures may be used to help of the face, nasal disorders, ocular proptosis (ocular orbit). Hearing improve the mobility of patients with Pfeiffer syndrome. It is worth aids can be used to improve the hearing status of children with noting that early intervention is very important for treating or Pfeiffer syndrome. In some people with Pfeiffer syndrome, surgery improving the physical condition of Pfeiffer syndrome patients and Pubtexto Publishers | www.pubtexto.com 3 J Paediatr Neonatol Citation: Amjadi H (2019) The Role of Genetic Mutations in Genes FGFR1 & FGFR2 in Pfeiffer Syndrome. J Paediatr Neonatal Med 1(2): 110 DOI: https://doi.org/10.36266/JPNM/110 can play an important role in the fate of these patients. Genetic and, in the case of hydrocephalus, to insert a tube (shunt) to drain counseling is also important for all parents who have a family excess cerebrospinal fluid (CSF) away from the brain and into history of Pfeiffer syndrome or any other genetic damage, as well another part of the body where the CSF can be absorbed. Early as for families seeking a healthy child [1,15-18]. corrective and reconstructive surgery may also be performed in infants with Pfeiffer syndrome to help correct certain associated craniofacial abnormalities (e.g., midface hypoplasia, facial asymmetry, nasal abnormalities, ocular proptosis due to shallow orbits). The results of such craniofacial surgery may vary [1,20,21]. References 1. Asadi S, Jamali M, Bagheri R, Dell SS, Rad MT. Book of Pathology in Medical Genetics. Amidi Publications. 2017; 2. 2. National Institutes of Health. Genetic and Rare Diseases GARD. Information Center 2016-04-01. Pfeiffer syndrome. Symptoms. Retrieved. 2016. 3. Cohen MM. Pfeiffer syndrome update, clinical subtypes, and guidelines for differential diagnosis. Am J Med Genet. 1993; 45: 300- 307. 4. Muenke M, Schell U, Hehr A, Robin NH, Losken HW, Schinzel A, et al. A common mutation in the fibroblast growth factor receptor 1 Figure 9: Schematic view of the frequency map of the prevalence of gene in Pfeiffer syndrome. Nat Genet.
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