Pfeiffer syndrome

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Pfeiffer syndrome
Pfeiffer's syndrome type II with cloverleaf shaped skull and bilateral proptosis.png
Pfeiffer syndrome type 2 with cloverleaf-shaped skull and bilateral proptosis before and after surgery
Specialty Rheumatology   OOjs UI icon edit-ltr-progressive.svg
Causes Genetic [1]
Frequency1 per 100,000 births [1]
Named after Rudolf Arthur Pfeiffer

Pfeiffer syndrome is a rare genetic disorder, characterized by the premature fusion of certain bones of the skull (craniosynostosis), which affects the shape of the head and face. The syndrome includes abnormalities of the hands and feet, such as wide and deviated thumbs and big toes.

Contents

Pfeiffer syndrome is caused by mutations in the fibroblast growth factor receptors FGFR1 and FGFR2 . The syndrome is grouped into three types: type 1 (classic Pfeiffer syndrome) is milder and caused by mutations in either gene; types 2 and 3 are more severe, often leading to death in infancy, caused by mutations in FGFR2. [2]

There is no cure for the syndrome. Treatment is supportive and often involves surgery in the earliest years of life to correct skull deformities and respiratory function. [2] Most persons with Pfeiffer syndrome type 1 have a normal intelligence and life span; types 2 and 3 typically cause neurodevelopmental disorders and early death. Later in life, surgery can help in bone formation and facial construction.

Pfeiffer syndrome affects about 1 in 100,000 persons. [1] The syndrome is named after a German geneticist, Rudolf Arthur Pfeiffer (1931–2012), who described it in 1964. [3]

Signs and symptoms

Symptoms of Pfeiffer syndrome in a 17-year-old girl, 1895 Girl aged 17 years with marked proptosis Wellcome L0062481.jpg
Symptoms of Pfeiffer syndrome in a 17-year-old girl, 1895
Symptoms of Pfeiffer syndrome in a Chinese adult, 1927 Chinese circus performer with craniosynostosis, 1927.jpg
Symptoms of Pfeiffer syndrome in a Chinese adult, 1927

Many of the facial characteristics result from the premature fusion of the skull bones (craniosynostosis). The head is unable to grow normally, which leads to a high, prominent forehead (turri brachycephaly) and eyes that appear to bulge (proptosis) and are set wide (hypertelorism). In addition, there is an underdeveloped upper jaw (maxillary hypoplasia). More than half of children with Pfeiffer syndrome have hearing loss; dental problems are common. [4] A baby with Pfeiffer syndrome may have a small, beak-shaped nose; crowded, crooked teeth; and sleep apnea, due to nasal blockage. There are three main types of Pfeiffer syndrome: type I is the mildest and most common; type II is the most severe, with neurological problems and a cloverleaf deformity; and type III is similar to type II, but without the cloverleaf deformity. [5]

In people with Pfeiffer syndrome, the thumbs and first (big) toes are wide and bend away from the other digits (pollex varus and hallux varus). Unusually short fingers and toes (brachydactyly) are also common, and there may be some webbing or fusion between the digits (syndactyly). [6]

Cause

Pfeiffer syndrome is strongly associated with mutations of the fibroblast growth factor receptor 1 (FGFR1) on chromosome 8 or the fibroblast growth factor receptor 2 (FGFR2) gene on chromosome 10. [1] [7] [8] [9] These genes code for fibroblast growth factor receptors, which are important for normal bone development. [10] Advanced paternal age is thought to be a risk factor for sporadic cases of Pfeiffer syndrome due to an increase in mutations in sperm as men become older. [1] [11]

Diagnosis

Classification

The most widely accepted clinical classification of Pfeiffer syndrome was published by M. Michael Cohen in 1993. [1] [12] Cohen divided the syndrome into three possibly overlapping types, all of which are characterized by broad thumbs, broad great toes, brachydactyly and possibly syndactyly: [13]

Management

The key problem is the early fusion of the skull, which can be corrected by a series of surgical procedures, often within the first three months after birth. Later surgeries are necessary to correct respiratory and facial deformities. [2]

Outcomes

Children with Pfeiffer syndrome types 2 and 3 "have a higher risk for neurodevelopmental disorders and a reduced life expectancy" than children with Pfeiffer syndrome type 1, but if treated, favorable outcomes are possible. [14] In severe cases, respiratory and neurological complications often lead to early death.

History

The syndrome is named after German geneticist Rudolf Arthur Pfeiffer (1931–2012). [15] In 1964, Pfeiffer described eight individuals in three generations of a family who had abnormalities of the head, hands and feet (acrocephalosyndactylia) that were inherited in an autosomal dominant pattern. [1] [13] [3]

Notable cases

Related Research Articles

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<span class="mw-page-title-main">Scaphocephaly</span> Cephalic disorder involving premature fusion of the sagittal suture

Scaphocephaly, or sagittal craniosynostosis, is a type of cephalic disorder which occurs when there is a premature fusion of the sagittal suture. Premature closure results in limited lateral expansion of the skull resulting in a characteristic long, narrow head. The skull base is typically spared.

<span class="mw-page-title-main">Crouzon syndrome</span> Genetic disorder of the skull and face

Crouzon syndrome is an autosomal dominant genetic disorder known as a branchial arch syndrome. Specifically, this syndrome affects the first branchial arch, which is the precursor of the maxilla and mandible. Since the branchial arches are important developmental features in a growing embryo, disturbances in their development create lasting and widespread effects.

<span class="mw-page-title-main">Apert syndrome</span> Congenital disorder of the skull and digits

Apert syndrome is a form of acrocephalosyndactyly, a congenital disorder characterized by malformations of the skull, face, hands and feet. It is classified as a branchial arch syndrome, affecting the first branchial arch, the precursor of the maxilla and mandible. Disturbances in the development of the branchial arches in fetal development create lasting and widespread effects.

<span class="mw-page-title-main">Craniosynostosis</span> Premature fusion of bones in the skull

Craniosynostosis is a condition in which one or more of the fibrous sutures in a young infant's skull prematurely fuses by turning into bone (ossification), thereby changing the growth pattern of the skull. Because the skull cannot expand perpendicular to the fused suture, it compensates by growing more in the direction parallel to the closed sutures. Sometimes the resulting growth pattern provides the necessary space for the growing brain, but results in an abnormal head shape and abnormal facial features. In cases in which the compensation does not effectively provide enough space for the growing brain, craniosynostosis results in increased intracranial pressure leading possibly to visual impairment, sleeping impairment, eating difficulties, or an impairment of mental development combined with a significant reduction in IQ.

<span class="mw-page-title-main">Thanatophoric dysplasia</span> Severe form of genetic dwarfism that is usually lethal

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<span class="mw-page-title-main">Jackson–Weiss syndrome</span> Medical condition

Jackson–Weiss syndrome (JWS) is a genetic disorder characterized by foot abnormalities and the premature fusion of certain bones of the skull (craniosynostosis), which prevents further growth of the skull and affects the shape of the head and face. This genetic disorder can also sometimes cause intellectual disability and crossed eyes. It was characterized in 1976.

<span class="mw-page-title-main">Acrocephalosyndactyly</span> Group of diseases

Acrocephalosyndactyly is a group of autosomal dominant congenital disorders characterized by craniofacial (craniosynostosis) and hand and foot (syndactyly) abnormalities. When polydactyly is present, the classification is acrocephalopolysyndactyly. Acrocephalosyndactyly is mainly diagnosed postnatally, although prenatal diagnosis is possible if the mutation is known to be within the family genome. Treatment often involves surgery in early childhood to correct for craniosynostosis and syndactyly.

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<span class="mw-page-title-main">Muenke syndrome</span> Medical condition

Muenke syndrome, also known as FGFR3-related craniosynostosis, is a human specific condition characterized by the premature closure of certain bones of the skull during development, which affects the shape of the head and face. First described by Maximilian Muenke, the syndrome occurs in about 1 in 30,000 newborns. This condition accounts for an estimated 8 percent of all cases of craniosynostosis.

<span class="mw-page-title-main">Fibroblast growth factor receptor 2</span> Protein-coding gene in the species Homo sapiens

Fibroblast growth factor receptor 2 (FGFR2) also known as CD332 is a protein that in humans is encoded by the FGFR2 gene residing on chromosome 10. FGFR2 is a receptor for fibroblast growth factor.

<span class="mw-page-title-main">Fibroblast growth factor receptor 1</span> Protein-coding gene in the species Homo sapiens

Fibroblast growth factor receptor 1 (FGFR1), also known as basic fibroblast growth factor receptor 1, fms-related tyrosine kinase-2 / Pfeiffer syndrome, and CD331, is a receptor tyrosine kinase whose ligands are specific members of the fibroblast growth factor family. FGFR1 has been shown to be associated with Pfeiffer syndrome, and clonal eosinophilias.

<span class="mw-page-title-main">Fibroblast growth factor receptor 3</span> Gene involved in the most common form of dwarfism

Fibroblast growth factor receptor 3 is a protein that in humans is encoded by the FGFR3 gene. FGFR3 has also been designated as CD333. The gene, which is located on chromosome 4, location q16.3, is expressed in tissues such as the cartilage, brain, intestine, and kidneys.

<span class="mw-page-title-main">Frontonasal dysplasia</span> Medical condition

Frontonasal dysplasia (FND) is a congenital malformation of the midface. For the diagnosis of FND, a patient should present at least two of the following characteristics: hypertelorism, a wide nasal root, vertical midline cleft of the nose and/or upper lip, cleft of the wings of the nose, malformed nasal tip, encephalocele or V-shaped hair pattern on the forehead. The cause of FND remains unknown. FND seems to be sporadic (random) and multiple environmental factors are suggested as possible causes for the syndrome. However, in some families multiple cases of FND were reported, which suggests a genetic cause of FND.

Spider lamb syndrome, also known as spider syndrome and more formally as ovine hereditary chondrodysplasia, is a homozygous recessive disorder affecting the growth of cartilage and bone in sheep. The name derives from the limbs of afflicted animals being thin, elongated, and "spider-like".

Beare–Stevenson cutis gyrata syndrome is a rare genetic disorder characterized by craniosynostosis and a specific skin abnormality, called cutis gyrata, characterized by a furrowed and wrinkled appearance ; thick, dark, velvety areas of skin are sometimes found on the hands and feet and in the groin.

Ethylin Wang Jabs is a Chinese-American physician-scientist with expertise in medical genetics, pediatrics, and craniofacial biology. She is currently vice chair of the Department of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai Medical Center. Jabs is also a professor in the departments of developmental and regenerative biology and pediatrics at Mount Sinai and an adjunct professor in pediatrics, medicine, and surgery at the Johns Hopkins School of Medicine. Her research and clinical practice have focused on development genetics and patients with birth defects.

<span class="mw-page-title-main">Severe achondroplasia with developmental delay and acanthosis nigricans</span> Medical condition

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Holoprosencephaly-ectrodactyly-cleft lip/palate syndrome, also simply known as Hartsfield syndrome, is a rare genetic disorder characterized by the presence of variable holoprosencephaly, ectrodactyly, cleft lip and palate, alongside generalized ectodermal abnormalities. Additional findings include endocrine anomalies and developmental delays.

References

    1. 1 2 3 4 5 6 7 Vogels A, Fryns JP (2006). "Pfeiffer syndrome". Orphanet J Rare Dis. 1: 19. doi:10.1186/1750-1172-1-19. PMC   1482682 . PMID   16740155.
    2. 1 2 3 "Pfeiffer Syndrome". NORD (National Organization for Rare Disorders). Retrieved 2019-09-03.
    3. 1 2 Pfeiffer RA (1964). "Dominant erbliche Akrocephalosyndaktylie" [Dominant Hereditary Acrocephalosyndactylia]. Zeitschrift für Kinderheilkunde (in German). 90 (4): 301–20. doi:10.1007/BF00447500. PMID   14316612. S2CID   35706808.
    4. ↑ "Pfeiffer syndrome". U.S. National Library of Medicine . Retrieved 2020-10-29.
    5. ↑ "Pediatric Pfeiffer Syndrome". Children's National. Retrieved 24 February 2023.
    6. ↑ "Pfeiffer syndrome". U.S. National Library of Medicine . Retrieved 2020-10-29.
    7. ↑ Muenke M; Schell U; Hehr A; Robin NH; Losken HW; Schinzel A; et al. (1994). "A common mutation in the fibroblast growth factor receptor 1 gene in Pfeiffer syndrome". Nat Genet. 8 (3): 269–74. doi:10.1038/ng1194-269. PMID   7874169. S2CID   40033932.
    8. ↑ Rutland P; Pulleyn LJ; Reardon W; Baraitser M; Hayward R; Jones B; et al. (1995). "Identical mutations in the FGFR2 gene cause both Pfeiffer and Crouzon syndrome phenotypes". Nat Genet. 9 (2): 173–6. doi:10.1038/ng0295-173. PMID   7719345. S2CID   927144.
    9. ↑ Schell U, Hehr A, Feldman GJ, Robin NH, Zackai EH, de Die-Smulders C, et al. (1995). "Mutations in FGFR1 and FGFR2 cause familial and sporadic Pfeiffer syndrome". Hum Mol Genet. 4 (3): 323–8. doi:10.1093/hmg/4.3.323. PMID   7795583.
    10. ↑ Chan CT, Thorogood P (1999). "Pleiotropic features of syndromic craniosynostoses correlate with differential expression of fibroblast growth factor receptors 1 and 2 during human craniofacial development". Pediatr. Res. 45 (1): 46–53. doi: 10.1203/00006450-199901000-00008 . PMID   9890607.
    11. ↑ Glaser RL, Jiang W, Boyadjiev SA, Tran AK, Zachary AA, Van Maldergem L, et al. (2000). "Paternal origin of FGFR2 mutations in sporadic cases of Crouzon syndrome and Pfeiffer syndrome". Am J Hum Genet. 66 (3): 768–77. doi:10.1086/302831. PMC   1288162 . PMID   10712195.
    12. ↑ National Institutes of Health, Genetic and Rare Diseases (GARD) Information Center (2016-04-01). "Pfeiffer syndrome: Symptoms" . Retrieved 2016-05-08.
    13. 1 2 Cohen MM (1993). "Pfeiffer syndrome update, clinical subtypes, and guidelines for differential diagnosis". Am J Med Genet. 45 (3): 300–7. doi:10.1002/ajmg.1320450305. PMID   8434615.
    14. ↑ Robin NH; Scott JA; Arnold JE; Goldstein JA; Shilling BB; Marion RW; et al. (1998). "Favorable prognosis for children with Pfeiffer syndrome types 2 and 3: implications for classification". Am J Med Genet. 75 (3): 240–4. doi:10.1002/(sici)1096-8628(19980123)75:3<240::aid-ajmg2>3.3.co;2-c. PMID   9475589.
    15. ↑ synd/3477 at Who Named It?
    16. ↑ Lerner, Maura (1997-03-28). "Prince's court case touches on 2 issues: A family's right to privacy, medical ethics". Star Tribune. Minneapolis – via NewsBank.
    17. ↑ Chanen, David (1997-06-14). "Ruling: Prince's baby died from natural causes". Star Tribune. Minneapolis – via NewsBank.
    18. ↑ Pelletiere, Nicole (2016-02-02). "Mom Defends Son Against Offensive Internet Meme". ABC News . Retrieved 2016-05-08.
    19. ↑ Hernandez, Vittorio (2016-02-05). "Texas mum mad at use of photo of son with rare disorder Pfeiffer syndrome to make cruel memes". International Business Times, Australia Edition. Retrieved 2016-05-08.
    20. ↑ "Mutter wehrt sich gegen Witze, die auf Kosten ihres kranken Sohnes gemacht werden" [Mother defends against jokes that are made at the expense of her sick son]. Stern (in German). 2016-02-08. Retrieved 2016-05-08.
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