Pfeiffer syndrome is a rare
genetic disorder
A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...
characterized by the premature fusion of certain bones of the
skull
The skull is a bone protective cavity for the brain. The skull is composed of four types of bone i.e., cranial bones, facial bones, ear ossicles and hyoid bone. However two parts are more prominent: the cranium and the mandible. In humans, the ...
(
craniosynostosis
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 perpe ...
) which affects the shape of the head and face. In addition, the syndrome includes abnormalities of the hands (such as wide and deviated thumbs) and feet (such as wide and deviated big toes).
Pfeiffer syndrome is caused by mutations in the
fibroblast growth factor receptors
A fibroblast is a type of cell (biology), biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework (Stroma (tissue), stroma) for animal Tissue (biology), tissues, and plays a critical role in wound ...
''
FGFR1
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 ...
'' and ''
FGFR2
Fibroblast growth factor receptor 2 (FGFR2) also known as CD332 (cluster of differentiation 332) is a protein that in humans is encoded by the ''FGFR2'' gene residing on chromosome 10. FGFR2 is a receptor for fibroblast growth factor.
The protein ...
''. The syndrome is grouped into three types, type 1 (classic Pfeiffer syndrome) being milder and caused by mutations in either gene and types 2 and 3 being more severe, often leading to death in infancy, caused by mutations in ''FGFR2''.
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.
Most individuals with Pfeiffer syndrome type 1 have a normal intelligence and life span, while types 2 and 3 typically result in
neurodevelopmental disorders
Neurodevelopmental disorders are a group of disorders that affect the development of the nervous system, leading to abnormal brain function which may affect emotion, learning ability, self-control, and memory. The effects of neurodevelopmental ...
and early death.
Pfeiffer syndrome affects about 1 in 100,000 births.
The syndrome is named after German geneticist
Rudolf Arthur Pfeiffer
Rudolf Arthur Pfeiffer (30 March 1931 – 1 June 2012) was a German geneticist. He discovered Pfeiffer syndrome in 1964.
Pfeiffer was born in Saarbrücken, Germany, on 30 March 1931.
He studied at the Universities of University of Vienna, Vienna, ...
(1931–2012), who described it in 1964.
Signs and symptoms
![Chinese circus performer with craniosynostosis, 1927](https://upload.wikimedia.org/wikipedia/commons/d/dc/Chinese_circus_performer_with_craniosynostosis%2C_1927.jpg)
Many of the characteristic facial features result from the premature fusion of the skull bones (
craniosynostosis
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 perpe ...
). The head is unable to grow normally, which leads to a high prominent forehead (
turribrachycephaly
Brachycephaly (derived from the Ancient Greek '' βραχύς'', 'short' and '' κεφαλή'', 'head') is the shape of a skull shorter than typical for its species. It is perceived as a desirable trait in some domesticated dog and cat breeds, ...
), and eyes that appear to bulge (
proptosis
Exophthalmos (also called exophthalmus, exophthalmia, proptosis, or exorbitism) is a bulging of the eye anteriorly out of the orbit. Exophthalmos can be either bilateral (as is often seen in Graves' disease) or unilateral (as is often seen in ...
) and are wide-set (
hypertelorism
Hypertelorism is an abnormally increased distance between two organs or bodily parts, usually referring to an increased distance between the orbits (eyes), or orbital hypertelorism. In this condition the distance between the inner eye corners as ...
). In addition, there is an underdeveloped upper jaw (
maxillary hypoplasia
Maxillary hypoplasia, or maxillary deficiency, is an underdevelopment of the maxillary bone, bones of the upper jaw. It is associated with Crouzon syndrome, Angelman syndrome, as well as Fetal alcohol syndrome. It can also be associated with Cleft ...
). More than 50 percent of children with Pfeiffer syndrome have hearing loss; dental problems are also common.
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
Brachydactyly (Greek βραχύς = "short" plus δάκτυλος = "finger"), is a medical term which literally means "short finger". The shortness is relative to the length of other long bones and other parts of the body. Brachydactyly is an in ...
) are also common, and there may be some webbing or fusion between the digits (
syndactyly
Syndactyly is a condition wherein two or more digits are fused together. It occurs normally in some mammals, such as the siamang and diprotodontia, but is an unusual condition in humans. The term is from Greek σύν, ''syn'' 'together' and δάκ ...
).
Cause
Pfeiffer syndrome is strongly associated with mutations of the
fibroblast growth factor receptor 1
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 ...
(''FGFR1'') on
chromosome 8
Chromosome 8 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 8 spans about 145 million base pairs (the building material of DNA) and represents between 4.5 and 5.0% of the total DNA ...
or the
fibroblast growth factor receptor 2
Fibroblast growth factor receptor 2 (FGFR2) also known as CD332 (cluster of differentiation 332) is a protein that in humans is encoded by the ''FGFR2'' gene residing on chromosome 10. FGFR2 is a receptor for fibroblast growth factor.
The protein ...
(''FGFR2'') gene on
chromosome 10
Chromosome 10 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 10 spans about 133 million base pairs (the building material of DNA) and represents between 4 and 4.5 percent of the tota ...
.
These genes code for fibroblast growth factor receptor
A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells of ...
s, which are important for normal bone development. 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.
Diagnosis
Classification
The most widely accepted clinical classification of Pfeiffer syndrome was published by M. Michael Cohen in 1993.[ Cohen divided the syndrome into three possibly overlapping types, all of which are characterized by broad thumbs, broad great toes, ]brachydactyly
Brachydactyly (Greek βραχύς = "short" plus δάκτυλος = "finger"), is a medical term which literally means "short finger". The shortness is relative to the length of other long bones and other parts of the body. Brachydactyly is an in ...
and possibly syndactyly
Syndactyly is a condition wherein two or more digits are fused together. It occurs normally in some mammals, such as the siamang and diprotodontia, but is an unusual condition in humans. The term is from Greek σύν, ''syn'' 'together' and δάκ ...
:
* Type 1, also known as classic Pfeiffer syndrome, includes craniosynostosis and "midface deficiency". This type is inherited in an autosomal dominant
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
pattern. Most individuals with type 1 Pfeiffer syndrome have normal intelligence and a normal life span.
* Type 2 includes a cloverleaf-shaped skull, due to extensive fusion of bones, as well as severe proptosis
Exophthalmos (also called exophthalmus, exophthalmia, proptosis, or exorbitism) is a bulging of the eye anteriorly out of the orbit. Exophthalmos can be either bilateral (as is often seen in Graves' disease) or unilateral (as is often seen in ...
. This type occurs sporadically (i.e., does not appear to be inherited) and has "a poor prognosis and severe neurological compromise, generally with early death".
* Type 3 includes craniosynostosis and severe proptosis. This type occurs sporadically (i.e., does not appear to be inherited) and has "a poor prognosis and severe neurological compromise, generally with early death."
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.
Outcomes
Children with Pfeiffer syndrome types 2 and 3 "have a higher risk for neurodevelopmental disorders
Neurodevelopmental disorders are a group of disorders that affect the development of the nervous system, leading to abnormal brain function which may affect emotion, learning ability, self-control, and memory. The effects of neurodevelopmental ...
and a reduced life expectancy" than children with Pfeiffer syndrome type 1, but if treated, favorable outcomes are possible. In severe cases, respiratory and neurological complications often lead to early death.
History
The syndrome is named after German geneticist Rudolf Arthur Pfeiffer
Rudolf Arthur Pfeiffer (30 March 1931 – 1 June 2012) was a German geneticist. He discovered Pfeiffer syndrome in 1964.
Pfeiffer was born in Saarbrücken, Germany, on 30 March 1931.
He studied at the Universities of University of Vienna, Vienna, ...
(1931–2012). 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
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
pattern.
Notable cases
* In 1996, a son was born to American musician Prince
A prince is a male ruler (ranked below a king, grand prince, and grand duke) or a male member of a monarch's or former monarch's family. ''Prince'' is also a title of nobility (often highest), often hereditary, in some European states. Th ...
and his wife Mayte Garcia
Mayte Jannell Garcia (; born November 12, 1973) is an American dancer, actress and singer. She was married to Prince for four years and has worked with various music artists.
Early life
Garcia was born on November 12, 1973, at Fort Rucker, Ala ...
. The highly anticipated child, Amiir ("prince" in Arabic), was diagnosed at birth with Pfeiffer syndrome type 2 and died several days later. In 1997, after Garcia's former personal assistants raised concerns about the manner of death, the medical examiner performed an investigation and declared that the death was due to natural causes (meaning it was not a homicide).
* In 2014, the mother of a boy in Texas with Pfeiffer syndrome type 1 posted a photograph of the child to her blog. In 2016, she discovered that the photograph had been used in a meme
A meme ( ) is an idea, behavior, or style that spreads by means of imitation from person to person within a culture and often carries symbolic meaning representing a particular phenomenon or theme. A meme acts as a unit for carrying cultural i ...
comparing her son to a pug
The Pug is a breed of dog originally from China, with physically distinctive features of a wrinkly, short-muzzled face and curled tail. The breed has a fine, glossy coat that comes in a variety of colors, most often light brown (fawn) or blac ...
. Her efforts to remove the meme from the Internet, especially social media such as Instagram
Instagram is a photo and video sharing social networking service owned by American company Meta Platforms. The app allows users to upload media that can be edited with filters and organized by hashtags and geographical tagging. Posts can ...
, Twitter
Twitter is an online social media and social networking service owned and operated by American company Twitter, Inc., on which users post and interact with 280-character-long messages known as "tweets". Registered users can post, like, and ...
, and Facebook
Facebook is an online social media and social networking service owned by American company Meta Platforms. Founded in 2004 by Mark Zuckerberg with fellow Harvard College students and roommates Eduardo Saverin, Andrew McCollum, Dustin M ...
, attracted international attention.
References
External links
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{{Receptor deficiencies
Cell surface receptor deficiencies
Congenital disorders
Rare syndromes
Hearing loss with craniofacial syndromes
Syndromes with dysmelia