Angelman syndrome
Encyclopedia
Angelman syndrome is a neuro-genetic disorder
characterized by intellectual and developmental delay, sleep disturbance, seizures, jerky movements (especially hand-flapping), frequent laughter or smiling, and usually a happy demeanor.
AS is a classic example of genomic imprinting in that it is usually caused by deletion or inactivation of genes on the maternally inherited chromosome 15
while the paternal copy, which may be of normal sequence, is imprinted and therefore silenced. The sister syndrome, Prader-Willi syndrome
, is caused by a similar loss of paternally inherited genes and maternal imprinting. AS is named after a British pediatrician, Dr. Harry Angelman
, who first described the syndrome
in 1965. An older, alternative term for AS, happy puppet syndrome, is generally considered pejorative
and stigmatizing so it is no longer the accepted term, though it is sometimes still used as an informal term of diagnosis. People with AS are sometimes known as "angels", both because of the syndrome's name and because of their youthful, happy appearance.
, England, first reported three children with this condition in 1965. Angelman later described his choice of the title "Puppet Children" to describe these cases as being related to an oil painting he had seen while vacationing in Italy:
Case reports from the United States first began appearing in the medical literature in the early 1980s. In 1987, it was first noted that around half of the children with AS have a small piece of chromosome 15
missing (chromosome 15q partial deletion).
of about 1/20,000 and the Danish study showed a minimum AS prevalence of about 1/10,000.
Angelman syndrome is caused by the loss of the normal maternal contribution to a region of chromosome 15, most commonly by deletion of a segment of that chromosome. Other causes include uniparental disomy
, translocation
, or single gene mutation in that region. A healthy person receives two copies of chromosome 15, one from the mother, the other from the father. However, in the region of the chromosome that is critical for Angelman syndrome, the maternal and paternal contribution express certain genes very differently. This is due to gender-related epigenetic imprinting
; the biochemical mechanism is DNA methylation
. In a normal individual, the maternal allele
is expressed and the paternal allele is silenced. If the maternal contribution is lost or mutated, the result is Angelman syndrome. (When the paternal contribution is lost, by similar mechanisms, the result is Prader-Willi syndrome
.) It should be noted that the methylation test that is performed for Angelman syndrome (a defect in UBE3A) is actually looking for the gene's neighbour SNRPN (which has the opposite pattern of methylation).
Angelman syndrome can also be the result of mutation of a single gene. This gene (UBE3A
, part of the ubiquitin
pathway) is present on both the maternal and paternal chromosomes, but differs in the pattern of methylation
(imprinting). The paternal silencing of the UBE3A gene occurs in a brain region-specific manner; in the hippocampus
and cerebellum
, the maternal allele is almost exclusively the active one. The most common genetic defect leading to Angelman syndrome is an ~4Mb (mega base) maternal deletion in chromosomal region 15q11-13 causing an absence of UBE3A expression in the paternally imprinted brain regions. UBE3A codes for an E6-AP ubiquitin ligase
, which chooses its substrates very selectively, and the four identified E6-AP substrates have shed little light on the possible molecular mechanisms underlying Angelman syndrome in humans.
Initial studies of mice that do not express maternal UBE3A show severe impairments in hippocampal memory formation. Most notably, there is a deficit in a learning paradigm that involves hippocampus-dependent contextual fear conditioning
. In addition, maintenance of long-term synaptic plasticity
in hippocampal area CA1 in vitro is disrupted in Ube3a-/- mice. These results provide links amongst hippocampal synaptic plasticity
in vitro, formation of hippocampus-dependent memory in vivo, and the molecular pathology of Angelman syndrome.
Consistent (100%)
Frequent (more than 80%)
Associated (20 - 80%)
neurophysiological findings. The electroencephalogram
(EEG) in AS is usually very abnormal, and more abnormal than clinically expected. Three distinct interictal patterns are seen in these patients (see Fig.). The most common pattern is a very large amplitude 2–3 Hz rhythm most prominent in prefrontal leads (A). Next most common is a symmetrical 4–6 Hz high voltage rhythm (B). The third pattern, 3–6 Hz activity punctuated by spikes and sharp waves in occipital leads, is associated with eye closure (C). Paroxysms of laughter have no relation to the EEG, ruling out this feature as a gelastic
phenomenon (Williams 2005).
Diagnostic criteria for the disorder were initially established in 1995 in collaboration with the Angelman syndrome Foundation (USA); these criteria have undergone revision in 2005.
is important to encourage joint mobility and prevent stiffening of the joints.
Those with the syndrome are generally happy and contented people who like human contact and play. People with AS exhibit a profound desire for personal interaction with others. Communication can be difficult at first, but as a child with AS develops, there is a definite character and ability to make themselves understood. People with AS tend to develop strong non-verbal skills to compensate for their limited use of speech. It is widely accepted that their understanding of communication directed to them is much larger than their ability to return conversation. Most afflicted people will not develop more than 5–10 words, if any at all.
Seizures are a consequence, but so is excessive laughter, which is a major hindrance to early diagnosis.
gene
is thought to correlate to the least affected, whereas larger deletions on chromosome 15 are thought to correspond to the most affected.
The clinical features of Angelman syndrome alter with age. As adulthood approaches, hyperactivity and poor sleep patterns improve. The seizures decrease in frequency and often cease altogether and the EEG abnormalities are less obvious. Medication is typically advisable to those with seizure disorders. Often overlooked is the contribution of the poor sleep patterns to the frequency and/or severity of the seizures. Medication may be worthwhile in order to help deal with this issue and improve the prognosis with respect to seizures and sleep. Also noteworthy are the reports that the frequency and severity of seizures temporarily escalate in pubescent Angelman syndrome girls but do not seem to affect long-term health.
The facial features remain recognizable but many adults with AS look remarkably youthful for their age.
Puberty
and menstruation
begin at around the average age. Sexual development is thought to be unaffected, as evidenced by a single reported case of a woman with Angelman syndrome conceiving a female child who also had Angelman syndrome.
The majority of those with AS achieve continence
by day and some by night. Angelman syndrome is not a degenerative syndrome. Many people with AS improve their living skills with support.
Dressing skills are variable and usually limited to items of clothing without buttons or zippers. Most adults are able to eat with a knife or spoon and fork and can learn to perform simple household tasks. General health is fairly good and life-span near average. Particular problems which have arisen in adults are a tendency to obesity (more in females), and worsening of scoliosis
if it is present. The affectionate nature which is also a positive aspect in the younger children may also persist into adult life where it can pose a problem socially, but this problem is not insurmountable.
, author Ian Rankin
, professional baseball player Dave Henderson
, and professional hockey player Peter McDuffe
have sons with AS.
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
characterized by intellectual and developmental delay, sleep disturbance, seizures, jerky movements (especially hand-flapping), frequent laughter or smiling, and usually a happy demeanor.
AS is a classic example of genomic imprinting in that it is usually caused by deletion or inactivation of genes on the maternally inherited chromosome 15
Chromosome 15 (human)
right|frame|Human chromosome 15Chromosome 15 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 15 spans about 106 million base pairs and represents between 3% and 3.5% of the total DNA in cells.Identifying genes on each chromosome is an...
while the paternal copy, which may be of normal sequence, is imprinted and therefore silenced. The sister syndrome, Prader-Willi syndrome
Prader-Willi syndrome
Prader–Willi syndrome is a rare genetic disorder in which seven genes on chromosome 15 are deleted or unexpressed on the paternal chromosome...
, is caused by a similar loss of paternally inherited genes and maternal imprinting. AS is named after a British pediatrician, Dr. Harry Angelman
Harry Angelman
Harry Angelman was a British consultant paediatrician who identified Angelman Syndrome.-Biography:Angelman was born in Birkenhead in 1915 and qualified in Liverpool. Angelman was an enthusiast for the language and country of Italy. He had observed three children who were unrelated but showed...
, who first described the syndrome
Syndrome
In medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others...
in 1965. An older, alternative term for AS, happy puppet syndrome, is generally considered pejorative
Pejorative
Pejoratives , including name slurs, are words or grammatical forms that connote negativity and express contempt or distaste. A term can be regarded as pejorative in some social groups but not in others, e.g., hacker is a term used for computer criminals as well as quick and clever computer experts...
and stigmatizing so it is no longer the accepted term, though it is sometimes still used as an informal term of diagnosis. People with AS are sometimes known as "angels", both because of the syndrome's name and because of their youthful, happy appearance.
History
Dr. Harry Angelman, a pediatrician working in WarringtonWarrington
Warrington is a town, borough and unitary authority area of Cheshire, England. It stands on the banks of the River Mersey, which is tidal to the west of the weir at Howley. It lies 16 miles east of Liverpool, 19 miles west of Manchester and 8 miles south of St Helens...
, England, first reported three children with this condition in 1965. Angelman later described his choice of the title "Puppet Children" to describe these cases as being related to an oil painting he had seen while vacationing in Italy:
Case reports from the United States first began appearing in the medical literature in the early 1980s. In 1987, it was first noted that around half of the children with AS have a small piece of chromosome 15
Chromosome 15 (human)
right|frame|Human chromosome 15Chromosome 15 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 15 spans about 106 million base pairs and represents between 3% and 3.5% of the total DNA in cells.Identifying genes on each chromosome is an...
missing (chromosome 15q partial deletion).
Prevalence
Though the prevalence of Angelman syndrome is not precisely known, there are some estimates. The best data available are from studies of school age children, ages 6–13 years, living in Sweden and from Denmark where the diagnosis of AS children in medical clinics was compared to an 8 year period of about 45,000 births. The Swedish study showed an AS prevalencePrevalence
In epidemiology, the prevalence of a health-related state in a statistical population is defined as the total number of cases of the risk factor in the population at a given time, or the total number of cases in the population, divided by the number of individuals in the population...
of about 1/20,000 and the Danish study showed a minimum AS prevalence of about 1/10,000.
Pathophysiology
Uniparental disomy
Uniparental disomy occurs when a person receives two copies of a chromosome, or part of a chromosome, from one parent and no copies from the other parent.. UPD could involve isodisomy or heterodisomy ....
, translocation
Chromosomal translocation
In genetics, a chromosome translocation is a chromosome abnormality caused by rearrangement of parts between nonhomologous chromosomes. A gene fusion may be created when the translocation joins two otherwise separated genes, the occurrence of which is common in cancer. It is detected on...
, or single gene mutation in that region. A healthy person receives two copies of chromosome 15, one from the mother, the other from the father. However, in the region of the chromosome that is critical for Angelman syndrome, the maternal and paternal contribution express certain genes very differently. This is due to gender-related epigenetic imprinting
Imprinting (genetics)
Genomic imprinting is a genetic phenomenon by which certain genes are expressed in a parent-of-origin-specific manner. It is an inheritance process independent of the classical Mendelian inheritance. Imprinted alleles are silenced such that the genes are either expressed only from the non-imprinted...
; the biochemical mechanism is DNA methylation
DNA methylation
DNA methylation is a biochemical process that is important for normal development in higher organisms. It involves the addition of a methyl group to the 5 position of the cytosine pyrimidine ring or the number 6 nitrogen of the adenine purine ring...
. In a normal individual, the maternal allele
Allele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...
is expressed and the paternal allele is silenced. If the maternal contribution is lost or mutated, the result is Angelman syndrome. (When the paternal contribution is lost, by similar mechanisms, the result is Prader-Willi syndrome
Prader-Willi syndrome
Prader–Willi syndrome is a rare genetic disorder in which seven genes on chromosome 15 are deleted or unexpressed on the paternal chromosome...
.) It should be noted that the methylation test that is performed for Angelman syndrome (a defect in UBE3A) is actually looking for the gene's neighbour SNRPN (which has the opposite pattern of methylation).
Angelman syndrome can also be the result of mutation of a single gene. This gene (UBE3A
UBE3A
Ubiquitin-protein ligase E3A also known as E6AP ubiquitin-protein ligase is an enzyme that in humans is encoded by the UBE3A gene. This enzyme is involved in targeting proteins for degradation within cells...
, part of the ubiquitin
Ubiquitin
Ubiquitin is a small regulatory protein that has been found in almost all tissues of eukaryotic organisms. Among other functions, it directs protein recycling.Ubiquitin can be attached to proteins and label them for destruction...
pathway) is present on both the maternal and paternal chromosomes, but differs in the pattern of methylation
Methylation
In the chemical sciences, methylation denotes the addition of a methyl group to a substrate or the substitution of an atom or group by a methyl group. Methylation is a form of alkylation with, to be specific, a methyl group, rather than a larger carbon chain, replacing a hydrogen atom...
(imprinting). The paternal silencing of the UBE3A gene occurs in a brain region-specific manner; in the hippocampus
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...
and cerebellum
Cerebellum
The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...
, the maternal allele is almost exclusively the active one. The most common genetic defect leading to Angelman syndrome is an ~4Mb (mega base) maternal deletion in chromosomal region 15q11-13 causing an absence of UBE3A expression in the paternally imprinted brain regions. UBE3A codes for an E6-AP ubiquitin ligase
Ubiquitin ligase
A ubiquitin ligase is a protein that in combination with an E2 ubiquitin-conjugating enzyme causes the attachment of ubiquitin to a lysine on a target protein via an isopeptide bond; the E3 ubiquitin ligase targets specific protein substrates for degradation by the proteasome...
, which chooses its substrates very selectively, and the four identified E6-AP substrates have shed little light on the possible molecular mechanisms underlying Angelman syndrome in humans.
Initial studies of mice that do not express maternal UBE3A show severe impairments in hippocampal memory formation. Most notably, there is a deficit in a learning paradigm that involves hippocampus-dependent contextual fear conditioning
Fear conditioning
Fear conditioning is a behavioral paradigm in which organisms learn to predict aversive events. It is a form of learning in which an aversive stimulus is associated with a particular neutral context or neutral stimulus , resulting in the expression of fear responses to the originally neutral...
. In addition, maintenance of long-term synaptic plasticity
Synaptic plasticity
In neuroscience, synaptic plasticity is the ability of the connection, or synapse, between two neurons to change in strength in response to either use or disuse of transmission over synaptic pathways. Plastic change also results from the alteration of the number of receptors located on a synapse...
in hippocampal area CA1 in vitro is disrupted in Ube3a-/- mice. These results provide links amongst hippocampal synaptic plasticity
Synaptic plasticity
In neuroscience, synaptic plasticity is the ability of the connection, or synapse, between two neurons to change in strength in response to either use or disuse of transmission over synaptic pathways. Plastic change also results from the alteration of the number of receptors located on a synapse...
in vitro, formation of hippocampus-dependent memory in vivo, and the molecular pathology of Angelman syndrome.
Clinical features
The following list features of Angelman syndrome and their relative frequency in affected individuals.Consistent (100%)
- Developmental delay, functionally severe
- Speech impairment, no or minimal use of words; receptive and non-verbal communication skills higher than verbal ones
- Movement or balance disorder, usually ataxiaAtaxiaAtaxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
of gait and/or tremulous movement of limbs - Behavioral uniqueness: any combination of frequent laughter/smiling; apparent happy demeanor; easily excitable personality, often with hand flapping movements; hypermotoric behavior; short attention span
Frequent (more than 80%)
- Delayed, disproportionate growth in head circumference, usually resulting in microcephalyMicrocephalyMicrocephaly is a neurodevelopmental disorder in which the circumference of the head is more than two standard deviations smaller than average for the person's age and sex. Microcephaly may be congenital or it may develop in the first few years of life...
(absolute or relative) by age 2 - Seizures, onset usually < 3 years of age
- Abnormal EEG, characteristic pattern with large amplitude slow-spike waves
Associated (20 - 80%)
- StrabismusStrabismusStrabismus is a condition in which the eyes are not properly aligned with each other. It typically involves a lack of coordination between the extraocular muscles, which prevents bringing the gaze of each eye to the same point in space and preventing proper binocular vision, which may adversely...
- Hypopigmented skin and eyes
- Tongue thrusting; suck/swallowing disorders
- Hyperactive tendon reflexes
- Feeding problems during infancy
- Uplifted, flexed arms during walking
- Prominent mandible
- Increased sensitivity to heat
- Wide mouth, wide-spaced teeth
- Sleep disturbance
- Frequent drooling, protruding tongue
- Attraction to/fascination with water
- Excessive chewing/mouthing behaviors
- Flat back of head
- Smooth palms
Neurophysiology
One of the more notable features of Angelman Syndrome (AS) is the syndrome’s pathognomonicPathognomonic
Pathognomonic is a term, often used in medicine, that means characteristic for a particular disease. A pathognomonic sign is a particular sign whose presence means that a particular disease is present beyond any doubt...
neurophysiological findings. The electroencephalogram
Electroencephalography
Electroencephalography is the recording of electrical activity along the scalp. EEG measures voltage fluctuations resulting from ionic current flows within the neurons of the brain...
(EEG) in AS is usually very abnormal, and more abnormal than clinically expected. Three distinct interictal patterns are seen in these patients (see Fig.). The most common pattern is a very large amplitude 2–3 Hz rhythm most prominent in prefrontal leads (A). Next most common is a symmetrical 4–6 Hz high voltage rhythm (B). The third pattern, 3–6 Hz activity punctuated by spikes and sharp waves in occipital leads, is associated with eye closure (C). Paroxysms of laughter have no relation to the EEG, ruling out this feature as a gelastic
Gelastic seizure
A gelastic seizure, also known as "gelastic epilepsy" is a rare type of seizure that involves a sudden burst of energy, usually in the form of laughing or crying. This syndrome usually occurs for no obvious reason and is uncontrollable. It is slightly more common in males than females. The term...
phenomenon (Williams 2005).
Diagnosis
The diagnosis of Angelman syndrome is based on:- A history of delayed motor milestones and then later a delay in general development, especially of speech
- Unusual movements including fine tremors, jerky limb movements, hand flapping and a wide-based, stiff-legged gait.
- Characteristic facial appearance (but not in all cases).
- A history of epilepsy and an abnormal EEGElectroencephalographyElectroencephalography is the recording of electrical activity along the scalp. EEG measures voltage fluctuations resulting from ionic current flows within the neurons of the brain...
tracing. - A happy disposition with frequent laughter
- A deletion or inactivity on chromosome 15 by array comparative genomic hybridization (aCGH) or by BACs-on-Beads technology.
Diagnostic criteria for the disorder were initially established in 1995 in collaboration with the Angelman syndrome Foundation (USA); these criteria have undergone revision in 2005.
Treatment and care
There is currently no cure available. The epilepsy can be controlled by the use of one or more types of anticonvulsant medications. However, there are difficulties in ascertaining the levels and types of anticonvulsant medications needed to establish control, because AS is usually associated with having multiple varieties of seizures, rather than just the one as in normal cases of epilepsy. Many families use melatonin to promote sleep in a condition which often affects sleep patterns. Many individuals with Angelman syndrome sleep for a maximum of 5 hours at any one time. Mild laxatives are also used frequently to encourage regular bowel movements and early intervention with physiotherapyPhysical therapy
Physical therapy , often abbreviated PT, is a health care profession. Physical therapy is concerned with identifying and maximizing quality of life and movement potential within the spheres of promotion, prevention, diagnosis, treatment/intervention,and rehabilitation...
is important to encourage joint mobility and prevent stiffening of the joints.
Those with the syndrome are generally happy and contented people who like human contact and play. People with AS exhibit a profound desire for personal interaction with others. Communication can be difficult at first, but as a child with AS develops, there is a definite character and ability to make themselves understood. People with AS tend to develop strong non-verbal skills to compensate for their limited use of speech. It is widely accepted that their understanding of communication directed to them is much larger than their ability to return conversation. Most afflicted people will not develop more than 5–10 words, if any at all.
Seizures are a consequence, but so is excessive laughter, which is a major hindrance to early diagnosis.
Prognosis
The severity of the symptoms associated with Angelman syndrome varies significantly across the population of those affected. Some speech and a greater degree of self-care are possible among the least profoundly affected. Unfortunately, walking and the use of simple sign language may be beyond the reach of the more profoundly affected. Early and continued participation in physical, occupational (related to the development of fine-motor control skills), and communication (speech) therapies are believed to improve significantly the prognosis (in the areas of cognition and communication) of individuals affected by AS. Further, the specific genetic mechanism underlying the condition is thought to correlate to the general prognosis of the affected person. On one end of the spectrum, a mutation to the UBE3AUBE3A
Ubiquitin-protein ligase E3A also known as E6AP ubiquitin-protein ligase is an enzyme that in humans is encoded by the UBE3A gene. This enzyme is involved in targeting proteins for degradation within cells...
gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
is thought to correlate to the least affected, whereas larger deletions on chromosome 15 are thought to correspond to the most affected.
The clinical features of Angelman syndrome alter with age. As adulthood approaches, hyperactivity and poor sleep patterns improve. The seizures decrease in frequency and often cease altogether and the EEG abnormalities are less obvious. Medication is typically advisable to those with seizure disorders. Often overlooked is the contribution of the poor sleep patterns to the frequency and/or severity of the seizures. Medication may be worthwhile in order to help deal with this issue and improve the prognosis with respect to seizures and sleep. Also noteworthy are the reports that the frequency and severity of seizures temporarily escalate in pubescent Angelman syndrome girls but do not seem to affect long-term health.
The facial features remain recognizable but many adults with AS look remarkably youthful for their age.
Puberty
Puberty
Puberty is the process of physical changes by which a child's body matures into an adult body capable of reproduction, as initiated by hormonal signals from the brain to the gonads; the ovaries in a girl, the testes in a boy...
and menstruation
Menstruation
Menstruation is the shedding of the uterine lining . It occurs on a regular basis in sexually reproductive-age females of certain mammal species. This article focuses on human menstruation.-Overview:...
begin at around the average age. Sexual development is thought to be unaffected, as evidenced by a single reported case of a woman with Angelman syndrome conceiving a female child who also had Angelman syndrome.
The majority of those with AS achieve continence
Urinary incontinence
Urinary incontinence is any involuntary leakage of urine. It is a common and distressing problem, which may have a profound impact on quality of life. Urinary incontinence almost always results from an underlying treatable medical condition but is under-reported to medical practitioners...
by day and some by night. Angelman syndrome is not a degenerative syndrome. Many people with AS improve their living skills with support.
Dressing skills are variable and usually limited to items of clothing without buttons or zippers. Most adults are able to eat with a knife or spoon and fork and can learn to perform simple household tasks. General health is fairly good and life-span near average. Particular problems which have arisen in adults are a tendency to obesity (more in females), and worsening of scoliosis
Scoliosis
Scoliosis is a medical condition in which a person's spine is curved from side to side. Although it is a complex three-dimensional deformity, on an X-ray, viewed from the rear, the spine of an individual with scoliosis may look more like an "S" or a "C" than a straight line...
if it is present. The affectionate nature which is also a positive aspect in the younger children may also persist into adult life where it can pose a problem socially, but this problem is not insurmountable.
Notable cases
Actor Colin FarrellColin Farrell
Colin James Farrell is an Irish actor, who has appeared in such film as Tigerland, Miami Vice, Minority Report, Phone Booth, The Recruit, Alexander and S.W.A.T....
, author Ian Rankin
Ian Rankin
Ian Rankin, OBE, DL , is a Scottish crime writer. His best known books are the Inspector Rebus novels. He has also written several pieces of literary criticism.-Background:He attended Beath High School, Cowdenbeath...
, professional baseball player Dave Henderson
Dave Henderson
David Lee Henderson , nicknamed Hendu, is an American former Major League Baseball player who played for the Seattle Mariners , Boston Red Sox , San Francisco Giants , Oakland Athletics and Kansas City Royals . He batted and threw right-handed...
, and professional hockey player Peter McDuffe
Peter McDuffe
Peter Arnold "Pete" McDuffe was a Canadian professional ice hockey goaltender who played for the St. Louis Blues, New York Rangers, Kansas City Scouts and Detroit Red Wings in the National Hockey League and the Indianapolis Racers in the World Hockey AssociationMcDuffe won the 1970–71 CHL Most...
have sons with AS.