Aarskog syndrome
Named after Norwegian paediatrian and human geneticist, born December 10, 1928, Ålesund who first described a Norwegian family in 1970,
Synonyms: Aarskog-Scott syndrome; Greig syndrome; facial-digital-genital syndrome; facio-digito-genital syndrome; facio-digito-genital syndrome; shawl scrotum syndrome.
Hereditary/Genetic: Transmitted as an X-linked trait. Napped to the short arm of chromosome X (Xp11.22). Almost exclusively male.
Prevelance: unknown
Clinical Features:
Head and neck: A round face, broad forehead, hypoplastic ridging of the metopic sutures, and maxilla with relative mandibular prognathism are the main characteristics.
Ears: Thickeners and fleshiness of the earlobes.
Mouth and oral structures: A curved depression below the lover lip may be associated.
Abdomen: Prominent umbilicus is frequent.
Hand and foot: Tissue webbing between fingers and joint hypermobility with a pronounced hyperextension and flexion of the interphalangeal joints. Some patients exhibit fifth finger clinodactyly. The feet are flat, broad, and small with bulbous toes. Metatarsal abduction occurs in about half of all cases. Dermatoglyphic findings consist of single palmar creases. Also may include Simian crease,
Extremities: Joint hyperlaxity.
Spine: Spina bifida occulta, cervical vertebral defects, hypoplasia of the first cervical vertebra with unfused posterior arch, and subluxation of the first and second cervical vertebrae,
Skin appendages: Widow's peak.
Urogenital system: Shawl scrotum.
Growth and development: Growth retardation. 30% of the affected males are mentally retarded.
Behavior and performance: Hyperactivity and attention deficit are frequent.
Lymphatic dysplasia: lymphedema
Complications:
Cystic changes in the brainDifficulty growing in the first year of life
Poorly aligned teeth
Siezures
Undescended testicle
Treatment:
There is no "treatment" for the main condition. Treatment would focus on the clinical features and complications.
May 26, 2008
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Clinical and General Information:
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Aarskog syndrome
Definition
Aarskog syndrome is an inherited disease characterized by short stature, facial abnormalities, musculoskeletal, and genital anomalies.Causes, incidence, and risk factors
Aarskog syndrome is an x-linked recessive genetic disorder. This disorder affects mainly males, although females may have a milder manifestation of some of the features. It is caused by mutations in a gene called FGDY1 found on the X chromosome.Symptoms
Signs and tests
X-rays will reveal skeletal abnormalities. Genetic testing may be available for mutations in the FGDY1 gene.Treatment
Orthodontic treatment may be attempted for some of the facial abnormalities. Trials of growth hormone have not been effective to treat short stature in this disorder.Support Groups
The MAGIC Foundation for Children's Growth is a support group for Aarskog syndrome and can be found at www.magicfoundation.org.
Expectations (prognosis)
Mild degrees of mental slowness may be present, but affected children usually have good social skills. Some males may exhibit reduced fertility.Complications
Some recent findings have included cystic changes in the brain and generalized seizures. There may be difficulty growing in the first year of life in up to one-third of cases. Misaligned teeth may require orthodontic correction. An undescended testicle will require surgery.Calling your health care provider
Call your health care provider if your child exhibits delays in growth or if you notice any of the irregularities described here. Seek genetic counseling if there is Aarskog syndrome in your family. Seek evaluation by a geneticist if your doctor thinks you or your child may have Aarskog syndrome.Prevention
There is no guaranteed prevention. Prenatal testing may be available in cases where a relative has a known mutation.Update Date: 1/30/2004
Updated by: Douglas R. Stewart, M.D., Division of Medical Genetics, Hospital of the University of Pennsylvania, Philadelphia, PA. Review provided by VeriMed Healthcare Network.
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Aarskog syndrome
Synonyms of Aarskog Syndrome
Disorder Subdivisions
General Discussion
Aarskog syndrome is an extremely rare genetic disorder marked by
stunted growth
that may not become obvious until the child is about three years of
age, broad
facial abnormalities, musculoskeletal and genital anomalies, and mild
mental
retardation.
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Abstracts and Studies:
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Unilateral focal polymicrogyria in a patient with classical Aarskog-Scott syndrome due to a novel missense mutation in an evolutionary conserved RhoGEF domain of the faciogenital dysplasia gene FGD1
Am J Med Genet A. 2007 Oct
Division of Medical Genetics, Geneva University Hospitals, Geneva, Switzerland.
Faciogenital dysplasia or Aarskog-Scott syndrome (AAS) is an X-linked disorder characterized by craniofacial, skeletal, and urogenital malformations and short stature. Mutations in the only known causative gene FGD1 are found in about one-fifth of the cases with the clinical diagnosis of AAS. FGD1 is a guanine nucleotide exchange factor (GEF) that specifically activates the Rho GTPase Cdc42 via its RhoGEF domain. The Cdc42 pathway is involved in skeletal formation and multiple aspects of neuronal development. We describe a boy with typical AAS and, in addition, unilateral focal polymicrogyria (PMG), a feature hitherto unreported in AAS. Sequencing of the FGD1 gene in the index case and his mother revealed the presence of a novel mutation (1396A>G; M466V), located in the evolutionary conserved alpha-helix 4 of the RhoGEF domain. M466V was not found in healthy family members, in >300 healthy controls and AAS patients, and has not been reported in the literature or mutation databases to date, indicating that this novel missense mutation causes AAS, and possibly PMG. Brain cortex malformations such as PMG could be initiated by mutations in the evolutionary conserved RhoGEF domain of FGD1, by perturbing the signaling via Rho GTPases such as Cdc42 known to cause brain malformation.
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A newly recognized craniosynostosis syndrome with features of Aarskog-Scott and Teebi syndromes.
Am J Med Genet A. 2007 Jun
Division of Genetics, Department of Pediatrics, Tufts-New England Medical Center, Boston, Massachusetts 02111, USA. jhoffman@tufts-nemc.org
We present two unrelated boys with craniosynostosis and similar facial features including hypertelorism, down-slanted palpebral fissures, ptosis, broad mouth with a thin upper lip, and preauricular pits. Both patients had short, broad first digits as well as short, broad hands. Both also had respiratory difficulties and umbilical abnormalities. Although, many of these features are seen in Aarskog-Scott and in Teebi hypertelorism syndromes, both children had craniosynostosis, which has not been previously reported in either syndrome. We propose that these children may have a previously unreported syndrome consistent with X-linked inheritance, although an autosomal dominant mode of transmission cannot be excluded.
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Aarskog syndrome with aortic root dilatation and sub-valvular aortic stenosis: surgical management.
Interact Cardiovasc Thorac Surg. 2005 Feb
Regional Cardiothoracic Centre, Freeman Hospital, Newcastle upon Tyne, NE7 7DN, UK.
Aarskog syndrome is a familial condition associated with craniofacial anomalies, genital malformations and short stature. Affected children have significantly higher chance of having congenital heart disease (CHD) than the general population. We report the case of a child afflicted with progressive aortic root dilatation and sub-valvular aortic stenosis, successfully managed with aortic root and valve replacement. Given the association between Aarskog syndrome and CHD, cardiac surveillance should be undertaken in all affected children.
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| GeneTests, Links | |
| AARSKOG SYNDROME | |
Grier et al. (1983) reported father and 2 sons with typical Aarskog syndrome, including short stature, hypertelorism, and shawl scrotum. They tabulated the findings in 82 previous cases. X-linked recessive inheritance has been repeatedly suggested (see 305400). The family reported by Welch (1974) had affected males in 3 consecutive generations. Thus, there is either genetic heterogeneity or this is an autosomal dominant with strong sex-influence and possibly ascertainment bias resulting from use of the shawl scrotum as a main criterion. Stretchable skin was present in the cases of Grier et al. (1983). Teebi et al. (1993) reported the case of an affected mother and 4 sons (including a pair of monozygotic twins) by 2 different husbands. They suggested that the manifestations were as severe in the mother as in the sons and that this suggested autosomal dominant inheritance. Actually, the mother seemed less severely affected, compatible with X-linked inheritance.
Victor A. McKusick : 6/4/1986
alopez :
6/3/1997
mimadm : 3/11/1994
carol : 7/7/1993
supermim : 3/16/1992
supermim : 3/20/1990
ddp : 10/26/1989
marie : 3/25/1988
Copyright © 1966-2004 Johns Hopkins University
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=100050
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| FACIOGENITAL DYSPLASIA |
Alternative titles; symbols
FGDYAarskog
(1970) described an X-linked disorder characterized by ocular
hypertelorism,
anteverted nostrils, broad upper lip, and peculiar penoscrotal
relations
('saddle-bag scrotum' or 'shawl scrotum'). Affected males can
reproduce. Scott
(1971) emphasized the occurrence of ligamentous laxity
manifest by
hyperextensibility of the fingers, genu recurvatum, and flat feet.
Furthermore,
hypermobility in the cervical spine with anomaly of the odontoid
resulted in
neurologic deficit. He studied a family with 9 affected males in 5
sibships. Sugarman
et al. (1973) described a kindred with 4 affected males. They
emphasized the
occurrence of a 'peculiar curved linear dimple inferior to the lower
lip.' This
and other stigmata were present in an earlier female. They favored
sex-influenced autosomal dominant inheritance. Escobar
and Weaver (1978) reported a patient who had features more
suggestive of the
Noonan syndrome than of the Aarskog syndrome. The patient, aged 28
years, also
had severe macrocytic anemia refractory to iron therapy, hepatomegaly,
hemochromatosis, portal cirrhosis, and interstitial pulmonary disease. 
Berry
et al.
(1980) suggested that the first report of this syndrome was
that of Hanley
et al. (1967) who described brothers with multiple
osteochondritis dissecans
(165800).
The features were hypertelorism, cryptorchidism, digital contractures,
sternal
deformity, and osteochondritis dissecans at multiple sites. Early
fusion of the
manubrium and corpus sterni occurred. The ears were floppy; 'lop-ear'
or cup-ear
may be appropriately descriptive. One brother had ptosis. Grier
et al. (1981) observed typically affected father and son, a
situation that
probably clinches autosomal dominant inheritance (with sex influence)
for at
least one form of the disorder. The phenotype in both males was
classic. The
father was not related to the mother.
Tyrkus
et
al. (1980) described mother and son with Aarskog-Scott
syndrome. Expression
was complete in the mother. The mother and son had a reciprocal
translocation
between the X chromosome and chromosome 8. The breakpoint on the X was
at Xq12.
The mother's parents and sibs were clinically normal and the parents
had normal
karyotypes. Tyrkus
et al. (1980) described parental exposure to ionizing
radiation. They found
that the Aarskog-Scott locus may be located at Xq12. The normal X
chromosome in
the mother was consistently inactivated. Thus the full expression in
the mother
was explained. Bawle
et al. (1984) published definitively on the family in which a
balanced X-autosome
translocation was associated with Aarskog syndrome in mother and son.
They
placed the X chromosome breakpoint at Xq13. Noteworthy was the full
expression
in the mother comparable to the full expression of Duchenne muscular
dystrophy (310200)
in women with balanced X-autosome translocations involving Xp21. The
authors
postulated that, as in the latter case, the break at Xq13 creating the
translocation also caused a presumed de novo point mutation in the
'Aarskog
gene' and that the woman had nonrandom (preferential) inactivation of
her
structurally normal X. By high resolution cytogenetic studies, Rafael
et al. (1992) demonstrated that the X chromosome breakpoint
in the patient
of Bawle et al.
(1984) was located in the proximal short arm of the X
chromosome rather than
at Xq13. The autosomal breakpoint was 8q11 rather than 8p21.1, as
previously
reported. By study of somatic cell hybrids containing the der(X)
chromosome by a
combination of fluorescence in situ hybridization and Southern blot
analysis
with X-chromosome probes, Glover
et al. (1993) refined the localization of the breakpoint to
Xp11.21.
Van
den
Bergh et al. (1984) described a 17-year-old girl who
developed the syndrome
of benign intracranial hypertension after minor head trauma. A small
area of
congenital alopecia was found on the midline vertex and an underlying
bony
defect was revealed by skull x-rays. Cerebral angiography showed
absence of the
straight sinus and other abnormalities of cerebral venous drainage. A
9-year-old
brother showed full-blown Aarskog syndrome. The proband, her sister,
and her
mother showed signs interpreted as features of Aarskog syndrome. Friedman
(1985) described the distinctive umbilical changes of Aarskog
syndrome,
Rieger syndrome (180500),
and Robinow syndrome (180700).
He quoted the famous monograph on the umbilicus by Cullen
(1916), which had illustrations by Max Broedel. Two of 5
patients reported
by Tsukahara
and Fernandez (1994) had a protruding umbilicus and the other
3 had a
characteristic umbilicus consisting of a smooth depression with
radiating
branches of the cicatrix and a flat cushion.
Nielsen
(1988) reported the first Danish case of Aarskog syndrome in
a child who had
attended several specialized outpatient clinics before the diagnosis
was
suggested. In a review, Porteous
and Goudie (1991) reported that they knew of at least 12
affected persons in
a population of 1.6 million in the West of Scotland, but believed that
the true
incidence must be higher since the benign nature of the disorder
results in
underdiagnosis.
Mikelsaar
and Lurie (1992) described a boy with features typical of
Aarskog syndrome
who also had leg lymphedema extending to the knees when examined at the
age of
10 years. The lymphedema was presumably congenital but the age of onset
was not
stated. The mother had no features of the Aarskog syndrome, but the
maternal
grandfather showed hypertelorism, camptodactyly, and lymphedema of the
feet. Fryns
(1992) commented on the disappearance of manifestations in
postpubertal
males. Social integration and functioning as adults was usually
satisfactory. Fryns
(1993) described 2 unrelated males, aged 22 and 20, with
episodes of chronic
abdominal pain over several months. Investigations showed
dolichomegarectosigmoid ('long and large rectum and sigmoid'); in both,
sigmoid
resection with end-to-end reanastomosis was performed after acute
volvulus. For
further information concerning the 22-year-old patient, see Casteels
et al. (1994).
Fernandez
et
al. (1994) described 10 Japanese patients with Aarskog
syndrome from 3
families. One of these patients had pulmonary stenosis, and another had
ventricular septal defect. Analysis of the literature showed that
congenital
heart defects were described in 2 of 169 non-Japanese cases and in 2 of
20
previously reported Japanese cases. Fernandez
et al. (1994) suggested that cardiac evaluation is indicated
for all
children with Aarskog syndrome.
Fryns
(1992)
concluded that the incidence of mental handicap in Aarskog syndrome may
be as
high as 30%. Logie
and Porteous (1998) tested this observation in 21 males under
17 years of
age with clinically confirmed Aarskog syndrome and found their IQs to
lie within
the normal range. They concluded that Aarskog syndrome is not
associated with
mental handicap. On the other hand, Lebel
et al. (2002) found a missense mutation (305400.0005)
in the FGD1 gene in 3 brothers with nonsyndromal X-linked mental
retardation.
Although the brothers had short stature and small feet, they lacked
distinct
craniofacial, skeletal, or genital findings suggestive of Aarskog
syndrome.
Their mother was a carrier and was of normal intelligence.
Using
positional methods to clone the gene that is mutant in Aarskog-Scott
syndrome, Pasteris
et al. (1994) isolated YAC clones spanning the t(X;8)
breakpoint associated
with the disorder. The FGDY gene contains more than 19 exons spanning
100 kb.
The predicted length of the FGDY protein is 961 amino acids. It has
strong
homology to RAS-like RHO/RAC guanine nucleotide exchange factors
(GEFs), and
contains a cysteine-rich zinc finger-like region and 2 potential
SH3-binding
sites. Mutations in FGDY may result in perturbed signal transduction
and,
consequently, developmental growth anomalies. By SSCP analysis, Pasteris
et al. (1994) identified a mutation cosegregating with the
FGD1 gene in a
family with Aarskog-Scott syndrome; see 305400.0001.
Orrico
et
al. (2000) analyzed 13 unrelated patients with the clinical
diagnosis of
Aarskog-Scott syndrome. One patient carried an arg610-to-gln mutation (305400.0002)
located in 1 of the 2 pleckstrin homology (PH) domains of the FGD1
gene. It
corresponded to a highly conserved residue that had been involved in
phosphoinositide binding in PH domains of other proteins. Critical
missense
mutations within the PH domain of the Bruton tyrosine kinase gene (BTK;
300300)
result in X-linked agammaglobulinemia.
Using SSCP
analysis of the FGD1 gene, Schwartz
et al. (2000) identified a missense mutation (305400.0003)
in a familial case of Aarskog-Scott syndrome and a deletion mutation (305400.0004)
in a sporadic case. The authors were unable to detect alterations in
the FGD1
gene in propositi from 25 other familial cases, including the families
originally described by Aarskog
(1970) and Scott
(1971), or in 15 sporadic cases. They suggested that
mutational mechanisms
not detected using standard analysis of coding sequence genomic DNA may
cause
the disorder.
Orrico
et
al. (2004) performed SSCP analysis of the FGD1 gene in 46
male patients with
a clinical diagnosis of AAS. They identified 8 mutations, all novel,
including 4
deletions, 1 insertion, and 3 missense mutations. One mutation, 528insC
(305400.0006),
was found in 2 independent families. The mutations were scattered over
the
entire coding sequence, and there were no apparent genotype/phenotype
correlations. No global differences in clinical findings were found
between
probands with or without mutations, but those with mutations presented
with a
fuller clinical spectrum of the phenotype. Orrico
et al. (2004) concluded that mutations in the FGD1 gene
account for a
minority of X-linked AAS cases.
Pasteris
et
al. (1995) isolated the mouse Fgd1 homolog and mapped it to
the mouse X
chromosome. The mouse cDNA clones contained a 2,880-bp open reading
frame
predicted to encode a protein of 960 amino acids, 1 amino acid shorter
than the
human FGD1 open reading frame. Comparison of the mouse and human
sequences
within the coding region indicated 94.7% identity (96.3% similarity) at
the
amino acid level. Mapping information using interspecific backcross
analysis
indicated that Fgd1 lies between anchor loci as expected from
comparative human
and murine maps of the X chromosome. The results and observations
strongly
suggested to Pasteris
et al. (1995) that the mouse will serve as a useful model for
studying and
characterizing the Fgd1 development signal transduction system.
Zheng
et al.
(1996) reported that a fragment of the FGD1 protein
encompassing the PH and
Dbl (DH) homology domains binds specifically to the Rho GTPase cdc42 (116952)
and can stimulate the GDP-GTP exchange of the isoprenylated form of
cdc42. Cells
expressing this FGD1 fragment activated 2 elements downstream of cdc42,
namely,
Jun kinase (165160)
and p70 S6 kinase. The authors concluded that FGD1, through its PH and
DH
homology domains, acts as a cdc42-specific GDP-GTP exchange factor.
Estrada
et
al. (2001) used subcellular fractionation to show that
endogenous Fgd1
protein is localized in the cytosolic and Golgi and plasma membrane
fractions of
mouse calvarial cells. Immunocytochemical studies in mammalian cell
lines
confirmed the localization of Fgd1 and showed that the proline-rich
N-terminal
region is necessary and sufficient for Fgd1 subcellular localization to
the
plasma membrane and Golgi complex. Microinjection studies revealed that
the
N-terminal Fgd1 domain inhibits filopodia formation, suggesting that
this region
downregulates GEF function. The authors hypothesized that the Fgd1
Cdc42GEF
protein may be involved in the regulation of Cdc42 activity at the
subcortical
actin cytoskeleton and Golgi complex.
Gao
et al.
(2001) isolated and characterized fgd1, the C. elegans
homolog of the human
FGD1 gene. Comparative sequence analyses show that fgd1 and FGD1 share
a similar
structural organization and a high degree of sequence identity
throughout shared
signaling domains. Buechner
et al. (1999) had shown that several genes (designated Exc)
are involved in
excretory cell morphogenesis in nematodes. Interference with fgd1
expression
resulted in excretory cell abnormalities and cystic dilation of the
excretory
cell canals. Molecular lesions associated with 2 exc5 alleles affected
the fgd1
gene, and fgd1 transgenic expression rescued the Exc5 phenotype. The
authors
concluded that the fgd1 transcript corresponded to the exc5 gene.
Transgenic
expression studies showed that fgd1 has a limited pattern of expression
that is
confined to the excretory cell during development, a finding suggesting
that the
C. elegans FGD1 protein might function in a cell-autonomous manner.
Serial
observations indicated that fgd1 mutations lead to developmental
excretory cell
abnormalities that cause cystic dilation and interfere with canal
process
extension. The authors hypothesized that fgd1 plays a critical role in
excretory
cell morphogenesis and cellular organization.
In a family with 2 affected brothers and a carrier mother, Pasteris et al. (1994) used SSCP to demonstrate an insertion mutation in the FGD1 gene; an additional guanine residue after nucleotide 2122 resulted in a frameshift predicted to cause premature translation termination at codon 469.
In an Italian
family with faciogenital dysplasia, Orrico
et al. (2000) identified a 2559G-A transition in exon 10 of
the FGD1 gene,
resulting in an arg610-to-gln change in the protein product. The
mutation was
found to segregate with the Aarskog phenotype in affected males and
carrier
females. It was of particular interest because of involvement of the
pleckstrin
homology domain.
In 2 Italian
male cousins with Aarskog-Scott syndrome, Schwartz
et al. (2000) identified a 2296G-A alteration in the FGD1
gene, causing an
arg522-to-his change in the third structural conserved region of the
GEF domain
of the protein. The arginine at codon 522 is highly conserved, and the
bulkier
histidine probably alters the conformation of the GEF domain. The
mutation
eliminated an AciI restriction site in the normal sequence, which
segregated
with the syndrome in the family.
In a sporadic
case of Aarskog-Scott syndrome from Germany, Schwartz
et al. (2000) identified a deletion of 4 exons of the FGD1
gene. The exact
extent of the deletion was not determined, but at a minimum the altered
protein
lacked a portion of the GEF domain, a portion of a PH1 domain, and a
leucine
zipper domain.
Lebel
et al.
(2002) described 3 brothers with nonsyndromal X-linked mental
retardation
and a pro312-to-leu (P312L) missense mutation in the FGD1 gene.
Although the
brothers had short stature and small feet, they lacked distinct
craniofacial,
skeletal, or genital findings suggestive of Aarskog syndrome. Their
mother, the
only obligate carrier available for testing, had the FGD1 mutation. A
934C-T
base change in exon 4 was responsible for the P312L amino acid
substitution.
This missense mutation was predicted to eliminate a beta-turn, creating
an
extra-long stretch of coiled sequence that may affect the orientations
of the
SH3 binding domain and the first structural conserved region.
In a Belgian
and an Italian family, Orrico
et al. (2004) identified a 528insC mutation in the FGD1 gene,
causing a
frameshift after codon 176 and resulting in termination at codon 216.
The
mutation was associated with mild mental impairment in the Belgian
family but
was not associated with any neurodevelopmental disability in the
Italian family.
Baldellou et al. (1983); Berman et al. (1974); Fryns et al. (1978); Funderburk and Crandall (1974); Furukawa et al. (1972); Hoo (1979); Kodama et al. (1981); Oberiter et al. (1980); Pedersen et al. (1980)
Marla J. F.
O'Neill - updated : 5/6/2004
George E. Tiller - updated : 8/21/2002
Victor A. McKusick - updated : 5/10/2002
George E. Tiller - updated : 5/23/2001
Michael B. Petersen - updated : 1/12/2001
Victor A. McKusick - updated : 9/15/2000
Paul Brennan - updated : 2/18/1999
Jennifer P. Macke - updated : 4/8/1998
Iosif W. Lurie - updated : 8/11/1996
Victor A. McKusick : 6/4/1986
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=305400
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| Syndrome | Aarskog syndrome |
|---|---|
| Synonyms | Aarskog-Scott syndrome (ASS) |
| Greig syndrome | |
| facial-digital-genital syndrome | |
| facio-digito-genital syndrome | |
| facio-genital dysplasia | |
| shawl scrotum syndrome | |
| Personalia | Aarskog, Dagfinn (Norwegian pediatrician, born 1928) |
| Scott, Charles I., Jr. (American pediatrician) | |
| MeSH | Craniofacial Abnormalities |
| Hypertelorism | |
| Scrotum / abnormalities | |
| OMIM | 100050 |
| Summary | Multiple limb and genital abnormalities with short stature, hypertelorism, downslanting palpebral fissures, anteverted nostrils joint laxity, shawl scrotum, and occasional mental retardation. The phenotype varies with age and postpuberal males have only minor remnant manifestations of the prepuberal phenotype. |
| Major Features | Head and neck: A round face, broad forehead, hypoplastic ridging of the metopic sutures, and maxilla with relative mandibular prognathism are the main characteristics. |
| Ears: Thickeners and fleshiness of the earlobes. | |
| Eyes: Hypertelorism, enlarged corneal diameter, downslanting palpebral fissures, blepharoptosis, and ophthalmoplegia. | |
| Mouth and oral structures: A curved depression below the lover lip may be associated. | |
| Abdomen: Prominent umbilicus is frequent. | |
| Hand and foot: Tissue webbing between fingers and joint hypermobility with a pronounced hyperextension and flexion of the interphalangeal joints. Some patients exhibit fifth finger clinodactyly. The feet are flat, broad, and small with bulbous toes. Metatarsal abduction occurs in about half of all cases. Dermatoglyphic findings consist of single palmar creases. | |
| Extremities: Joint hyperlaxity. | |
| Spine: Spina bifida occulta, cervical vertebral defects, hypoplasia of the first cervical vertebra with unfused posterior arch, and subluxation of the first and second cervical vertebrae, | |
| Skin appendages: Widow's peak. | |
| Urogenital system: Shawl scrotum. | |
| Growth and development: Growth retardation. 30% of the affected males are mentally retarded. | |
| Behavior and performance: Hyperactivity and attention deficit are frequent. | |
| Heredity: Transmitted as an X-linked trait. Napped to the short arm of chromosome X (Xp11.22). | |
| Historical References | Aarskog D A familial syndrome of short stature associated with facial dysplasia and genital anomalies. Birth Defects, 1971, 7(6):235-9 |
| Aarskog D A familial syndrome of short stature associated with facial dysplasia and genital anomalies. J Pediat, 1970, 77:856-61 | |
| Ainsley RG Hypertelorism (Greig's syndrome). A case report. J Pediat Ophth, 1968, 5:148-50 | |
| Scott CI Jr Unusual facies, joint hypermobility, genital anomaly and short stature. A new dysmorphic syndrome. Birth Defects, 1971, 7(6):240-6 |
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Aug 2011
Aarskog–Scott syndrome is a rare X-linked recessive disorder with characteristic facial, skeletal, and genital abnormalities. We report on Aarskog–Scott syndrome in male dizygotic twins with an identical de novo mutation in FGD1 that resulted from germline mosaicism in the phenotypically normal mother. This is the first report of inheritance by germline mosaicism for the FGD1 gene.
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Medicina Molecolare, Azienda Ospedaliera Universitaria Senese, Siena, Italy. a.orrico@ao-siena.toscana.it
Mutations in the FGD1 gene have been shown to cause Aarskog-Scott syndrome (AAS), or facio-digito-genital dysplasia (OMIM#305400), an X-linked disorder characterized by distinctive genital and skeletal developmental abnormalities with a broad spectrum of clinical phenotypes. To date, 20 distinct mutations have been reported, but little phenotypic data are available on patients with molecularly confirmed AAS. In the present study, we report on our experience of screening for mutations in the FGD1 gene in a cohort of 60 European patients with a clinically suspected diagnosis of AAS. We identified nine novel mutations in 11 patients (detection rate of 18.33%), including three missense mutations (p.R402Q; p.S558W; p.K748E), four truncating mutations (p.Y530X; p.R656X; c.806delC; c.1620delC), one in-frame deletion (c.2020_2022delGAG) and the first reported splice site mutation (c.1935+3A>C). A recurrent mutation (p.R656X) was detected in three independent families. We did not find any evidence for phenotype-genotype correlations between type and position of mutations and clinical features. In addition to the well-established phenotypic features of AAS, other clinical features are also reported and discussed.
............................
............................
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Cerebrovascular disease associated with Aarskog-Scott syndrome.
Neuroradiology. 2007 May
............................
Unusually severe expression of craniofacial features in Aarskog-Scott syndrome due to a novel truncating mutation of the FGD1 gene.
Am J Med Genet A. 2007 Jan
............................
Female counterpart of shawl scrotum in Aarskog-Scott syndrome.
Int Braz J Urol. 2006 Jul-Aug
International Brazilian Journal of Urology
............................
Clinical variation of Aarskog syndrome in a large family with 2189delA in the FGD1 gene.
Am J Med Genet A. 2006 Jan
............................
Aarskog syndrome
2002
===========================
Support Group and resources:
The Aarskog Syndrome Parents Support Group's purpose is to educate the public about the features and possible delays or learning difficulties that may or may not effect some of children with Aarskog Syndrome and to offer support by mail or phone when needed.
The Support Group publishes a yearly newsletter, Aarskog News, for a minimal fee. The newsletter has a parent contact page for those wishing to get in touch with others who are affected by Aarskog. A new parent packet is available and contains past newsletters and articles that are on file. There is an article file containing writings by doctors on this syndrome from genetic books. There is a form available for those who wish to order specific articles.
Other resources and help
Children's Craniofacial Association13140 Coit Road
Dallas TX 75240
Phone #: 214-570-9099
800 #: 800-535-3643
e-mail: contactcca@ccakids.com
Home page: http://www.ccakids.com
MAGIC Foundation for Children's Growth
6645 W. North Avenue
Oak Park IL 60302
Phone #: 708-383-0808
800 #: 800-362-4423
e-mail: mary@magicfoundation.org
Home page: http://www.magicfoundation.org
March of Dimes Birth Defects Foundation
1275 Mamaroneck Avenue
White Plains NY 10605
Phone #: 914-428-7100
800 #: 888-663-4637
e-mail: Askus@marchofdimes.com
Home page: http://www.marchofdimes.com
NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases
1 AMS Circle
Bethesda MD 20892-3675
Phone #: 301-496-8188
800 #: 877-226-4267
e-mail: NAMSIC@mail.nih.gov
Home page: http://www.nih.gov/niams/
National Craniofacial Foundation
3100 Carlisle Street
Dallas TX 75204
Phone #: --
800 #: 800-535-3643
e-mail: N/A
Home page: N/A
World Cranofacial Foundation
Home Page: http://www.worldcf.org/sections/resources/default.asp
Contact: contact Rebecca Rhule at rebecca@worldcf.org or 972.566.2497.
===========================
Aarskog-Scott syndrome
Classification and external resources:
=========
ICD-10
| Q87.1 | Congenital malformation syndromes predominantly associated with short stature | |||||||
| Syndrome: · Aarskog · Cockayne · De Lange · Dubowitz · Noonan · Prader-Willi · Robinow-Silverman-Smith · Russell-Silver · Seckel · Smith-Lemli-Opitz |
||||||||
| Excludes: | Ellis-van Creveld syndrome |
|||||||
ICD-9
OMIM - 100050
DiseaseDB - 29329
===========================
Join us as we work for lymphedema patients everywehere:
Advocates for Lymphedema
Dedicated to be an advocacy group for lymphedema patients. Working towards education, legal reform, changing insurance practices, promoting research, reaching for a cure.
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Pat O'Connor
Lymphedema People / Advocates for Lymphedema
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===========================
Lymphedema People - Support Groups
-----------------------------------------------
Children
with Lymphedema
The time has come for families, parents, caregivers to have a support
group of
their own. Support group for parents, families and caregivers of
chilren with
lymphedema. Sharing information on coping, diagnosis, treatment and
prognosis.
Sponsored by Lymphedema People.
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Lipedema
Lipodema Lipoedema
No matter how you spell it, this is another very little understood and
totally
frustrating conditions out there. This will be a support group for
those
suffering with lipedema/lipodema. A place for information, sharing
experiences,
exploring treatment options and coping.
Come join, be a part of the family!
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Subscribe: lipedema_lipodema_lipoedema-subscribe@yahoogroups.com
......................
MEN WITH LYMPHEDEMA
If you are a
man with lymphedema; a man with a loved one with lymphedema who you are
trying
to help and understand come join us and discover what it is to be the
master
instead of the sufferer of lymphedema.
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Subscribe: menwithlymphedema-subscribe@yahoogroups.com
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All
About Lymphangiectasia
Support group for parents, patients, children who suffer from all forms
of
lymphangiectasia. This condition is caused by dilation of the
lymphatics. It can
affect the intestinal tract, lungs and other critical body areas.
http://health.groups.yahoo.com/group/allaboutlymphangiectasia/
Subscribe: allaboutlymphangiectasia-subscribe@yahoogroups.com
......................
Lymphatic
Disorders Support Group @ Yahoo Groups
While we have a number
of support groups for lymphedema... there is nothing out there for
other
lymphatic disorders. Because we have one of the most comprehensive
information
sites on all lymphatic disorders, I thought perhaps, it is time that
one be
offered.
DISCRIPTION
Information and support for rare and unusual disorders affecting the
lymph
system. Includes lymphangiomas, lymphatic malformations,
telangiectasia,
hennekam's syndrome, distichiasis, Figueroa
syndrome, ptosis syndrome, plus many more. Extensive database of
information
available through sister site Lymphedema People.
http://health.groups.yahoo.com/group/lymphaticdisorders/
Subscribe: lymphaticdisorders-subscribe@yahoogroups.com
......................
===========================
Lymphedema People New Wiki Pages
Have you seen
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pages
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are just a sample
of the more than 140 pages now listed in our Wiki section. We are also
working
on hundred more. Come
and take a
stroll!
Lymphedema
Glossary
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Lymphedema
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Exercises for
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Diuretics are
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Lymphedema
People Online Support Groups
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Lipedema
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Treatment
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Manual
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Infections
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How to Treat a
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Fungal
Infections Associated with Lymphe
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Lymphedema in
Children
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_in_children
Lymphoscintigraphy
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Magnetic
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Extraperitoneal
para-aortic lymph node dissection (EPLND)
Axillary
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Lymphedema
Gene FOXC2
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Lymphedema Gene VEGFC
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Lymphedema Gene SOX18
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_gene_sox18
Lymphedema
and Pregnancy
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Home page: Lymphedema People
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Page Updated: Nov. 28, 2011