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.
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 brain
Difficulty growing in the first year of life
Poorly aligned teeth
There is no "treatment" for the main condition. Treatment would focus on the clinical features and complications.
May 26, 2008
Clinical and General Information:
DefinitionAarskog syndrome is an inherited disease characterized by short stature, facial abnormalities, musculoskeletal, and genital anomalies.
Causes, incidence, and risk factorsAarskog 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.
Signs and testsX-rays will reveal skeletal abnormalities. Genetic testing may be available for mutations in the FGDY1 gene.
TreatmentOrthodontic 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.
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.
ComplicationsSome 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 providerCall 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.
PreventionThere 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.
Synonyms of Aarskog Syndrome
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.
Abstracts and Studies:
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.
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. email@example.com
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.
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.
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
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
Alternative titles; symbolsFGDY
Aarskog (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
|Synonyms||Aarskog-Scott syndrome (ASS)|
|shawl scrotum syndrome|
|Personalia||Aarskog, Dagfinn (Norwegian pediatrician, born 1928)|
|Scott, Charles I., Jr. (American pediatrician)|
|Scrotum / abnormalities|
|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|
Medicina Molecolare, Azienda Ospedaliera Universitaria Senese, Siena, Italy. firstname.lastname@example.org
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.
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
Clinical variation of Aarskog syndrome in a large family with 2189delA in the FGD1 gene.
Am J Med Genet A. 2006 Jan
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 helpChildren's Craniofacial Association
13140 Coit Road
Dallas TX 75240
Phone #: 214-570-9099
800 #: 800-535-3643
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
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
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
Home page: http://www.nih.gov/niams/
National Craniofacial Foundation
3100 Carlisle Street
Dallas TX 75204
Phone #: --
800 #: 800-535-3643
Home page: N/A
World Cranofacial Foundation
Contact: contact Rebecca Rhule at email@example.com or 972.566.2497.
Classification and external resources:
|Q87.1||Congenital malformation syndromes predominantly associated with short stature|
· De Lange
|Excludes:||Ellis-van Creveld syndrome
OMIM - 100050
DiseaseDB - 29329
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Lymphatic Drainage (MLD) and Complex Decongestive Therapy (CDT)
Associated with Lymphedema
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Infections Associated with Lymphe dema
para-aortic lymph node dissection (EPLND)
Needle Biopsy - Fine Needle Aspiration
Lymphedema Gene VEGFC
Lymphedema Gene SOX18
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Page Updated: Nov. 28, 2011