U.S. flag

An official website of the United States government

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Adam MP, Bick S, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026.

Cover of GeneReviews®

GeneReviews® [Internet].

Show details

FGD1-Related Faciogenital Dysplasia (Aarskog-Scott Syndrome)

Synonyms: Aarskog-Scott Syndrome, Aarskog Syndrome, Faciogenital Dysplasia

, MD, PhD.

Author Information and Affiliations

Initial Posting: .

Estimated reading time: 26 minutes

Summary

Clinical characteristics.

FGD1-related faciogenital dysplasia (Aarskog-Scott syndrome) is characterized by distinctive craniofacial features (including broad forehead, widow's peak and/or frontal upsweep, hypertelorism, ptosis, short nose with a broad nasal bridge and anteverted nares, wide mouth, and rectangular thickening of the ear lobes), short stature, skeletal anomalies (including short/broad hands, brachydactyly, camptodactyly, "swan neck" finger deformities, prominent interphalangeal joints, and metatarsus varus), genital anomalies including shawl scrotum and cryptorchidism, dental anomalies, variable neurodevelopmental disorders, ophthalmologic findings, and inguinal hernia. Congenital malformations such as cardiac defects, central nervous system anomalies, and cleft lip and/or palate are less common. Heterozygous females are typically asymptomatic or show a milder, incomplete phenotype.

Diagnosis/testing.

The diagnosis of Aarskog-Scott syndrome is established in a male proband with characteristic clinical findings and a hemizygous FGD1 pathogenic variant identified by molecular genetic testing. The diagnosis of Aarskog-Scott syndrome can be established in a female proband with characteristic clinical findings (milder, incomplete phenotype) and a heterozygous FGD1 pathogenic variant identified by molecular genetic testing; Heterozygous females are typically asymptomatic.

Management.

Treatment of manifestations: Growth hormone therapy may be considered in those with growth hormone deficiency or persistent growth deficiency in those born small for gestational age without catch-up growth; standard orthopedic management for camptodactyly, foot malposition, and osteochondritis; standard treatment for cryptorchidism; standard dental and orthodontic care; developmental and educational support; standard ophthalmologic management of vision issues; ptosis surgery if visual axis is obstructed; standard management of hernias and anorectal anomalies; standard treatment of congenital heart disease; surgical correction for cleft lip and palate; speech therapy when needed.

Surveillance: Measurement of growth parameters at every visit until adulthood; clinical musculoskeletal examination annually or as needed; monitor testicular descent at each pediatric visit; dental evaluations beginning with tooth eruption then annually or as clinically indicated; monitor developmental progress, educational needs, and for attention-deficit/hyperactivity disorder at each visit; ophthalmology evaluation annually in childhood and adolescence or as clinically indicated; assess for inguinal hernia at each visit; follow-up echocardiography as indicated by cardiologist; follow up for cleft lip/palate as clinically indicated; audiology evaluation annually in childhood and adolescence or as clinically indicated.

Agents/circumstances to avoid: Avoid movements that cause sudden stress to the head and neck (e.g., somersaults, head dives, high-force cervical manipulation) and neck hyperextension during procedures until cervical abnormalities have been ruled out. Obtain cervical spine radiographs before general anesthesia.

Evaluation of relatives at risk: It is appropriate to clarify the genetic status of apparently asymptomatic older and younger at-risk male relatives of an affected individual in order to identify as early as possible those who would benefit from echocardiogram and management of congenital heart disease.

Genetic counseling.

Aarskog-Scott syndrome is inherited in an X-linked manner. About 10% of affected males have the disorder as the result of a de novo pathogenic variant. If the mother of the proband has an FGD1 pathogenic variant, the chance of the mother transmitting it in each pregnancy is 50%. Males who inherit the pathogenic variant will be affected. Females who inherit the pathogenic variant will be heterozygotes and will usually be asymptomatic or have a partial or milder phenotype. Affected males transmit the FGD1 pathogenic variant to all of their daughters and none of their sons. Once the FGD1 pathogenic variant has been identified in an affected family member, identification of female heterozygotes and prenatal/preimplantation genetic testing are possible.

Diagnosis

For the purposes of this GeneReview, the terms "male" and "female" are narrowly defined as the individual's biological sex at birth as it determines clinical care [Caughey et al 2021].

Clinical diagnostic criteria for FGD1-related faciogenital dysplasia (Aarskog-Scott syndrome) have been published [Zanetti Drumond et al 2021]. These criteria do not have consensus, and in current practice, diagnosis is established by the identification of a pathogenic variant in FGD1.

Suggestive Findings

Aarskog-Scott syndrome should be suspected/considered in probands with the following clinical findings and family history.

Clinical findings

  • Characteristic craniofacial features including broad forehead, widow's peak, hypertelorism, short nose, anteverted nares, wide mouth, and rectangular thickening of the ear lobes (See Figure 1.)
  • Mild-to-moderate short stature, often with prenatal onset
  • Skeletal anomalies including limb shortening, brachydactyly, camptodactyly, "swan neck" deformity of the fingers, metatarsus varus, osteochondritis, pectus excavatum, and scoliosis (See Figure 1.)
  • Genital anomalies, especially shawl scrotum (redundant scrotal skin surrounding the penile base) and cryptorchidism
  • Dental anomalies including crowding, agenesis, abnormal tooth morphology, and delayed eruption
  • Neurodevelopmental disorders with variable severity, including speech delay, attention-deficit disorder with or without hyperactivity, executive function difficulties, and specific learning disorders. Intellectual disability is rare.
  • Ophthalmologic findings such as high hyperopia, strabismus, and ptosis
  • Variable congenital anomalies such as congenital heart defects and cleft lip and/or palate
Figure 1.

Figure 1.

Extremities and ears morphology in FGD1-related faciogenital dysplasia (Aarskog-Scott syndrome) Characteristic findings include short and broad hands with brachydactyly, camptodactyly, “swan-neck” finger deformities, prominent proximal (more...)

Family history is consistent with X-linked inheritance (e.g., no male-to-male transmission). Absence of a known family history does not preclude the diagnosis.

Establishing the Diagnosis

Male proband. The diagnosis of Aarskog-Scott syndrome is established in a male proband with suggestive findings and a hemizygous pathogenic (or likely pathogenic) variant in FGD1 identified by molecular genetic testing (see Table 1).

Female proband. The diagnosis of Aarskog-Scott syndrome is usually established in a female proband with suggestive findings and a heterozygous pathogenic (or likely pathogenic) variant in FGD1 identified by molecular genetic testing (see Table 1).

Note: (1) Per American College of Medical Genetics and Genomics (ACMG) / Association for Molecular Pathology variant interpretation guidelines, the terms "pathogenic variant" and "likely pathogenic variant" are synonymous in a clinical setting, meaning that both are considered diagnostic and can be used for clinical decision making [Richards et al 2015]. Reference to "pathogenic variants" in this GeneReview is understood to include likely pathogenic variants. (2) Identification of a hemizygous/heterozygous FGD1 variant of uncertain significance does not establish or rule out the diagnosis.

Molecular genetic testing approaches can include a combination of gene-targeted testing (single gene testing, multigene panel) and comprehensive genomic testing (exome sequencing, genome sequencing). Gene-targeted testing requires that the clinician determine which gene(s) are likely involved (see Option 1), whereas comprehensive genomic testing does not (see Option 2).

Option 1

When the phenotypic findings suggest the diagnosis of Aarskog-Scott syndrome, molecular genetic testing approaches can include single-gene testing or use of a multigene panel.

  • Single-gene testing. Sequence analysis of FGD1 is performed first to detect missense, nonsense, and splice site variants and small intragenic deletions/insertions. Note: Depending on the sequencing method used, single-exon, multiexon, or whole-gene deletions/duplications may not be detected. If no variant is detected by the sequencing method used, the next step is to perform gene-targeted deletion/duplication analysis to detect exon and whole-gene deletions or duplications.
  • A multigene panel that includes FGD1 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition while limiting identification of pathogenic variants and variants of uncertain significance in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
    For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.

Option 2

When the diagnosis of Aarskog-Scott syndrome has not been considered because an individual has atypical phenotypic features, comprehensive genomic testing does not require the clinician to determine which gene is likely involved. Exome sequencing is most commonly used; genome sequencing is also possible. ACMG and the American Academy of Pediatrics recommend exome/genome sequencing as first- or second-tier diagnostic testing for children with developmental delay, intellectual disability, and/or multiple congenital anomalies [Manickam et al 2021, Rodan et al 2025]. To date, the majority of FGD1 pathogenic variants reported (e.g., missense, nonsense) are within the coding region and are likely to be identified on exome sequencing. Rarely, deep intronic variants have been identified [Aten et al 2013].

For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.

Table 1.

FGD1-Related Faciogenital Dysplasia (Aarskog-Scott Syndrome): Molecular Genetic Testing

Gene 1MethodProportion of Pathogenic Variants 2 Identified by Method
FGD1 Sequence analysis 390% 4, 5
Gene-targeted deletion/duplication analysis 610% 4, 7
1.
2.

See Molecular Genetics for information on variants detected in this gene.

3.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include missense, nonsense, and splice site variants and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

4.

Orrico et al [2015], Jeanne et al [2025], and data derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2020]

5.

FGD1 deep intronic pathogenic variants have been identified; sequence analysis that detects these deep intronic variants should be considered [Aten et al 2013].

6.

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. Exome and genome sequencing may be able to detect deletions/duplications using breakpoint detection or read depth; however, sensitivity can be lower than gene-targeted deletion/duplication analysis.

Clinical Characteristics

Clinical Description

FGD1-related faciogenital dysplasia (Aarskog-Scott syndrome) is characterized by short stature, distinctive facial features (including hypertelorism, ptosis, anteverted nares, wide mouth, thickened ear lobes), skeletal anomalies including camptodactyly and metatarsus varus, variable neurodevelopmental disorders, and variable congenital malformations in affected males. Heterozygous females are typically asymptomatic or show a milder, incomplete phenotype. To date, less than 200 individuals have been identified with a pathogenic variant in FGD1 [Zanetti Drumond et al 2021, Jeanne et al 2025]. The following description of the phenotypic features associated with this condition is based on these reports.

Affected Males

Table 2.

FGD1-Related Faciogenital Dysplasia (Aarskog-Scott Syndrome): Frequency of Select Features

Feature% of Persons w/FeatureComment
Distinctive facial features>95%Hypertelorism, short nose w/anteverted nares, wide mouth, rectangular thickening of ear lobes
Hand anomalies>90%Short/broad hands, brachydactyly, camptodactyly, ”swan neck" finger deformities, prominent proximal interphalangeal joints
Short stature80%-90%Prenatal onset in 50%; tends to normalize in 2nd decade
Foot malposition / metatarsus varus>70%
Genital anomalies80%Shawl scrotum & cryptorchidism
Dental anomalies80%Crowding, malocclusion
Learning difficulties70%
Speech delay40%
ADHD10%-30%
Intellectual disability16%Typically mild
Eye issues>50%Hyperopia, ptosis, strabismus
Inguinal hernia30%-40%
Heart defects16%Mostly ventricular & atrial septal defects; aortic dilatation has been described
Brain malformations10%Thick corpus callosum, enlarged ventricles, & gyration abnormalities
Cleft lip & palate6%

ADHD = attention-deficit/hyperactivity disorder

Characteristic craniofacial features. The facial gestalt typically includes a broad forehead a with a widow's peak and/or frontal upsweep, marked ocular hypertelorism (~95%), unilateral or asymmetric ptosis, flat midface, a short nose with a broad nasal bridge and anteverted nares, a long/wide philtrum, wide mouth, an everted vermilion of the lower lip with a horizontal crease below the vermilion border of the lower lip, and small, low-set, posteriorly rotated ears with a characteristic rectangular thickening of the ear lobe (~90%). Downslanted palpebral fissures (~50%), laterally sparse eyebrows (~70%), and a wavy upper lip when smiling (~75%) are common [Zanetti Drumond et al 2021, Jeanne et al 2025]. Dysmorphism is evident at birth, and in some individuals specific features can be detected on prenatal ultrasound, most commonly hypertelorism (~10%) [Jeanne et al 2025].

Growth deficiency. Intrauterine growth restriction and shortened long bones are reported in approximately 45% and 60% of pregnancies, respectively.

Birth length is below the 10th centile in approximately 60% of individuals. Postnatally, short stature is common (70%-80%) and is more pronounced in early childhood, with a height ranging from 4.1 standard deviations (SD) below the mean to 1.3 SD above the mean. Growth patterns often show an acceleration of growth velocity toward the end of the first decade and through puberty. The mean adult height is within the low-normal range (164 cm; 1.7 SD below the mean; range: 154-172 cm) [Pavone et al 2020, Zanetti Drumond et al 2021, Jeanne et al 2025]. To date, it is unclear whether growth hormone therapy can increase the height potential of affected individuals [Satoh & Yokoya 2006, Zanetti Drumond et al 2021, Jeanne et al 2025].

Skeletal anomalies. Individuals with Aarskog-Scott syndrome almost consistently present with short and broad hands with brachydactyly. Camptodactyly, "swan neck" finger deformities, and prominent proximal interphalangeal joints with redundant skin folds are present in half of individuals. Additional hand findings include a single transverse palmar crease, a single flexion crease of the fifth finger, and partial cutaneous syndactyly (~40%) [Griffin et al 2016, Zanetti Drumond et al 2021, Jeanne et al 2025].

Foot anomalies are common, with metatarsus varus being the most prevalent (~70%). Other features include short and broad feet with broad halluces and short toes [Griffin et al 2016, Jeanne et al 2025].

Other skeletal features include brachymelia (~60%), short and broad neck (~60%), pectus excavatum (~40%), scoliosis (~10%), and mild-to-moderate joint hypermobility. Osteochondritis appears more prevalent than in the general population, and severe forms (osteochondritis dissecans) have been reported [Jeanne et al 2025].

Radiographs show recurring features including brachymetacarpia, brachymetatarsia, hypoplastic distal phalanges, brachymesophalangy of the fifth finger, and cone-shaped epiphyses. Axial findings can include thickening of the medial clavicles, short and broad femoral necks with coxa valga, and small femoral epiphyses [Jeanne et al 2025].

Although vertebral anomalies were described as frequent in historical, non-molecularly confirmed series, recent cohorts of molecularly confirmed individuals suggest that they are uncommon (~4%), typically stable, and asymptomatic [Lizcano-Gil et al 1994, Fryns 1992, Jeanne et al 2025]. Their frequency may be underestimated because radiographs have not been obtained systematically. Reported anomalies include spinal canal narrowing and cervical anomalies such as posterior arch hypoplasia and vertebral fusion.

Genital anomalies. The most characteristic genital feature is the shawl scrotum (redundant scrotal skin surrounding the penile base), observed in about 80% of affected males. Cryptorchidism is also common (50%-70%), while micropenis (~10%) and hypospadias (~4%) are less frequent [Zanetti Drumond et al 2021, Jeanne et al 2025].

Dental anomalies. Dental anomalies are common and likely underrecognized, affecting about 80% of individuals. The most frequent findings are dental crowding (50%), delayed eruption (35%), and malocclusion (22%). Additional features include large maxillary central incisors (~22%), taurodontism (16%), ectopic teeth (12%), and atypical tooth shape (11%) [Depeyre et al 2018, Jeanne et al 2025].

Development/cognition. Neonatal hypotonia is uncommon (~14%) and early development is typically normal except for a mild language delay in approximately half of affected individuals [Orrico et al 2010, Zanetti Drumond et al 2021, Jeanne et al 2025]. The average age for independent walking is around 16 months (range: 11-28 months) [Jeanne et al 2025].

Mild intellectual disability is uncommon (~16%). In a limited subset of affected individuals, full-scale IQ was approximately 76 (range: 69-106) and standardized evaluations revealed significant deficits in executive functions [Verhoeven et al 2012, Jeanne et al 2025]. Learning difficulties are frequent (~70%) and attention-deficit/hyperactivity disorder (ADHD) and specific learning disorders (dyslexia/dysgraphia/dyscalculia) affect approximately 30% of individuals [Jeanne et al 2025]. Neurodevelopmental difficulties tend to improve in adulthood [Orrico et al 2004, Jeanne et al 2025].

Ophthalmologic findings. Refractive errors are frequent and dominated by high hyperopia (~50%) often with astigmatism. Strabismus and ptosis (typically unilateral or asymmetric) occur in about one third of individuals [Jeanne et al 2025].

Inguinal hernia occurs in one third of affected individuals [Zanetti Drumond et al 2021, Jeanne et al 2025].

Cardiac defects occur in more than 15% but are usually benign, mostly septal defects [Jeanne et al 2025]. Importantly, aortic root dilatation has been documented including a severe form requiring surgery in an adult with Aarskog-Scott syndrome.

Central nervous system anomalies. Although only a few individuals had brain imaging, central nervous system anomalies have been described. They include a thick corpus callosum (three individuals, including two fetuses), ventriculomegaly (two individuals), and gyration abnormalities (two individuals) [Bottani et al 2007, Jeanne et al 2025]. Additionally, two individuals with cerebral vascular dysplasia have been described. One had right occipital sinus pericrania associated with agenesis of the left lateral venous sinus and the other had a cerebral cavernoma [Jeanne et al 2025].

Cleft lip and/or palate is uncommon (~6%).

Prenatal. Prenatal manifestations are common but nonspecific. In about half of pregnancies, ultrasounds show intrauterine growth restriction and/or short long bones [Jeanne et al 2025]. Less frequent findings include clubfoot / foot malposition and facial dysmorphism, most often hypertelorism (~10%). Associated malformations such as congenital heart defect and cleft lip/palate are typically expected to be detected prenatally but have rarely been documented. Overall, prenatal signs are insufficiently specific unless there is a known family history.

Less common findings

  • Anal anomalies have been reported in four individuals, ranging from anal stenosis or imperforate anus to severe anterior placement requiring surgery [Jeanne et al 2025].
  • Myopathic symptoms consisting of exercise intolerance and muscle pain have been reported in a few individuals with Aarskog-Scott syndrome [Al-Semari et al 2013, Bayat et al 2022, Jeanne et al 2025]. Mitochondrial dysfunction has been suspected as the underlying mechanism [Bayat et al 2022].

Heterozygous Females

To date, there is insufficient data to determine the exact proportion of symptomatic heterozygous females. However, it seems that most heterozygous females are asymptomatic or have a partial or milder phenotype. Short stature (height more than 2 SD below the mean) occured in approximately 17% and the mean adult height was 159 cm (0.75 SD below the mean) in 54 heterozygous females of the largest published series [Jeanne et al 2025]. Frequently reported manifestations include hand anomalies (short/broad hands, "swan neck" finger deformities, camptodactyly, partial cutaneous syndactyly) and partial facial features (e.g., hypertelorism, widow's peak, anteverted nares, thin vermilion of the upper lip) [Jeanne et al 2025]. While uncommon, neurodevelopmental concerns have been reported, including learning difficulties, language delay, and ADHD. One heterozygous female was noted to have a congenital heart defect (atrial septal defect) [Jeanne et al 2025].

Genotype-Phenotype Correlations

No clinically relevant genotype-phenotype correlations have been identified [Orrico et al 2015, Jeanne et al 2025].

Prevalence

The true prevalence is unknown. To date, fewer than 200 individuals with a molecularly confirmed FGD1 pathogenic variant have been reported in the literature.

Differential Diagnosis

Genetic disorders associated with similar facial features, short stature, and variable genital and other congenital anomalies in the differential diagnosis of FGD1-related faciogenital dysplasia (Aarskog-Scott syndrome) are listed in Table 3.

Table 3.

FGD1-Related Faciogenital Dysplasia (Aarskog-Scott Syndrome): Genetic Differential Diagnosis

Gene(s) / Genetic MechanismDisorder 1MOIFeatures Similar to Aarskog-Scott SyndromeFeatures Distinct from Aarskog-Scott Syndrome
BRAF
KRAS
LZTR1
MAP2K1
MRAS
NRAS
PTPN11
RAF1
RASA2
RIT1
RRAS2
SOS1
SOS2 		Noonan syndrome AD
(AR) 2
  • Short stature
  • Facial features (incl ptosis)
  • Mild neurodevelopmental impairment
  • Cryptorchidism
  • Pulmonary valve stenosis
  • Hypertrophic cardiomyopathy
  • Shawl scrotum uncommon
CDH11
SPECC1L 		Teebi hypertelorism syndrome (OMIM PS145420)AD
  • Facial features
  • Cleft lip/palate (much more frequent in Teebi hypertelorism syndrome)
  • No limb anomalies
  • Genital anomalies uncommon
DVL1
DVL3
WNT5A 		Autosomal dominant Robinow syndrome AD
  • Facial features
  • Short stature
  • Normal neurodevelopment
  • Macrocephaly
  • Shawl scrotum uncommon
ROR2 ROR2-related Robinow syndrome AR
  • Facial features
  • Short stature
  • Brachydactyly
  • Macrocephaly
  • Vertebral segmentation anomalies
  • More severe skeletal features
  • Shawl scrotum uncommon
ANKRD11 (PV in ANKRD11 or deletion of 16q24.3 incl ANKRD11) KBG syndrome AD
  • Facial features
  • Macrodontia
  • Brachydactyly
  • Short stature
  • Shawl scrotum absent
  • Seizures
1.

Disorders are ordered by relevance, with diagnoses most similar to Aarskog-Scott syndrome listed first.

2.

Noonan syndrome is most often inherited in an autosomal dominant manner. Noonan syndrome caused by pathogenic variants in LZTR1 can be inherited in either an autosomal dominant or an autosomal recessive manner.

Management

No clinical practice guidelines for FGD1-related faciogenital dysplasia (Aarskog-Scott syndrome) have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with Aarskog-Scott syndrome, the evaluations summarized in Table 4 (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 4.

FGD1-Related Faciogenital Dysplasia (Aarskog-Scott Syndrome): Recommended Evaluations Following Initial Diagnosis

System/ConcernEvaluationComment
Growth/
Endocrine
  • Measurement of growth parameters
  • Pubertal staging
  • Bone age & GH axis testing if height >2 SD below mean
Consider endocrinology referral if height >2 SD below mean.
Musculoskeletal
  • Musculoskeletal exam for camptodactyly, foot malposition (metatarsus varus / clubfoot), scoliosis
  • Assessment of cervical spine mobility
  • Radiographs & additional imaging as needed for osteochondritis dissecans when symptomatic
  • Cervical spine radiographs are recommended before general anesthesia.
Genitourinary
  • Assessment for undescended testes & genital hypoplasia
  • Referral to urologist as needed
Shawl scrotum has no clinical implication.
Dental Dental evalTo assess for crowding, eruption delay, malocclusion
Development
  • Assessment of developmental milestones, incl speech eval
  • Neuropsychological testing as needed
  • ADHD screening
Eyes Ophthalmologic evalTo assess for amblyopia, hyperopia, strabismus, & ptosis
Gastrointestinal Assessment for inguinal hernia & anorectal malformationsAnorectal malformations are rare.
Cardiovascular EchocardiographyTo identify congenital heart defects (often septal defects, aortic root dilatation)
Neurology Brain MRI ± MR angiography if severe neurodevelopmental disorder, focal deficits, refractory headaches, &/or seizures
ENT/Craniofacial Assessment for cleft lip/palateReferral to audiologist if speech delay or cleft
Genetic counseling By genetics professionals 1To obtain a pedigree & inform affected persons & their families re nature, MOI, & implications of Aarskog-Scott syndrome to facilitate medical & personal decision making
Family support
& resources 		By clinicians, wider care team, & family support organizationsAssessment of family & social structure to determine need for:

ADHD = attention-deficit/hyperactivity disorder; GH = growth hormone; MOI = mode of inheritance; SD = standard deviations

1.

Clinical geneticist, certified genetic counselor, certified genetic nurse, genetics advanced practice provider (nurse practitioner or physician assistant)

Treatment of Manifestations

Supportive care to improve quality of life, maximize function, and reduce complications is recommended. This ideally involves multidisciplinary care by specialists in relevant fields (see Table 5).

Table 5.

FGD1-Related Faciogenital Dysplasia (Aarskog-Scott Syndrome): Treatment of Manifestations

Manifestation/ConcernTreatmentConsiderations/Other
Short stature GH therapy may be considered if criteria are met (documented GH deficiency or persistent growth deficiency in those born SGA w/o catch-up growth)
  • Consider delaying GH therapy initiation in those w/mild short stature w/o GH deficiency (natural history suggests catch-up growth in late childhood).
  • Monitor for osteochondritis in those on GH.
Camptodactyly Orthopedic mgmt per standard proceduresFavorable outcomes are common w/conservative care.
Foot malposition (metatarsus varus / clubfoot)
Osteochondritis Standard mgmt per orthopedist
Cryptorchidism Standard treatment per urologist
Dental anomalies Standard dental/orthodontic care per dentist/orthodontist
Developmental delay / Intellectual disability / Neurobehavioral issues See Developmental Delay / Intellectual Disability Management Issues.
Abnormal vision & ptosis
  • Standard treatment(s) as recommended by ophthalmologist
  • Ptosis surgery if visual axis obstructed
Community vision services through early intervention or school district
Gastrointestinal Hernia &/or anorectal mgmt per standard procedures
Congenital heart disease Standard treatment per cardiologist
Cleft lip/palate Surgical correction &/or speech therapy may be requiredAs per multidisciplinary cleft team

GH = growth hormone; SGA = small for gestational age

Developmental Delay / Intellectual Disability Management Issues

The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country.

Ages 0-3 years. Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy as well as infant mental health services, special educators, and sensory impairment specialists. In the US, early intervention is a federally funded program available in all states that provides in-home services to target individual therapy needs.

Ages 3-5 years. In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed for those who qualify based on established motor, language, social, or cognitive delay. The early intervention program typically assists with this transition. Developmental preschool is center based; for children too medically unstable to attend, home-based services are provided.

All ages. Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies (US) and to support parents in maximizing quality of life. Some issues to consider:

  • IEP services:
    • An IEP provides specially designed instruction and related services to children who qualify.
    • IEP services will be reviewed annually to determine whether any changes are needed.
    • Special education law requires that children participating in an IEP be in the least restrictive environment feasible at school and included in general education as much as possible, when and where appropriate.
    • Vision and hearing consultants should be a part of the child's IEP team to support access to academic material.
    • PT, OT, and speech services will be provided in the IEP to the extent that the need affects the child's access to academic material. Beyond that, private supportive therapies based on the affected individual's needs may be considered. Specific recommendations regarding type of therapy can be made by a developmental pediatrician.
    • As a child enters the teen years, a transition plan should be discussed and incorporated in the IEP. For those receiving IEP services, the public school district is required to provide services until age 21.
  • A 504 plan (Section 504: a US federal statute that prohibits discrimination based on disability) can be considered for those who require accommodations or modifications such as front-of-class seating, assistive technology devices, classroom scribes, extra time between classes, modified assignments, and enlarged text.
  • Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a US public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities.
  • Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability.

Motor Dysfunction

Gross motor dysfunction

  • Physical therapy is recommended to maximize mobility and to reduce the risk for later-onset orthopedic complications (e.g., contractures, scoliosis, hip dislocation).
  • Consider use of durable medical equipment and positioning devices as needed (e.g., wheelchairs, walkers, bath chairs, orthotics, adaptive strollers).
  • For muscle tone abnormalities including hypertonia or dystonia, consider involving appropriate specialists to aid in management of baclofen, tizanidine, Botox®, anti-parkinsonian medications, or orthopedic procedures.

Fine motor dysfunction. Occupational therapy is recommended for difficulty with fine motor skills that affect adaptive function such as feeding, grooming, dressing, and writing.

Oral motor dysfunction should be assessed at each visit and clinical feeding evaluations and/or radiographic swallowing studies should be obtained for choking/gagging during feeds, poor weight gain, frequent respiratory illnesses, or feeding refusal that is not otherwise explained. Assuming that the child is safe to eat by mouth, feeding therapy (typically from an occupational or speech therapist) is recommended to help improve coordination or sensory-related feeding issues. Feeds can be thickened or chilled for safety. When feeding dysfunction is severe, an NG-tube or G-tube may be necessary.

Speech, language, and communication issues. Speech-language evaluation should be considered early in development for children who have delayed communication milestones or who are not yet talking. Evaluation for alternative means of communication (e.g., augmentative and alternative communication [AAC]) is appropriate for individuals who have speech or receptive and expressive language difficulties. An AAC evaluation should be completed by a speech-language pathologist who has expertise in the area. This evaluation typically takes into account cognitive abilities, sensory impairments, and motor skills to determine the most appropriate form of communication. AAC devices can range from low-tech, such as picture exchange communication, to high-tech, such as voice-generating devices. Contrary to popular belief, AAC devices do not hinder verbal development of speech, but rather support optimal speech and language development. Many children will continue to require AAC into later childhood and adulthood, while some may use their AAC for a shorter time to help aid speech and language development.

Neurobehavioral Concerns

Consultation with a developmental pediatrician may be helpful in guiding parents through appropriate behavior management strategies or providing prescription medications, such as medication used to treat attention-deficit/hyperactivity disorder, when necessary.

Surveillance

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in Table 6 are recommended.

Table 6.

FGD1-Related Faciogenital Dysplasia (Aarskog-Scott Syndrome): Recommended Surveillance

System/ConcernEvaluationFrequency
Growth/Endocrine Measurement of growth parametersAt every visit until adulthood
Musculoskeletal Clinical examAnnually or as clinically indicated
Urogenital Monitor testicular descent.At each pediatric visit
Dental Dental evalStarting at tooth eruption, then annually or as clinically indicated
Development Monitor developmental progress, educational needs, & for ADHD.At each visit
Eye Ophthalmology evalAnnually in childhood & adolescence or as clinically indicated
Gastrointestinal Assess for inguinal hernia.At each visit
Cardiovascular EchocardiographyAs indicated per cardiologist
ENT Cleft team follow upAs clinically indicated
Audiology evalAnnually in childhood & adolescence or as clinically indicated

ADHD = attention-deficit/hyperactivity disorder; ENT = otolaryngology

Agents/Circumstances to Avoid

Avoid movements that cause sudden stress to the head and neck (e.g., somersaults, head dives, high-force cervical manipulation) and neck hyperextension during procedures until cervical abnormalities have been ruled out. Obtain cervical spine radiographs before general anesthesia.

Evaluation of Relatives at Risk

It is appropriate to clarify the genetic status of apparently asymptomatic older and younger at-risk male relatives of an affected individual in order to identify as early as possible those who would benefit from echocardiogram and management of congenital heart disease.

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members; it is not meant to address all personal, cultural, or ethical issues that may arise or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

FGD1-related faciogenital dysplasia (Aarskog-Scott syndrome) is inherited in an X-linked manner.

Risk to Family Members

Parents of a male proband

  • The father of an affected male will not have the disorder nor will he be hemizygous for the FGD1 pathogenic variant; therefore, he does not require further evaluation/testing.
  • In a family with more than one affected individual, the mother of an affected male is an obligate heterozygote. Note: If a woman has more than one affected child and no other affected relatives and if the FGD1 pathogenic variant cannot be detected in her leukocyte DNA, she most likely has gonadal mosaicism.
  • If a male is the only affected family member (i.e., a simplex case), the mother may be a heterozygote, the affected male may have a de novo FGD1 pathogenic variant (in which case the mother is not a heterozygote), or the mother may have somatic/gonadal mosaicism. Note: Testing of maternal leukocyte DNA may not detect all instances of somatic mosaicism and will not detect a pathogenic variant that is present in the germ (gonadal) cells only.
  • About 10% of affected males have the disorder as the result of a de novo pathogenic variant [Jeanne et al 2025].
  • Molecular genetic testing of the mother is recommended to confirm her genetic status and allow reliable recurrence risk assessment.

Sibs of a male proband. The risk to sibs depends on the genetic status of the mother:

Offspring of a male proband. Affected males transmit the FGD1 pathogenic variant to all of their daughters and none of their sons.

Other family members. The maternal aunts and maternal cousins of a male proband may be at risk of having an FGD1 pathogenic variant.

Note: Molecular genetic testing may be able to identify the family member in whom a de novo pathogenic variant arose, information that could help determine genetic risk status of the extended family.

Heterozygote Detection

Identification of female heterozygotes requires prior identification of the FGD1 pathogenic variant in the family.

Note: Females who are heterozygous for this X-linked disorder will usually be asymptomatic or have a partial, milder phenotype (see Clinical Description, Heterozygous Females).

Related Genetic Counseling Issues

Family planning

  • The optimal time for determination of genetic risk and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy.
  • It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are at risk of having an FGD1 pathogenic variant.

Prenatal Testing and Preimplantation Genetic Testing

Once the FGD1 pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.

Differences in perspective may exist among medical professionals and within families regarding the use of prenatal and preimplantation genetic testing. While most health care professionals would consider use of prenatal and preimplantation genetic testing to be a personal decision, discussion of these issues may be helpful.

Resources

GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A.

FGD1-Related Faciogenital Dysplasia (Aarskog-Scott Syndrome): Genes and Databases

GeneChromosome LocusProteinLocus-Specific DatabasesHGMDClinVar
FGD1 Xp11​.22 FYVE, RhoGEF and PH domain-containing protein 1 FGD1 @ LOVD FGD1 FGD1

Data are compiled from the following standard references: gene from HGNC; chromosome locus from OMIM; protein from UniProt. For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click here.

Table B.

OMIM Entries for FGD1-Related Faciogenital Dysplasia (Aarskog-Scott Syndrome) (View All in OMIM)

300546FYVE, RhoGEF, AND PH DOMAIN-CONTAINING PROTEIN 1; FGD1
305400AARSKOG-SCOTT SYNDROME; AAS

Molecular Pathogenesis

FGD1 encodes a guanine-nucleotide exchange factor that activates rho-GTPase CDC42 [Genot et al 2012]. The FGD1 protein localizes to the Golgi and subcortical actin network, where it coordinates post-Golgi trafficking and cytoskeletal dynamics, especially in osteogenic tissues. FGD1 pathogenic variants reduce CDC42 activation, leading to a defective trafficking from the Golgi and perturbed actin-microtubule organization. These defects can be partly rescued by constitutively active CDC42 or by engaging Golgi CDC42 effectors (PAK1, IQGAP1, N-WASP, PAR6) [Egorov & Polishchuk 2019].

Mechanism of disease causation. Loss of function

Chapter Notes

Author Notes

Dr Médéric Jeanne (rf.nartse-hc@ennaej.m) is actively involved in clinical research regarding individuals with Aarskog-Scott syndrome. He would be happy to communicate with persons who have any questions regarding diagnosis of Aarskog-Scott syndrome or other considerations. Contact Dr Jeanne to inquire about review of FGD1 variants of uncertain significance.

Acknowledgments

The author is sincerely grateful to the patients and families whom the author has had the privilege to meet and follow in clinic, and to those who generously contributed to research by sharing clinical data and samples. The author also thanks all collaborators across the participating centers.

Revision History

  • 12 February 2026 (sw) Review posted live
  • 2 September 2025 (mj) Original submission

References

Literature Cited

  • Al-Semari A, Wakil SM, Al-Muhaizea MA, Dababo M, Al-Amr R, Alkuraya F, Meyer BF. Novel FGD1 mutation underlying Aarskog-Scott syndrome with myopathy and distal arthropathy. Clin Dysmorphol. 2013;22:13-7. [PubMed: 23211637]
  • Aten E, Sun Y, Almomani R, Santen GW, Messemaker T, Maas SM, Breuning MH, den Dunnen JT. Exome sequencing identifies a branch point variant in Aarskog-Scott syndrome. Hum Mutat. 2013;34:430-4. [PubMed: 23169394]
  • Bayat A, Krett B, Dunø M, Torring PM, Vissing J. Novel truncating variants in FGD1 detected in two Danish families with Aarskog-Scott syndrome and myopathic features. Am J Med Genet A. 2022;188:2251-7. [PMC free article: PMC9321604] [PubMed: 35388608]
  • Bottani A, Orrico A, Galli L, Karam O, Haenggeli CA, Ferey S, Conrad B. 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;143A:2334-8. [PubMed: 17847065]
  • Caughey AB, Krist AH, Wolff TA, Barry MJ, Henderson JT, Owens DK, Davidson KW, Simon MA, Mangione CM. USPSTF approach to addressing sex and gender when making recommendations for clinical preventive services. JAMA. 2021;326:1953-61. [PubMed: 34694343]
  • Depeyre A, Schlund M, Gryseleyn R, Ferri J. Dental and maxillofacial signs in Aarskog syndrome: a review of 3 siblings and the literature. J Oral Maxillofac Surg. 2018;76:2202-8. [PubMed: 29689188]
  • Egorov M, Polishchuk R. Identification of CDC42 effectors operating in FGD1-dependent trafficking at the Golgi. Front Cell Dev Biol. 2019;7:7. [PMC free article: PMC6369352] [PubMed: 30778386]
  • Fryns JP. Aarskog syndrome: the changing phenotype with age. Am J Med Genet. 1992 Apr 15;43:420-7. [PubMed: 1605221]
  • Genot E, Daubon T, Sorrentino V, Buccione R. FGD1 as a central regulator of extracellular matrix remodelling--lessons from faciogenital dysplasia. J Cell Sci. 2012;125:3265-70. [PubMed: 22854039]
  • Griffin LB, Farley FA, Antonellis A, Keegan CE. A novel FGD1 mutation in a family with Aarskog-Scott syndrome and predominant features of congenital joint contractures. Cold Spring Harb Mol Case Stud. 2016;2:a000943. [PMC free article: PMC4990810] [PubMed: 27551683]
  • Jeanne M, Ronce N, Remize S, Arpin S, Baujat G, Breton S, Petit F, Vanlerberghe C, Coeslier-Dieux A, Manouvrier-Hanu S, Vincent-Delorme C, Khau Van Kien P, Van-Gils J, Quelin C, Pasquier L, Odent S, Demurger F, Laffargue F, Francannet C, Martin-Coignard D, Afenjar A, Whalen S, Verloes A, Capri Y, Delahaye A, Plaisancie J, Labrune P, Destree A, Maystadt I, Ciorna Monferrato V, Isidor B, Vincent M, Jean Marcais N, Nambot S, Schaefer E, El Chehadeh S, Lespinasse J, Collignon P, Busa T, Philip N, Willems M, Planes M, Vanakker OM, Lambert L, Leheup B, Mathieu-Dramard M, Morin G, Dieterich K, Ginglinger E, Bayat A, Balasubramanian M, Dauriat B, Haye D, Amiel J, Rio M, Cormier-Daire V, Toutain A. Aarskog-Scott syndrome: a clinical study based on a large series of 111 male patients with a pathogenic variant in FGD1 and management recommendations. J Med Genet. 2025;62:258-67. [PubMed: 39798962]
  • Lizcano-Gil LA, Garcia-Cruz D, Cantu JM, Fryns JP. The facio-digito-genital syndrome (Aarskog syndrome): a further delineation of the distinct radiological findings. Genet Couns. 1994;5:387-92. [PubMed: 7888143]
  • Manickam K, McClain MR, Demmer LA, Biswas S, Kearney HM, Malinowski J, Massingham LJ, Miller D, Yu TW, Hisama FM, et al. Exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability: an evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2021;23:2029-37. [PubMed: 34211152]
  • Orrico A, Galli L, Cavaliere ML, Garavelli L, Fryns JP, Crushell E, Rinaldi MM, Medeira A, Sorrentino V. Phenotypic and molecular characterisation of the Aarskog-Scott syndrome: a survey of the clinical variability in light of FGD1 mutation analysis in 46 patients. Eur J Hum Genet. 2004;12:16-23. [PubMed: 14560308]
  • Orrico A, Galli L, Clayton-Smith J, Fryns JP. Clinical utility gene card for: Aarskog-Scott Syndrome (faciogenital dysplasia) - update 2015. Eur J Hum Genet. 2015;23. [PMC free article: PMC4667502] [PubMed: 25227149]
  • Orrico A, Galli L, Faivre L, Clayton-Smith J, Azzarello-Burri SM, Hertz JM, Jacquemont S, Taurisano R, Arroyo Carrera I, Tarantino E, Devriendt K, Melis D, Thelle T, Meinhardt U, Sorrentino V. Aarskog-Scott syndrome: clinical update and report of nine novel mutations of the FGD1 gene. Am J Med Genet A. 2010;152A:313-8. [PubMed: 20082460]
  • Pavone P, Marino S, Maniaci A, Cocuzza S. Aarskog-Scott syndrome: clinical and molecular characterisation of a family with the coexistence of a novel FGD1 mutation and 16p13.11-p12.3 microduplication. BMJ Case Rep. 2020;13:e235183. [PMC free article: PMC7328892] [PubMed: 32606125]
  • Pilozzi-Edmonds L, Maher TA, Basran RK, Milunsky A, Al-Thihli K, Braverman NE, Alfares A. Fraternal twins with Aarskog-Scott syndrome due to maternal germline mosaicism. Am J Med Genet A. 2011;155A:1987-90. [PubMed: 21739585]
  • Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405-24. [PMC free article: PMC4544753] [PubMed: 25741868]
  • Rodan LH, Stoler J, Chen E, Geleske T; Council on Genetics. Genetic evaluation of the child with intellectual disability or global developmental delay: clinical report. Pediatrics. 2025;156:e2025072219. [PubMed: 40545261]
  • Satoh M, Yokoya S. Anabolic steroid and gonadotropin releasing hormone analog combined treatment increased pubertal height gain and adult height in two children who entered puberty with short stature. J Pediatr Endocrinol Metab. 2006;19:1125-31. [PubMed: 17128560]
  • Stenson PD, Mort M, Ball EV, Chapman M, Evans K, Azevedo L, Hayden M, Heywood S, Millar DS, Phillips AD, Cooper DN. The Human Gene Mutation Database (HGMD®): optimizing its use in a clinical diagnostic or research setting. Hum Genet. 2020;139:1197-207. [PMC free article: PMC7497289] [PubMed: 32596782]
  • Verhoeven WM, Egger JI, Hoogeboom AJ. X-linked Aarskog syndrome: report on a novel FGD1 gene mutation. Executive dysfunction as part of the behavioural phenotype. Genet Couns. 2012;23:157-67. [PubMed: 22876573]
  • Zanetti Drumond V, Sousa Salgado L, Sousa Salgado C, Oliveira VAL, de Assis EM, Campos Ribeiro M, Furtado Valadão A, Orrico A. The prevalence of clinical features in patients with Aarskog-Scott syndrome and assessment of genotype-phenotype correlation: a systematic review. Genet Res (Camb). 2021;2021:6652957. [PMC free article: PMC7953535] [PubMed: 33762894]
Copyright © 1993-2026, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright (© 1993-2026 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

Bookshelf ID: NBK620763PMID: 41704117
GeneReviews by Title

Views

In this GeneReview

Bulk Download

GeneReviews Links

Tests in GTR by Gene

Related information

  • OMIM
    Related OMIM records
  • PMC
    PubMed Central citations
  • PubMed
    Links to PubMed
  • Gene
    Locus Links

Similar articles in PubMed

See reviews...See all...

Recent Activity

ClearTurn OffTurn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...