Faciogenital dysplasia (FGDY) was first described by Aarskog in 1970 as a familial syndrome of short stature asso- ciated with facial and genital anomalies. The occurrence of ligamentous laxity was emphasized by Scott in 1971. The syn- drome is also known as Aarskog syndrome, Aarskog-Scott syndrome, and facio-digito-genital syndrome.
GENETICS/BASIC DEFECTS
1. Inheritance
a. X-linked recessive inheritance with occasional partial expression in the heterozygote
b. Caused by mutations in the FGDY gene (FGDY1) affecting multiple skeletal structures including cranio- facial bones, vertebrae, ribs, long bones, and phalanges 2. The FGDY1 gene
a. Mapped to the pericentromeric region of the X chro- mosome by the observation of an X;8 translocation in an affected mother and son (breakpoint at Xp11.21) b. Encoding a guanine nucleotide exchange factor that
specifically activates the P21 GTPase Cdc42, a member of the Rho (Ras homology) family of GTPase proteins
CLINICAL FEATURES
1. Typical triad of the syndrome a. Facial appearance
i. Rounded facies
ii. Prominent metopic ridge iii. Widow’s peak hair anomaly
iv. Ocular hypertelorism v. Ptosis
vi. Antimongoloid obliquity of palpebral fissures vii. Small & short nose
viii. Anteverted nares ix. Broad nasal bridge
x. Broad long philtrum
xi. Maxillary and mandibular hypoplasia xii. Slight crease below lower lip
xiii. Low-set ears with fleshy earlobes and incom- plete outfolding of upper helices
b. Digital anomalies i. Hands
a) Short and broad hands b) Hypermobility of fingers
c) Cutaneous syndactyly (interdigital webbing) d) Clinodactyly with hypoplasia of middle pha-
langes
e) Transverse palmar crease ii. Feet
a) Short and broad feet b) Bulbous toes c) Metatarsus varus
d) Hypoplasia of the middle or terminal phalanges
c. Genital abnormalities
i. Shawl scrotum (scrotal folds encircling the base of the penis)
ii. Cryptorchidism iii. Phimosis
iv. Hypoplasia v. Renal hypoplasia 2. Growth
a. Failure to thrive b. Delayed puberty
c. Slight to moderate (disproportionate acromelic) short stature (71%)
3. Intelligence and behavioral disorders
a. Most individuals with normal intelligence: hyperac- tive and attention deficits present in 61% of these indi- viduals, which usually regress after 12–14 years of age b. Individuals with subnormal to mentally retarded (30%): hyperactive and attention deficits present in 84% of these individuals
4. Dental abnormalities a. Hypodontia
b. Retarded dental eruption c. Orthodontic problems 5. Ocular features
a. Strabismus b. Nystagmus c. Amblyopia
d. Bilateral blepharoptosis e. Astigmatism
f. Hyperopia g. Anisometropia h. Corneal enlargement
i. Deficient ocular elevation j. Blue sclera
k. Posterior embryotoxon l. Ophthalmoplegia
m. Tortuosity of the retinal vessels 6. Musculoskeletal anomalies
a. Cervical vertebral anomalies b. Spina bifida occulta
c. Mild pectus excavatum d. Genu recurvatum e. Joint restriction
f. Prominent umbilicus g. Inguinal hernias 7. Other rare signs
a. Gastrointestinal obstruction and volvulus in a few patients
b. Rare perinatal occurrence of severe cerebrovascular accidents
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372 FACIOGENITAL (AARSKOG) DYSPLASIA
8. Clinical variability and changing phenotype with age 9. Carrier females often present with minor manifestations
of disorder, especially relatively short stature and subtle craniofacial anomalies
DIAGNOSTIC INVESTIGATIONS
1. Ophthalmic examination 2. Radiography
a. Ocular hypertelorism
b. Short tubular bones with widened metaphysis c. Brachydactyly
d. Clinodactyly of 5th fingers e. Hypoplastic middle phalanges
f. Mild interdigital webbing g. Cubitus valgus
h. Splayed toes with bulbous tips i. Metatarsus adductus
j. Broad flat feet
k. Cervical vertebral anomalies i. Odontoid hypoplasia ii. Fused cervical vertebrae iii. Spina bifida occulta l. Scoliosis
m. Additional pairs of ribs n. Retarded bone age
3. Mutation analysis: available clinically by sequencing the entire coding region of FGD1 gene
GENETIC COUNSELING
1. Recurrence risk
a. Patient’s sib: 50% risk of having affected brothers if the mother is a carrier; otherwise recurrence risk not increased
b. Patient’s offspring: 50% of his daughters to be carri- ers; no increased risk to his sons
2. Prenatal diagnosis by ultrasonography: possible with a positive family history of a previously affected child by demonstrating ocular hypertelorism, short long bones, vertebral defects, and digital anomalies in a male fetus a. Ultrasonography: possible with a positive family his-
tory of a previously affected child by demonstrating ocular hypertelorism, short long bones, vertebral defects, and digital anomalies in a male fetus b. Mutation analysis of FGD1 gene on fetal DNA
obtained from amniocytes or CVS, provided the mutation has been identified in the proband
3. Management
a. Supportive management
b. Ophthalmological evaluation of the ocular problems for treatable causes of visual loss
c. Surgery for cryptorchidism and inguinal hernia d. Reports of growth hormone treatment indicate a posi-
tive effect on growth and adult height in treated patients
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Fig. 1. Two patients (top 2 photos are same patient) with faciogenital dysplasia showing short stature, round face, broad forehead, hyper- telorism, mild ptosis, short nose with anteverted nostrils, long philtrum, low-set ears, and broad hands with webbing of fingers.
Fig. 2. Shawl scrotum of a patient with faciogenital dysplasia.
