Barcelona, Spain

Synonyms

Faciogenital dysplasia (FGDY, OMIM No. 305400),  facio-digito-genital syndrome , Aarskog-Scott syndrome (AAS).

Definition

Aarskog syndrome is a rare, clinically and genetically heterogeneous condition characterized by facial dysmorphic features, short stature, brachydactyly and genital anomalies [8]. It was first described by Aarskog in 1970 [1] and further delineated by Scott [2] in 1971.

Case report

A 33-year-old woman (G2P1) scanned at 20 weeks of pregnancy. The ultrasound diagnosis revealed just small male genital and cryptorchidism with no other anomalies. The karyotype was normal (46 XY). At the third trimester the fetus start a growth retardation. The definitive diagnosis of the Aarskog syndrome was postulated only postnatally. Here are some of the images we obtained.

Images 1, 2. 2D ultrasonography showing small male genital at 20 weeks of gestation.

Images 3, 4. 3D ultrasonography showing small male genital ("shawl" scrotum) at 20 weeks of gestation.

Images 5, 6. Postnatal appearance of the genital ("shawl" scrotum).

Etiology

The X-linked form of Aarskog syndrome has been ascribed to mutations in the FGD1 gene [6]. However, although Aarskog syndrome may be considered as a relatively frequent clinical diagnosis, mutations have been established only in a few patients [8].

Symptoms

Short stature, rounded face, hairline has a "widow"s peak", wide set eyes with droopy eyelids, small nose with nostrils tipped forward [5], underdeveloped mid-portion of the face, wide groove above the upper lip, crease below the lower lip, delayed eruption of teeth, top portion of the ear folded over slightly, small, broad hands and feet with short fingers and in-curving 5th finger, short fingers and toes with mild webbing, simian crease (single) in palm of the hands [3], protruding belly button, inguinal hernias, "shawl" scrotum, undescended testicles, eyes have downward palpebral slant, pectus excavatum (mildly sunken chest), some degree of cognitive impairment may be as high as 30% in the Aarskog syndrome subjects [4].

Diagnosis

The diagnosis of Aarskog syndrome is primarily based on clinical criteria. In typical cases, the phenotype of affected males is characterised by genital anomalies (shawl scrotum, cryptorchidism), short stature, distinct craniofacial abnormalities, brachydactyly with interdigital webbing and joint laxity. A broad range of mild developmental delay or learning difficulty has occasionally reported. Nevertheless, in affected males the phenotype is variable as they may exhibit different combinations of associated features. In general, carrier females may have a milder phenotype than males, showing minor and mild clinical signs, possibly depending on the pattern of the X-chromosome inactivation.
Disease-causing mutations have been identified in only a small number of patients. FDG1 mutations result in a broad spectrum of severity and, in some cases, may express a clinical appearance very different than typically described. Possibly, both the variability of phenotype and the genetic heterogeneity account for a clinical overdiagnosis.
The diagnosis of the X-linked Aarskog syndrome needs to be made with care as the spectrum of clinical signs overlaps with that of many different disease entities and, although the phenotype may be impressive, many alternative diagnoses have to be considered [7].

Treatment

Orthodontic treatment may be attempted for someone of the facial abnormalities. Trials of growth hormone have not been effective to treat short stature in this disorder.

Prognosis

Mild degrees of mental slowness may be present, but affected children usually have good social skills. Some males may exhibit reduced fertility.

Prevention

There is no guaranteed prevention. Prenatal testing may be available in cases where a relative has a known mutation

References

1.   Aarskog D: A familial syndrome of short stature associated with facial dysplasia and genital anomalies. J Pediatrics 1970;77:856-861.

2.   Scott Jr CI: Inusual fascies, joint hypermobility, genital anomaly and short stature. A new dysmorphic syndrome; in Bergsma D, McKusick VA, Konigsmark BW (eds): The clinical delineation of birth defects. Baltimore:Williams and Wilkins, 1971;10:pp240-246

3.   OberiterV, Lovrencic MK, Schmutzer L, Graus O: The Aarskog syndrome. Acta paediatr Scand 1980 Jul; 69(4): 567-70

4.   Logie LJ, Porteous ME. Intelligence and development in Aarskog syndrome. Arch Dis Child. 1998 Oct; 79(4):359-60

5.   Sepulveda W, Dezerega V, Horvath E, Aracena M. Prenatal sonographic diagnosis of Aarskog síndrome. J Ultrasound Med. 1999 Oct; 18(10):707-10

6.   CE Schwartz, G Gillessen-Kaesbach, M May, M Cappa, J Gorski, K Steindl , G Neri. Two novel mutations confirm FDG1 is responsable for the Aarskog syndrome. Eur. J Hum Genet. Nov 2000; 8 (11): 869-74

7.   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 syndrome: a survey of the clinical variability in light of FDG1 mutation análisis in 46 patients. Eur. J Hum Genet. 2004 Jan;12(1):16-23

8.   Orrico A, Galli L, Obregón MG, de Castro Perez MF, Falciani M, Sorrentino V. Unusually severe expresión of craneofacial features in Aarskog-Scott síndrome due to  a novel truncating mutation of the FDG1 gene. Am J Med Genet A. 2007 Jan 1; 143(1):58-63