Aarskog-Scott syndrome (ORPHA:915)
A rare developmental disorder characterized by facial, limbs and genital features, and a disproportionate acromelic short stature.
Epidemiology
AAS prevalence is not known, but less than 100 cases have been reported in the literature since the first description in 1970. However, prevalence estimates are thought to be around 1/25,000. About 40 molecularly proven cases are published worldwide.
Clinical description
AAS predominantly concerns males. Facial features include widow's peak and hypertelorism, both observed in female carriers, and downslanting palpebral fissures, broad nasal bridge, anteversed nostrils, low set and protuberant ears, maxillary hypoplasia and transverse crease below the lower lip. AAS patients have short and broad hands and feet, interdigital webbing, clinodactyly, and hyperextension of proximal interphalangeal joints and flexion at distal interphalangeal joints causing swan neck deformity of fingers. Size is generally normal at birth, but growth is slow in infancy and childhood, leading to short stature until puberty, which is often delayed. A growth spurt in late teens, generally, results in a moderate short stature. Genital anomalies may include cryptorchidism, macroorchidism, shawl scrotum and, more rarely, hypospadias. Fertility is normal. Female carriers may have only a subtle phenotype with hypertelorism and widow's peak. Patients may present a neurodevelopmental phenotype with learning and behavioural disabilities that are often confined to early childhood. When present, mental impairment is rarely severe.
Etiology
Although clinically and genetically heterogeneous, the best characterized form of the disorder is caused by mutations in the FGD1 gene (faciogenital dysplasia 1 gene; Xp11.21). Other gene(s) might be involved since most familial cases still do not have identified genetic cause.
Diagnostic methods
Clinical diagnosis is based on physical examination and the recognition of the most distinctive clinical hallmarks. Molecular genetics, based on analysis of the FGD1 gene, may confirm diagnosis.
Differential diagnosis
When molecular diagnosis is not conclusive, all possible options for differential diagnosis should still be considered, including Noonan syndrome, SHORT syndrome, pseudohypoparathyroidism and Robinow syndrome (see these terms).
Antenatal diagnosis
Prenatal diagnosis for pregnancies at increased risk is technically possible when the disease-causing mutation in the family is known (the majority of mutations are family specific). However, prenatal testing is unlikely to be requested frequently, because usually physical signs can be mild and the clinical heterogeneity makes difficult a prediction of the phenotype, even within the same family.
Genetic counseling
AAS is an X-linked disease, but autosomal dominant and autosomal recessive transmissions have also been reported. Genetic counseling thus requires in depth investigation of patient's family history.
Management and treatment
There is no curative treatment for AAS. Preliminary results of growth hormone administration in childhood do not seem to show a significant effect. Learning problems and attention deficit and hyperactivity disorder (ADHD), in case, may require a neuropsychiatric intervention.
Prognosis
The majority of patients present a good prognosis. Typically, they have a good evolution into adulthood with an age-related improvement of mental status.

                            Last update: 
                            October 2012


                            - Expert reviewer(s): 
                            Dr Alfredo ORRICO