Aarskog-Scott Syndrome - An Overview

What Is Aarskog-Scott Syndrome?

Aarskog-Scott syndrome, also known as a facio-digital-genital syndrome, is a very rare, X-linked autosomal genetic disorder, particularly affecting males, characterized by multiple facial, muscular, skeletal, and genital abnormalities.

What Are the Other Synonyms?

• Aarskog disease.

• Aarskog syndrome.

• Faciodigitogenital syndrome.

• Faciogenital dysplasia.

What Is the Prevalence of Aarskog-Scott Syndrome in Society?

Aarskog-Scott syndrome is a very rare disease with an estimated population prevalence of equal to or lower than 1/25,000. However, the mildly affected cases cannot be diagnosed.

What Is the Cause of Aarskog-Scott Syndrome?

Genetic Mutations:

• Aarskog syndrome is a hereditary disorder related to the X chromosome. It mainly affects male individuals, but females may also be affected with a milder form. The disorder is mainly caused by genetic mutations in a gene called faciogenital dysplasia (FGD1).

• An abnormally functioning protein is generated because of the mutations in the faciogenital dysplasia gene (FGD1).

• These mutations disrupt Cdc 42 signaling, which in turn leads to a wide variety of anomalies in individuals suffering from Aarskog-Scott syndrome.

• Approximately 20 percent of the population who is suffering from this disorder has known mutations in the FGD1 gene. However, in other affected individuals, the cause remains unknown.

What Are the Signs and Symptoms of Aarskog- Scott Syndrome?

Aarskog–Scott syndrome affects the development of multiple parts of the body of an individual, including the skeleton, muscles, genitals, height, and appearance. People suffering from this condition usually present with the following:

Facial Abnormality:

• Abnormally rounded facial appearance.

• Ocular hypertelorism (widely spaced eyes).

• Ptosis or drooping of the eyelids.

• Eyelids showing palpebral fissures.

• Small nose with upturned nostrils.

• Wide nasal bridge.

• The middle portion of the face is poorly developed.

• Abnormally long groove in the upper lip (philtrum).

• Maxillary hypoplasia (underdeveloped upper jaw).

• Widow’s peak (V-shaped hairline).

• The top portion of the ear folded over slightly with fleshy earlobes.

Muscular Defect:

• Soft pouch around the belly button that sticks out (umbilical hernia).

Genital Defects:

• Inguinal hernia (a part of the intestinal part protrudes through the abdomen).

• The bifid scrotum (midline cleft in the scrotum).

• Delayed sexual maturity.

• The scrotum surrounds the penis instead of hanging below (shawl scrotum).

• Undescended testicles.

Dental Defects:

• Delayed teeth eruption and missing teeth since birth.

• Enamel hypoplasia.

• Cleft lip and cleft palate.

Skeletal Defects:

• Sunken chest.

• Incomplete closure of the bones present in the spinal cord.

• Brain not properly developed, showing intellectual disability.

• Mild to moderate short stature.

• A single crease across the palm of a hand.

• Short, broad hands and feet.

• Webbing of the skin in between some fingers (syndactyly).

• Short fingers with the fifth finger bent in.

• Broad, flat feet with bulbous toes.

Ocular Defects:

• Congenital heart defects have also been reported.

• Crossed eyes (strabismus).

• Farsightedness (a condition in which distant objects are clearly visible but the near objects are blurred).

• Paralysis or ophthalmoplegia of a few eye muscles.

What Are the Radiographic Features of Aarskog- Scott Syndrome?

1. Orthopantomogram (OPG): A patient’s OPG usually reveals the short and blunt roots of mandibular teeth. Unerupted tooth buds can also be seen.

2. Hand-wrist Radiographs: These radiographs demonstrate the fusion of epiphysis and diaphysis of the radius bone. The radiograph also shows a star-like pattern of the digits.

3. Spinal X-Ray: It might show lumbar kyphoscoliosis also.

What Are the Investigations Done for Aarskog-Scott Syndrome?

The following investigations can be carried out:

Genetic Tests:

• Genetic testing or gene mapping to test for the mutations in the FGD1 gene of the affected individual.

• Genetic counseling is indicated for individuals or families who are affected by this disorders.

Imaging Techniques:

• X-rays can demonstrate skeletal abnormalities.

• Orthopantomogram.

• Ultrasonography can be done for prenatal diagnosis if a positive family history of a previously affected child comes into the knowledge of a healthcare professional by demonstrating ocular hypertelorism, short bones, vertebral and skeletal defects, and digital abnormalities in the fetus.

• Ultrasound of the abdomen can be done to look for undescended testis.

• CT scan of the brain to look for cystic development.

Family History of Patient:

• A detailed family history should be taken for a better diagnosis.

Extensive Physical Examination:

• An extensive physical examination to document the morphological and phenotypical features of the affected individual should be undertaken.

Echocardiogram:

• An echocardiogram should be done to screen for any heart abnormalities.

What Is the Differential Diagnosis of the Aarskog-Scott Syndrome?

The differential diagnosis must be investigated carefully since some of the morphological features overlap with other disorders or syndromes that demonstrate similar clinical features. Some of these disorders are:

• Noonan syndrome (a genetic disorder affecting various parts of the body).

• SHORT syndrome (short stature, hyperextensibility of the joints, ocular depression, Rieger anomaly, which is a congenital ocular defect of the iris, and delayed teething).

• Robinow syndrome (a genetic disorder affecting parts of the skeleton).

• Fetal alcohol syndrome (a condition in which a child is exposed to alcohol during the prenatal period because of the mother).

Clinical manifestations such as ocular hypertelorism, short stature or height, genital abnormalities, and ptosis generally overlap among these conditions. Therefore, it is of paramount importance for the clinical practitioner to reaffirm the diagnosis of the individuals affected with Aarskog-Scott Syndrome with genetic testing. Genetic testing is, therefore, a confirmed investigatory procedure to reach the final diagnosis.

What Is the Treatment of Aarskog-Scott Syndrome?

The Aarskog–Scott syndrome cannot be cured, just like other genetic disorders. The therapeutic approach of the Aarskog-Scott syndrome is specifically directed toward the management of the typical symptoms that are clinically apparent in every patient.

Specialized Medical Team:

• A well-coordinated team of specialists which includes pediatricians, surgeons, cardiologists, dental specialists, speech pathologists, ENT (ear, nose, and throat) specialists, and specialists who treat hearing problems (audiologists), eye surgeons, radiologists, healthcare professionals, should be established to plan the treatment of the affected child wisely, systematically and in a proper comprehensive manner.

Surgical Management:

• Surgery may sometimes be essentially required to surgically cure specific congenital or structural defects and malformations that might be associated with individuals affected by Aarskog-Scott syndrome.

• The surgeries can be done for inguinal or umbilical hernias, cryptorchidism, unusually severe and abnormal craniofacial features, or skeletal deformities.

• Individuals affected with Aarskog syndrome should get their complete eye and dental evaluations done thoroughly.

Neurological Evaluation:

• A neuropsychiatric evaluation should be carried out for abnormal neurodevelopmental symptoms, and subsequently, various treatment options may be suggested.

Dental Treatment:

• Orthodontic treatment may be done by the orthodontist to correct some of the facial anomalies.

• Missing teeth can be replaced by the dentist to improve facial appearance.

Growth Hormone Novel Therapy:

• Growth hormone trials are effective in certain affected individuals to treat short stature.

Genetic Counseling:

• Genetic counseling should also be recommended for affected individuals and their families to identify the genetic and phenotypic characteristics, the genetic inheritance within the family, and the subsequent recurrence risks of the disorder in their families.

Conclusion

The Aarskog-Scott syndrome may remain undiagnosed due to the rare nature of the condition. The phenotypic and morphological features are typically characteristic and play a crucial role in the diagnosis of the Aarskog- Scott syndrome. However, it is observed that some individuals may exhibit mental slowness, but children suffering from this condition often have good social skills. A multidisciplinary approach involving pediatricians, orthopedic surgeons, dentists, neuropsychiatrists, ENT specialists, and cardiologists is required for the proper diagnosis and management of such rare syndromes. The elaboration of more molecular studies is suggested for a better understanding of the molecular mechanisms underlying this rare genetic disorder.