Aarskog syndrome is a rare genetic condition characterized by short stature and multiple facial, limb and genital abnormalities. Additionally, some types of cognitive disorders may occasionally be present. Up to now, the FGD1 gene on the X chromosome is the only gene known to be associated with Aarskog syndrome.

Aarskog-Scott syndrome, also known as facial and genital dysplasia, is an X-linked disorder characterized by short stature, hypertelorism, shawl scrotum, and brachydactyly, although there is wide phenotypic variability and other features, such as joint hyperextensibility, short nose, widow’s peak, and inguinal hernia, may also occur. Most patients do not have mental retardation, but some may have neurobehavioral features. Carrier females may present with subtle features, such as widow’s peak or short stature.

These are few other names of Aarskog syndrome

  • Aarskog syndrome
  • AAS
  • facio-digito-genital dysplasia
  • faciodigitogenital syndrome
  • faciogenital dysplasia
  • FGDY
  • Aarskog disease
  • Aarskog-Scott syndrome
  • Scott Aarskog syndrome

Signs & Symptoms of Aarskog syndrome

Aarskog syndrome primarily affects males. Affected boys exhibit a characteristic set of facial, skeletal, and genital abnormalities. Clinical signs may vary from person to person (clinical heterogeneity), even within families. Males with Aarskog syndrome often have a rounded face with a broad forehead. Additional characteristic facial features include widely spaced eyes (ocular hypertelorism), drooping (ptosis) of the eyelids, downwardly slanting eyelid folds (palpebral fissures), a small nose with nostrils that are flared forward (anteverted nares), an underdeveloped upper jawbone (maxillary hypoplasia), and a widow’s peak. Affected individuals may also have an abnormally long groove in the upper lip (philtrum) and a broad nasal bridge.

Most males with Aarskog-Scott syndrome have a shawl scrotum, in which the scrotum surrounds the penis instead of hanging below. Less often, they have undescended testes (cryptorchidism) or a soft out-pouching around the belly-button (an umbilical hernia) or in the lower abdomen (an inguinal hernia).

The intellectual development of people with Aarskog-Scott syndrome varies widely. Some may have mild learning and behavior problems, while others have normal intelligence. In rare cases, severe intellectual disability has been reported.

These children may also have a variety of abnormalities affecting the ears and teeth. Ear abnormalities include low-set ears and thickened, “fleshy” earlobes. Dental abnormalities include missing teeth at birth, delayed eruption of teeth, and underdevelopment of the hard outer covering of teeth (enamel hypoplasia).

Everything you should know about Aarskog syndrome
Everything you should know about Aarskog syndrome

Aarskog syndrome is basically a skeletal dysplasia and affected males develop characteristic malformations of the skeletal system including disproportionate short stature; broad, short hands and feet; short, stubby fingers (brachydactyly) with permanent fixation of the fifth fingers in a bent position (clinodactyly); abnormally extendible finger joints; and wide flat feet with bulbous toes. In addition, affected individuals may have a sunken chest (pectus excavatum), protrusion of portions of the large intestine through an abnormal opening in the muscular lining of the abdominal cavity (an inguinal hernia), and a prominent navel (umbilicus). Individuals with Aarskog syndrome may have spinal abnormalities such as incomplete closure of the bones of the spinal column (spina bifida occulta), a fusion of the upper bones of the spinal column (cervical vertebrae), and underdevelopment of the “peg-like” projection of the second cervical vertebra (odontoid hypoplasia).

A sign that helps to make a diagnosis in males with Aarskog syndrome is the genital abnormalities, including a characteristic abnormal fold of skin extending around the base of the penis (“shawl” scrotum) and/or failure of one or both of the testes to descend into the scrotum (cryptorchidism). In addition, the urinary opening (meatus) may be located on the underside of the penis (hypospadias) and the scrotum may appear cleft or divided (bifid scrotum).

Intellectual disability has been described in some affected boys but it is not a consistent feature of the disorder. Affected individuals may present with a range of mild learning difficulty and/or behavioral disorders: affected children may exhibit developmental delay during infancy, hyperactivity, attention deficit, impulsivity, and opposition. Failure to gain weight and grow at the expected rate (failure to thrive) and development of chronic respiratory infections have also been described.

An additional spectrum of signs and/or symptoms may occur less frequently, including congenital heart defects; abnormal side-to-side curvature of the spine (scoliosis); additional pairs of ribs; incomplete closure of the roof of the mouth (cleft palate) and/or a vertical groove in the upper lip (cleft lip); mild webbing of the fingers; and a short neck with or without webbing. Additional eye abnormalities may be present including crossed eyes (strabismus), farsightedness (hyperopia), and paralysis of certain eye muscles (ophthalmoplegia).

Details about Aarskog-Scott syndrome Inheritance pattern

When caused by FGD1 gene mutations, Aarskog-Scott syndrome is inherited in an X-linked recessive pattern. The FGD1 gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause Aarskog-Scott syndrome. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. Females who carry one altered copy of the FGD1 gene may show mild signs of the condition, such as hypertelorism, short stature, or a widow’s peak hairline. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Evidence suggests that Aarskog-Scott syndrome is inherited in an autosomal dominant or autosomal recessive pattern in some families, although the genetic cause of these cases is unknown. In autosomal dominant inheritance, one copy of the altered gene in each cell is sufficient to cause the disorder. In autosomal recessive inheritance, both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

What are Genetic Changes you can see in Aarskog-Scott syndrome

Mutations in the FGD1 gene are the only known genetic cause of Aarskog-Scott syndrome. The FGD1 gene provides instructions for making a protein that turns on (activates) another protein called Cdc42, which transmits signals that are important for various aspects of development before and after birth.

Mutations in the FGD1 gene lead to the production of an abnormally functioning protein. These mutations disrupt Cdc42 signaling, leading to the wide variety of abnormalities that occur in people with Aarskog-Scott syndrome.

Only about 20 percent of people with this disorder have identifiable mutations in the FGD1 gene. The cause of Aarskog-Scott syndrome in other affected individuals is unknown.

Estimated population prevalence of Aarskog syndrome

Approximately 50 reports of Aarskog syndrome confirmed by identification of an FGD1 gene mutation have been published worldwide. However, it is possible that some mildly affected children may be unrecognized, making it difficult to determine the true frequency of this condition in the general population. An estimated population prevalence of Aarskog syndrome is equal to or slightly lower than to 1/25,000.

Differential Diagnosis of Aarskog syndrome

Differential Diagnosis of Aarskog syndrome can be done with the following syndromes or Disorders. you can see details About these Disorders or syndromes on other posts.

  • Noonan syndrome
  • Robinow syndrome
  • LEOPARD Syndrome

How to Diagnose Aarskog syndrome

Molecular Genetics Tests

  • Sequence analysis of the entire coding region
  • Detection of homozygosity
  • Linkage analysis
  • Sequence analysis of select exons
  • Deletion/duplication analysis
  • Targeted variant analysis

A diagnosis of Aarskog syndrome may be considered based upon a thorough clinical evaluation, a detailed patient and family history, and the identification of characteristic findings. Molecular genetic testing for FGD1 gene mutations is available to confirm the diagnosis. If an FGD1 gene mutation is not identified, molecular genetic testing for genes associated with similar conditions may be suggested, such as the ROR2 and WNT5Agenes associated with Robinow syndrome.

Associated Genes with Aarskog syndrome

FGD1 is Also known as AAS, FGDY, MRXS16, ZFYVE3, FGD1

Everything you should know about Aarskog syndrome
Everything you should know about Aarskog syndrome

Clinical Features of Aarskog syndrome

  • Abnormality of connective tissue
    Inguinal hernia
  • Abnormality of head or neck
    Anteverted nares
    Broad philtrum
    Cleft secondary palate
    Cleft upper lip
    Curved linear dimple below the lower lip
    down-slanted palpebral fissures
    Hypoplasia of the maxilla
    Partial congenital absence of teeth
    Round face
    Short neck
    Wide nasal bridge
    Widow peak
  • Abnormality of limbs
    Broad foot
    Broad palm
    Hyperextensibility of the finger joints
    Radial deviation of finger
    Short foot
    Short palm
    Single transverse palmar crease
  • Abnormality of the digestive system
    Inguinal hernia
    Prominent umbilicus
  • Abnormality of the endocrine system
    Delayed female puberty
  • Abnormality of the genitourinary system
    Cryptorchidism, unilateral or bilateral
    Shawl scrotum
  • Abnormality of the genitourinary system
    Cryptorchidism, unilateral or bilateral
    Decreased fertility
    Shawl scrotum
  • Abnormality of the integument
    Single transverse palmar crease
    Widow peak
  • Abnormality of the nervous system
    Attention deficit hyperactivity disorder
    Intellectual disability
  • Abnormality of the skeletal system
    Cervical spine hypermobility
    Hyperextensibility of the finger joints
    Hypoplasia of the maxilla
    Odontoid hypoplasia
    Pectus excavatum
    Radial deviation of finger
    Short foot
    Short neck
    Short palm
  • Congenital anomaly of eye
  • Disorder of endocrine system
    Delayed female puberty
  • Ear malformation
    Large earlobe
  • Growth abnormality
    Delayed female puberty
    Failure to thrive
    Increased upper to lower segment ratio
    Mild short stature

Possible Complications of Aarskog syndrome

These complications can occur:

  • Changes in the brain
  • Difficulty growing in the first year of life
  • Poorly aligned teeth
  • Seizures
  • Undescended testicles

How to treat or manage Aarskog syndrome

The treatment of Aarskog syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, surgeons, cardiologists, dental specialists, speech pathologists, specialists who assess and treat hearing problems (audiologists), eye specialists, and other healthcare professionals may need to systematically and comprehensively plan an affected child’s treatment.

Moving the teeth may be done to treat some of the abnormal facial features a person with Aarskog syndrome may have.

Surgery may be necessary to treat specific congenital or structural malformations sometimes associated with Aarskog syndrome (hypospadias, inguinal or umbilical hernias, cryptorchidism, unusually severe craniofacial features). Individuals with Aarskog syndrome should receive complete eye and dental evaluations. Growth hormone treatment has been reported to improve height in some children, but confirmation is needed to determine appropriate management and expectations for response. For the possibly neurodevelopmental symptoms, a neuropsychiatric evaluation and input may be indicated. Another treatment is symptomatic and supportive.

Genetic counseling is recommended for affected individuals and their families to clarify the genetic and clinical characteristics, the inheritance, and the recurrence risks of the condition in their families.

When to Contact a Medical Professional in case of Aarskog syndrome

Call your health care provider if your child has delayed growth or if you notice any symptoms of Aarskog syndrome. Seek genetic counseling if you have a family history of Aarskog syndrome. Contact a genetic specialist if your provider thinks you or your child may have Aarskog syndrome.

For More Information: https://en.wikipedia.org/wiki/Aarskog%E2%80%93Scott_syndrome


Please enter your comment!
Please enter your name here