Introduction

What is aarskog disease?

Aarskog is a rare medical condition caused by mutation(s) that affect the growth and development of various body parts, such as the face, head, reproductive organs, and limbs.

An overview

Deoxyribonucleic acid ( DNA) is present in living organisms and stores genetic information passed on to the next generation. This genetic information is one of the basic needs for a living being to come into existence, function, and develop fully.

This information is found in a particular order or sequence, and whenever any change occurs in the genetic information’s sequence, that process is called a mutation. This prevents the body from developing and functioning normally.

Aarskog syndrome is caused by mutations in a typical gene, FGD1. The FGD1 gene is responsible for the developmental facet before birth. This FGD1 mutation does not allow the patient to grow and show normal development.

It affects AMAB more than the other genders, however, AFAB also experiences a few of the issues related to Aarskog Syndrome.

Aarskog syndrome is named after Dagfin Aarskog, a Norwegian physician, by whom the syndrome under discussion was noticed and reported for the first time in 1970. Abnormalities related to growth were observed in a set of seven AMABs from the same family.

In the following year of Aarskog syndrome’s reporting, Scott, an American medical geneticist, reported a case with more or less the same features in three brothers. 

Many complications are present, such as bones remaining underdeveloped and the final structure being found abnormal, like broadening of the toes, curves, or bends in the fingers. Fusion of the fingers is also found, and a single crease in the palm is associated with Aarskog syndrome.^{1, 2, 3}

Short stature is a medical condition in which a patient’s height is less than the average height of children of the same age group. It is typically found in teens and height growth is so retarded that among the other children, from the same age group and gender, patients lie in the shortest 3-5 percent.⁴

These delays in growth and development (as compared to normal human beings), due to the FGD1 gene,  were noticed further, which means regular people of the same age and gender (without Aarskog syndrome) look normal, and delayed growth is very much evident among the Aarskog syndrome patients.

Aarskog syndrome delays growth and development

A detailed description of all the sufferings an Aarskog syndrome patient experiences is given below.

Holoprosencephaly

It is a brain-related medical condition in which both halves of the brain do not separate properly, from the front side, but rather fuse into each other. This occurs during 3-4 weeks of pregnancy.

One-third of the patients experience lethality within 24 hours of birth, and half of the patient population dies before the completion of 5 months after birth. The proportion of people who reach adulthood is too small when considering the entire patient population.

Numerous brain-related complications are associated with this condition, like an epileptic seizure, and in fact, epilepsy might be without seizures as well; muscle movement might decrease because of lack of signals from the brain; there may be cases of random muscular movement at any specific site, due improper signal exchange between the site and the brain.

One of the most crucial parts of the brain, called the hypothalamus, is not formed in these patients, which leads the patients to many other complications. The patient’s body might not transmit the basic signals, like hunger, thirst, and even body temperature changes; many hormones’ regulation gets disturbed too.⁵

Hydranencephaly

This medical condition starts coming into play from the 8^th to 12^th week of the pregnancy, and results in an unconstructed brain half. Yes, correct, hemispheres of the brain are not formed, and that space is filled with the fluid, which is found around the brain to protect the brain from any mechanical shock. Diagnosis of Hydranencephaly is possible from the 16^th to 26^th weeks of the pregnancy.

Because of the brain’s absence, the pressure inside the bones of the brain decreases, and skull formation gets impacted too, which leads to the formation of a small head. Patients, in the majority, die within one year of birth, and the maximum reported age with this condition is 32 years.

Many other issues arise from this, such as delay in development, seizures, muscles in the legs and hips of the patient getting stiff as neurons do not properly transmit signals, there may be a condition of numbness, and the patient might also need mechanical ventilation for a long time.⁶

Cryptorchidism

It is a medical condition in which one or both testes fail to come down in the scrotum and stay in the inguinal canal or the abdominal region. This naturally takes place on the 6th of the pregnancy; if not, then within the 3 months after the birth, descent can happen.

This is observed with fingers to locate the testes, and after 18 months of birth, surgery is recommended if the testes do not come down to sit in the scrotum.

Many complications in adulthood can occur if Cryptorchidism is kept untreated, like male infertility, semen of poor quality, the testes might not get fully developed, and the risk of testicular cancer is also increased.⁷

Shawl scrotum

Shawl scrotum is a typical condition associated with Aarskog syndrome, in which the scrotum of a newborn AMAB (a sac that holds both the testicles) is found to be covering the penis, and eventually, this resolve on its own.⁸

Inguinal hernia

In Inguinal Hernia, a cluster of intestinal tissues pops out of the wall of the abdominal region at the lower side through any weak spot in the wall. It is mostly found on each side of the groin. It is more common in AMAB as compared to AFAB. It is massaged and pushed back into the stomach; however, in many cases, it gets stuck and bulges out of the body. In these cases, the tissue set might die as it has been deprived of blood supply.⁹

Prominent umbilicus is a medical condition where the area around the navel extends outward to form a cylindrical shape.¹⁰

Joint laxity

Joint laxity is an inherited medical condition in which ligaments (tissue in the body that connects one bone with the other) are not fully developed. This makes them weak and unable to keep the bones in their positions.

There are many other complications associated with joint laxity, like pain, muscle tightness, click sounds in the joints, tiredness of extreme intensity is also felt by the patient, constipation, muscle spasms, body balancing issues, and heartbeat fluctuations are also observed too.¹¹

Abnormal auricles

Abnormal auricles are also observed, as the outer ear is not fully developed in the newborn Aarskog syndrome patient. This is often associated with middle ear problems and affects the hearing ability of the patients.

Its treatment may be surgical or prosthetic ear, and both have their issues. Surgical procedures might be dangerous as they might affect the nerves on the face, especially since the ear is not fully developed, so there are high chances that internal anatomy may be normal.

On the other hand, if a prosthetic ear is considered, it would not last for a lifelong period, and replacement would not be cost-effective.¹²

Pectus excavatum

It is a rare genetic medical condition in which the central bone of the chest seems to be retracted or sinking, and ribs are deformed. Many cases are identified after birth. It affects the patient's stamina t since the patient cannot breathe easily, as the lungs do not get enough space to expand.¹³

Ptosis

In this condition muscles of the eyes, forming the upper eyelid, are not fully developed, and the upper eyelid drooping is very much visible.⁵

Down slanted palpebral fissures

Another medical condition of the eye related to Aarskog syndrome is the downward slanting of the lower eyelid that leads to the space between the upper and the lower eyelid widening.⁶

Summary

 Aarskog syndrome occurs due to changes in the gene FGD1 and influences the growth and development of the body. It is more commonly found in AMAB as compared to AFAB. It was named after the physician, Dagfin Aarskog, who reported it for the first time in 1970.

Many types of disorders are found in patients suffering from Aarskog syndrome, such as the right and left sides of the brain are not formed and separated properly, in fact, are fused together. This does not allow a certain part of the brain (hypothalamus) to even come into existence, and all the functionalities, which the hypothalamus is supposed to perform, are never performed.

A serious health problem, like an underdeveloped brain with a fluid-filled inside, is found that leads to an underdeveloped skull, and eventually, the head gets built way smaller than normal.

Medical conditions, like ascended testes, scrotum around the penis, hernia in groins, ligaments issues that find it problematic to hold bones normally, unformed outer ear, retracted central chest bone, and underdeveloped eyes muscles are few examples of growth and developments delays associated with Aarskog syndrome.