What Is Parry Romberg Syndrome?

Introduction

Parry Romberg syndrome (PRS) is a rare disorder that causes the progressive breakdown (atrophy) of facial skin and tissue and is usually seen in children and young adults.^1,2 PRS  is also known as progressive hemifacial atrophy. The cause of the syndrome is unknown, although several articles have suggested that it is an autoimmune disease or due to abnormalities during embryogenesis. The development of the disease is inconsistent, and symptoms often vary amongst individuals, making PRS very difficult to diagnose. The disease is also closely related to linear sclerosis en coup de sabre - therefore, differential diagnosis techniques are important.³

According to Boston Children’s Hospital, roughly one in 250,000 people are affected by PRS - however,  the estimate is likely inaccurate due to the high rates of misdiagnosis. Females are significantly more likely to have PRS than males, and the disease tends to be sporadic (random), with only a few cases being hereditary (genetic).⁴

This article focuses on understanding the origin of PRS, its risk factors, symptoms, diagnosis, and any possible treatments that can help individuals cope with PRS.

Historical background

The syndrome was first reported in 1825 by Caleb Parry. Moritz Romberg later detailed its neurological impacts in the 1840s, hence the name “Parry Romberg syndrome”. At the time, PRS was considered to be a manifestation of scleroderma (an autoimmune skin condition) because of the similar histology.⁵ Advancements in our knowledge of PRS have since been made, connecting the syndrome to several neurological factors and supporting the development of diagnostic tools to detect it.  Nowadays, the development of diagnostic tools such as MRIs and CT scans has allowed confirmation of a connection of PRS with neurology. Whilst our understanding of PRS continues to improve, its exact impacts on the body remain unknown, and few treatment options are available.

Causes and risk factors 

While the exact cause of Parry Romberg syndrome remains unknown, theories have been proposed to explain its development. One theory suggests that PRS is an autoimmune disease (i.e. the result of your immune system malfunctioning). Consequently, antibodies that normally fight dangerous bacteria and viruses attack your body’s healthy cells and tissues. A 2003 study supported this theory by confirming the presence of antinuclear antibodies (autoantibodies that attack healthy tissue) in PRS patients. Additionally, other autoimmune conditions like rheumatoid arthritis (RA) and inflammatory bowel disease were recorded in at least 4% of the patients.⁶

Although scientists cannot form definite conclusions yet, PRS has also been potentially associated with bacterial or viral infections like Borrelia burgdorferi.⁷Genetics may also be involved in the development of PRS, with another study finding that several proinflammatory molecules (including GFCSF3, ADAMTS4 and IL24) are all enhanced in PRS.  Nonetheless, PRS is still thought to be sporadic (randomly occurring) and has not been reported to be hereditary.⁸  Indeed, various environmental causes of PRS have been highlighted by various authors over the years, including facial trauma, overactivity of the sympathetic nervous system, nerve abnormalities, and vascular dysfunction. All in all, the causes of PRS are still inconclusive, but a combination of the possible theories stated above is likely to lead to PRS. Therefore, individuals at risk of PRS are those already presenting with the theories, like RA patients.

Signs and symptoms 

The main characteristic of PRS is the atrophy (breakdown) of facial tissue. The speed and extent of tissue degradation and loss can vary significantly between individuals.  As such, patients are categorised into different groups (ranging from mild to significant asymmetry) depending on the severity of atrophy. 

Besides this  facial atrophy, PRS can cause several neurological symptoms, including: 

• Seizures (the most common symptom)
• Headaches and migraines
• Brain atrophy
• Sympathetic hyperactivity
• Limb atrophy
• Mandibular (jaw) cramps
• Mental retardation⁴

PRS usually affects one side of the face, and individuals may experience abnormal development of hair, eyelashes, and eyebrows. Some other symptoms are dental and oral deformities. These include hemiatrophies (underdevelopment of one half) of the upper lip or tongue and abnormal jaw development or jawline. Furthermore, some patients experience vitiligo (loss of colour) in some skin areas.⁹ 

The list of possible signs and symptoms of PRS is increasingly extensive,  and some of the symptoms are seen in or are very similar to, those associated with other conditions. Symptoms also vary between individuals, potentially due to their environment and any underlying conditions they may have.

Diagnosis 

If a doctor suspects you have PRS, they will carry out a  clinical evaluation and specific tests. Healthcare professionals may use Romberg’s test as a form of clinical evaluation; if this test is positive, other neurological screening tests will likely be done. Once the doctors have confirmed your neurological symptoms, they will likely use diagnostic tools to confirm your diagnosis. The most common diagnostic tools are imaging studies like MRIs, ultrasounds, and CT scans.¹⁰ Rarely a microscopic examination of the affected skin tissue can be done to rule out linear scleroderma en coup sabre.

Due to its inconsistent presentation and shared symptoms with other disorders, differential diagnosis is 22important when diagnosing PRS. Other conditions that need to be ruled out include Rasmussen encephalitis (RE), Barraquer-Simons syndrome (BSS) and congenital hemiatrophy, as they all have similar symptoms to PRS.¹¹ RE, for example, is associated with a distinct pale background of neutrophils and chronic inflammatory cells. As such, a brain biopsy would be ideal to rule out RE.^11,12 

There are other conditions that manifest similarly to PRS, like fat necrosis, trauma, and congenital deformities.¹¹ Researchers are continually trying to develop diagnostic tools that are more accurate and specific to PRS, including potentially groundbreaking technologies such as next-generation genome sequencing. 

Treatment 

Most treatments for PRS will aim to manage your symptoms. Therefore, the treatments used will vary between patients. Methotrexate (MTX) is the standard medication administered to PRS patients. MTX slows down the body’s immune system and reduces inflammation.^11,13 Other treatments like cyclosporine are used when MX fails. Some dermatological treatments, such as skin grafts, are also involved in the management of PRS. Dental and orthodontic care are other major treatment options for the patients, as is physical rehabilitation, like the use of a chin.¹⁴ 

Surgical interventions 

  Doctors will often opt for a multidisciplinary strategy when treating PRS with surgery. The optimal timing for PRS surgery is controversial: some people believe that surgery should be delayed until PRS has manifested fully, whilst others support earlier surgeries to minimise the condition’s psychological impacts on patients.¹¹ 

Surgical strategies used in the management of PRS include:¹¹

• Alloplastic aesthetic surgery with fat injections (notably expensive)¹⁴ 
• Orthodontic surgery (cosmetic or traditional fixes)
• Skeletal and soft tissue augmentation
• Bone, skin, and fat grafts
• Eyebrow lifting and hair transplant

New treatments

A new and promising form of treatment is targeting the genes which are commonly dysregulated in PRS.  One study showed clinical improvement in  PRS patients after microvascular tissue transfer when the genes (GFCSF3, ADAMTS4 and IL24) have been dysregulated.⁸

Prognosis 

The prognosis of PRS patients varies based on the severity of their symptoms. Most people with moderate symptoms typically have cosmetic abnormalities but do not experience pain.  Further, the tissue atrophy often will not progress all the way over the face. When PRS is mild, it typically has only cosmetic consequences and doesn't create any disabilities. Overall, however, Parry-Romberg syndrome has an unclear prognosis in terms of recovery time.¹⁰

Coping strategies and support 

Many PRS patients have low self-esteem and confidence due to their facial deformities. Some patients may even develop anxiety, which can be managed with cognitive behavioural therapy or anti-anxiety medication. Support groups are an ideal way to aid both patients with PRS and their families. Additionally, it is crucial to educate the general population and promote an inclusive and respectful culture. Donations made to scientists working on PRS research and the enrollment of PRS patients into clinical trials are important as well.

Summary 

• Parry Romberg Syndrome (PRS) is a rare disorder that causes the breakdown of facial tissue and skin.
• The causes of PRS are still not certain, but previous studies suggest autoimmunity, trauma, bacteria, and genetics as possible agents.
• Neurological evaluations are used to confirm PRS diagnoses, although there are conditions that have similar manifestations; therefore, differential diagnosis is essential.
• There is no cure for the syndrome, and management usually focuses on surgical interventions for cosmetic correction.
• The prognosis varies according to the individual’s symptoms.
• Current research focuses on the use of genetics for diagnostic purposes, as well as treatment options for PRS.