What Is Proteus Syndrome?
Proteus syndrome is a rare genetic illness characterized by abnormal blood vessels, bone formation, and a variety of skin abnormalities such as café au lait macules (hyperpigmented lesions), lipomas (fatty lump), and epidermal nevi (overgrowth of epidermis). The symptoms are usually not noticeable until late infancy or early childhood. Overgrowth in different areas of the body progresses with time. Siblings or other family members are not usually affected by the illness. This disease is considered to be caused by a mosaic alteration or mutation in the AKT1 gene that occurs shortly after conception. Some cells carry the defective gene, which produces an aberrant protein that promotes cell division. Unaffected cells function normally.
What Are the Dermatological Manifestations of Proteus Syndrome?
These dermatological manifestations include,
Cerebriform Connective Tissue Nevi:
This exhibits well-defined plaques with papules and nodules of the same skin color. They are pink and have a corrugated, cerebriform look on the soles of the feet. Larger lesions had tight folds and were extremely hard. Connective tissue nevi on the soles typically appear two years after the injury. Growth starts on the balls of the feet close to the arch and spreads outward to encompass the sides and soles of the feet. Some individuals develop cerebriform connective tissue nevi on both the palms and the soles.
Connective tissue nevi occur on the forearm and abdomen, extensively across the chest, and immediately below the nasal ala. The perinasal lesions were hard, solitary, and skin-colored nodules. Cerebriform connective tissue nevi on the soles were a major cause of morbidity since they made walking difficult and painful. They may also cause foot odor, with foot ulcers and infections.
Epidermal Nevi:
It is characterized by flat-topped, tan to brown, well-defined hyperkeratotic papules in Blaschko lines. It appears as several patches distributed asymmetrically across the body. Biopsies (removal of sample tissue to identify the disease) of truncal lesions showed acanthosis and hyperkeratosis, characteristic of epidermal nevi. Vascular malformations are also observed. Pink to red blanchable macules indicated capillary malformations. Vascular malformations varied from compressible masses to localized networks of ectatic veins. Based on imaging investigations, macrocystic lymphatic malformations are seen as massive skin-colored chest wall lumps with vascular channels.
A combination of capillary-venous malformations was present in certain cases. A histological investigation showed densely aggregated, dilated capillaries and thin-walled arteries lined with a single layer of endothelial cells. The presence of capillary-microcystic lymphatic malformation with clusters of clear and hemorrhagic vesicles on a red macule. Legs and the trunk were most frequently affected by vascular abnormalities.
Lipomas:
Lipomas appeared as tumors and soft nodules with ill-defined margins. They were most frequently found on the head, groin, abdomen, and legs, ranging in size from tiny nodules to large masses infiltrating deeper tissues. Partial lipohypoplasia manifests as skin patches with limited fat and accentuated bone features. Individuals with Proteus syndrome exhibited either unilateral trunk lipohypoplasia or limb-dominant lipohypoplasia. The symptoms of dermal hypoplasia were reddish, depressed, thinner skin plaques with noticeable veins. It usually occurs on the thighs and lower legs, followed by a loss of hair and decreased subcutaneous fat.
Several patients had nonpalpable pigmentary changes. Patients had one or more slightly hyperpigmented macules. These were linear, following Blaschko's lines, or truncal macules that did not exceed the midline. Hypopigmented oval macules with strong borders and single café au lait macules may occur on the upper lip and lower back in two lesions, measuring up to 0.98 inches in their largest dimension.
Other Findings:
Individuals present with isolated patches or relative hypertrichosis of one extremity. Hair development was reduced in specific areas, including thin and sparse scalp hair, sparse brows, and lateral brow loss. Low hairline in front, low hairline in back, and lighter-colored regions on the scalp. Patients experienced nail anomalies, which were often limited to a few nails. Nail abnormalities included brachyonychia, koilonychia, thick and thin nails, and bluish nails.
Most patients had asymmetric craniofacial structures, including face asymmetry, a low nasal bridge, widened or anteverted nares, down-slanting palpebral fissures, and asymmetric ears. Oral observations included heterochromia iridis, gingival overgrowth, crowded teeth, a high-arched palate, and noticeable tongue papillae.
What Are the Extracutaneous Symptoms of Proteus Syndrome?
The categories for extracutaneous symptoms included deformity, tumors, cysts, vascular anomalies, visceral overgrowth, skeletal overgrowth, other overgrowth, hypoplasia or maldevelopment, and cysts. Each patient had some degree of overgrowth in their hands or feet, particularly in the fingers and toes. The second most prevalent type of skeletal overgrowth was overgrowth of the arms or legs. It affects about 23 % of patients, primarily affecting the knees and limiting joint motion.
Hyperostotic overgrowth of the external auditory canal and skull was 58 % and 25 %, respectively. Spleen enlargement occurs in 33 % of the patients, and kidney enlargement occurs in 17 %. 46 % of patients had fat infiltration (affecting the heart, pancreas, spinal cord, or, paraspinous region, or other organs, while 38 % of patients had pharyngeal or vocal cord enlargement.
The most common types of tumors were peribulbar dermoid of the eye, detected in 29 % of the patients, and ovarian cystadenoma, a benign ovarian tumor, found in 33 % of patients. Cysts were detected in the lungs in 21 % of the patients and in the brain in 17 % of the patients. Scoliosis and chest asymmetry were present in 71 % and 54 % of the patients. Hernias, hydrocele, and undescended or missing testes were seen in 29 % of the fourteen male patients, with some having more than one of these abnormalities. Tracheomalacia and muscular hypoplasia affected 13 % of the individuals.
Conclusion
Proteus syndrome patients exhibit a range of extracutaneous and cutaneous abnormalities, such as tumors, malformations, deficient growth, and overgrowth. Dermatologists can help diagnose and treat the numerous skin abnormalities associated with Proteus syndrome. Coordinating care among various specialists, such as orthopedic surgeons, general surgeons, oral and maxillofacial surgeons, ophthalmologists, dermatologists, otolaryngologists, urologists, gynecologists, geneticists, genetic counselors, and radiologists, can be done by a pediatrician or internist. Patients with Proteus syndrome require a multidisciplinary approach due to the diverse range of abnormalities.
