Proteus syndrome in a young adolescent

1Medical Student, University College Dublin, Dublin, Ireland
2Resident Physician, Department of Psychiatry, University of Chicago, Chicago, IL
3Emeritus Professor, McGovern Medical School, Houston, TX

Matthews M, Rosas L, Mazur L. Proteus syndrome in a young adolescent. Consultant.
Published online May 23, 2022. doi:10.25270/con.2022.03.00004

Received October 22, 2021; accepted on November 8, 2021.

The authors report no relevant financial relationships. The authors report that informed consent was
obtained for the publication of the images used here.

Miriam Matthews, University College Dublin, Belfield, Dublin 4, Ireland ([email protected])

Proteus syndrome (PS) is a rare, progressive and asymmetric overgrowth syndrome that manifests with symptoms of varying severity. This case report presents a 13-year-old boy with progressive left leg enlargement that was initially mistaken for filariasis. PS most commonly affects the limbs and occasionally presents with hamartomas and vascular malformations. Due to the progressive nature and risk of complications, such as limb length discrepancy, deep vein thrombosis, skin ulcerations and malignant neoplasms, PS should be considered in a differential diagnosis with other overgrowth syndromes .

Keywords: Proteus syndrome, overgrowth syndrome, hamartomas, vascular malformation

During a medical mission in Tumbes, Peru, a 13-year-old boy presented with an enlarged left leg. The father said his son’s leg had been growing steadily since infancy. He said many treatments for parasitic diseases had not helped. Family history was negative for anyone with similar results.

The boy’s physical examination was notable for a body mass index over 95% for his age, an enlargement of his left leg with areas of cratered scarring below the knee and a discrepancy in leg length. (Figures 1 and 2).

Figure 2

No other part of the body was affected. He had no macrocephaly, ocular abnormalities, hemangiomas, nevi or scoliosis.

Differential diagnoses included hemihyperplasia, Proteus syndrome (PS) and Klippel-Trenaunay syndrome (KTS) (Table). Due to the gradual widening of the leg and the absence of vascular markings, PS was considered the most likely diagnosis.1


A rare genetic disorder, PS manifests as a progressive and asymmetrical proliferation of the limbs with occasional hamartomas and vascular malformations.1.2 Its prevalence is estimated between 1:1,000,000 and 1:10,000,000.1 He was named by Hans-Rudolf Wiedemann in 1983 after the shape-shifting Greek god Proteus, and Joseph Merrick (the so-called “Elephant Man”) is believed to have had PS.3 Patients with PS usually have no abnormalities at birth but develop asymmetric and irregular proliferation between 6 and 18 months.1 Proliferation continues until adolescence, then levels off.1.4 The limbs are most often affected but the location and severity of the deformities may vary.5

PS is thought to be caused by somatic mosaicism in the AKT1 gene on chromosome 14.1.2 It belongs to a class of genes known as oncogenes and provides instructions for making AKT1 kinase. The protein is found in various cells in the body and plays a vital role in signaling pathways. Non-mosaic mutations are thought to be lethal, but a duplication of the AKT1 gene responsible for PS has been reported.1.6 As MS is not genetically inherited, offspring are not at increased risk and prenatal testing is not required.1 However, few patients with PS have reproduced.1 Diagnosis is usually based on clinical findings, but can be confirmed by blood tests. AKT1 mutations.1 However, because mosaicism can be limited to certain tissues, testing is difficult.6 Unfortunately, imaging and testing for our patient was not possible due to remoteness.

Complications vary in severity and may include dermatological malformations, central nervous system manifestations, pulmonary embolisms, skeletal proliferation, and deep vein thrombosis (DVT).1 Although patients may have cutaneous capillary malformations, venous and arterial malformations are less common.5

A pathognomonic sign is the presence of cerebriform connective tissue nevi (CCTN) which most often appear on the palms and soles of the feet.2.5 The lesions were not observed at birth but develop slowly during adolescence.5 This pattern of brain grooves thickens over time and complicates hygiene in the affected areas.2.5 Their presence also distinguishes PS from KTS.4 Linear epidermal nevi are also a common manifestation and darken over time.1.5

Central nervous system manifestations occur in 40% of patients, mental retardation in 30% and epilepsy in 10%.
Hydrocephalus, hemimegalencephaly, Dandy-Walker malformations, polymicrogyria, heterotopia and various cysts have also been reported.4 Benign and malignant neoplasms such as ovarian cystadenomas, parotid adenomas, mesotheliomas, and proliferation of the spleen, liver, and lungs may also occur.1.2 Facial phenotypes may include dolichocephaly, downward sloping palpebral fissures, low nasal bridge, enlarged nostrils, long face, and open mouth at rest.4.5 Craniofacial abnormalities such as hyperostosis and unilateral condylar hyperplasia also occur.4 The bony growths can calcify and further deform and restrict movement at the affected joints.1.5 Leg length discrepancies of 20cm, scoliotic curves over 90 degrees and delayed bone age are also possible.1,5,7 Dysregulation of adipose tissue can lead to both lipoatrophy and proliferation.2 Lipoatrophy usually occurs in the chest while fatty proliferation occurs in the abdomen and extremities.5

Treatment options address complications as they arise. Guidelines recommend skeletal study, chest CT scans, and abdominal magnetic resonance imaging to identify lung lesions and abdominal lipomas.4 Several orthopedic procedures may be required for skeletal proliferation. Reduction osteotomies (selective removal of bone tissue to reduce overgrowth) and epiphysiodesis (removal of the epiphyses to arrest growth) may be beneficial. Shoe lifts and custom-made shoes can help with minor leg length discrepancies. Spinal fusion for spinal proliferation and surgical correction of
scoliosis can stop kyphoscoliosis and prevent lung damage.1.4

If CCTN develops, a dermatologist can help manage hygiene and pressure ulcers.1 Pedorthic (podiatric services) and surgical intervention to remove the plantar CCTN may be required. 1 Surgical treatment of fatty proliferation can be difficult due to diffuse proliferation.1

Patients of all ages are at high risk for pulmonary embolism and DVT, especially during surgical procedures. Therefore, perioperative anticoagulant prophylaxis is recommended.5 Procoagulants or drugs that promote growth (such as steroids) should be avoided due to the risk of DVT.

When possible, consultations in genetics, pediatrics, dermatology and orthopedics are useful. Patients and caregivers may feel isolated due to the progressive disfigurement, so all may benefit from a referral to behavioral health care providers and family support groups.4 Life expectancy for PS depends on the severity of the complications but varies between 9 months and 29 years.2 The father was informed of the possible complications and given a guarded prognosis and life expectancy for a patient with MS.

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