Bilateral Symmetrical Hyperpigmented Patches on the Lower Extremities

Case History A 12-year-old Iranian boy was admitted for the treatment of his skin lesions of the lower extremities since his infancy period. The skin lesions developed from both ankles as pigmented patches at 9 months. Then, pigmented skin lesions gradually increased in size and covered both legs and the inner side of both thighs. The patient's results from a consanguineous marriage, and two siblings, a boy and a daughter, were normal. The parents were normal and did not have a similar disease in their family. Physical examination showed the patient had a prominent forehead, hypertelorism, long eyelashes, large and prominent eyes, short stature, a height of 123 cm (123 vs. 149) and 27 kg weight. There was a 3 × 2 cm mass on the right side of the bridge of his nose. This finding appeared at age 10 and progressively increased in size. The nose, ears and oral cavity examination was within the normal limit. The eye examination revealed exophthalmia and telecanthus. Both corneas were clear, and the retina was normal. Both eyes were myopia and astigmatism. Physical examination of the rest of the body, including mucous membranes, and the skeletal system was normal. Dermatologic findings included bilateral symmetrical well-defined, indurated hyperpigmented patches on the inner side of both thighs and involvement of shins and calves of the legs. The leg lesions showed significant hypertrichosis. Both popliteal regions were normal without skin lesions [Figures 1-3].Figure 1: Symmetrical hyperpigmented, marked hypertrichosis and indurated plaques over the medical aspects of the thighs and legFigure 2: Markeked hyperpigmented, hypertrichotic indurated plaques on the legsFigure 3: Mild hallux valgus deformity of the great toesRoutine laboratory investigations showed complete blood cell count, liver function tests, fast blood sugar, HbA1c, creatinine, blood urea nitrogen, serum calcium and phosphorus were normal. The result of vitamin D (25-OH vitamin) was 20 ng/ml and insufficient. Chest X-ray revealed the cardiac, thoracic ratio is increased. The patient was referred to a pediatric cardiologist for more evaluation. The echocardiography findings included mild mitral valve prolapse and trivial mitral regurgitation. Abdominopelvic ultrasonography was performed. This investigation was typical except for the presence of two bilobed oval hypoechoic lymph nodes at the right side of the abdominal cavity at the level of the umbilicus. A sonogram of the scrotum in the recumbent and standing with Valsalva's manoeuvre was performed, assessing the grayscale 12 MHz appearance. The final impression was a normal study. For screening paranasal sinuses (PNS) with computerized tomography (CT), spiral PNS CT scanning was done, revealing the ground-glass appearance and maxillary and sphenoid bones hyper-density. These findings were suggestive of bilateral fibrous dysplasia and maxillary sinuses development. A skin biopsy was taken from a pigmented lesion of the thigh. The histopathology study revealed mild irregular acanthosis and basal layer hyperpigmentation of the epidermis. The dermis showed significant thickening of collagen bundles in the upper and mid-dermis with mild perivascular infiltration of lymphocytes [Figures 4 and 5].Figure 4: The epidermis shows mild irregular acanthosis and multiple sections of arrector pili muscles (Hematoxylin-eosin × 40)Figure 5: The dermis showed significant thickening of collagen bundles in the upper dermis with a mild perivascular infiltrate of lymphocytes (Hematoxylin-eosin ×100)To evaluate the mass on the right side of the bridge of the nose of the patient, he referred to an ENT man. The patient's parents refused the suggestion of a histological examination of the mass because of general anaesthesia and the consequences of surgery. What is your diagnosis? Answer: H syndrome Discussion H syndrome is a novel histiocytic genetic disorder caused by a mutation in the SLC29A3gene, which encodes protein h ENT3 with a significant role in the functions of the mitochondrial membranes, endosomes and lysosomes.[1,2] The most clinical findings in the H syndrome include hyperpigmentation, hypertrichosis, hepatosplenomegaly, heart anomalies, hearing loss, hypogonadism, hyperglycemia (insulin-dependent diabetes mellitus), short stature and skeletal abnormalities (hallux valgus, flexion contractures).[1,2] H syndrome is a relatively new entity, and cases are increasing. According to reporting cases, most H syndrome patients have been visited by different specialities before the final diagnosis. Since the skin findings including indurated hyperpigmented skin lesions accompanied by hypertrichosis involving the medial thighs and shins with sparing the knees have been seen in 68% of patients, these findings are pathognomic.[3] In the literature, approximately 100 cases of H syndrome have been reported.[2] We diagnosed the patient clinically as hyperpigmented, with hypertrichosis and indurated skin lesions of the lower extremities, pathognomonic for the H syndrome. The histopathological study of skin lesions supported the condition. Histopathology of cutaneous lesions of H syndrome shows widespread dermal and subcutaneous fibrosis with cells similar to histiocytes with irregular nuclei and nodular aggregation of lymphocytes and scattered plasma cells.[1] Although less than 15% of H syndrome patients show additional systemic features,[4] a systematic review is necessary. Our case did not have hearing loss and diabetes mellitus, and only 20% of cases showed diabetes mellitus.[5] These findings may occur younger before cutaneous conditions.[1] Our patient showed only mild cardiomegaly, mitral valve prolapses and trivial mitral regurgitation. Although previous studies have reported a wide range of cardiac anomalies in H syndrome, including atrial septal defect, ventricular septal defect, mitral valve prolapse, cardiomegaly, pulmonary hypertension, left ventricular dilation, acute coronary syndrome, pericarditis, left superior vena cava, pericardial effusion and pulmonary stenosis, but pericardial conditions are the most prevalent cardiovascular anomalies in patients with H syndrome.[1] In some cases of H syndrome, genital abnormalities such as hypospadias, and scrotal masses with swollen and retracted penis have been reported.[5] Learning points H syndrome is a novel histiocytic genetic disorder caused by a mutation in the SLC29A3gene. The pathognomonic sign of H syndrome is indurated hyperpigmented skin lesions accompanied by hypertrichosis involving the medial thighs and shins while sparing the knees. Less than 15% of H syndrome patients show additional systemic features, so a systematic review is necessary. In H syndrome, 20% of cases show diabetes mellitus. A wide range of cardiac anomalies have been reported in H syndrome, but the most prevalent cardiovascular anomalies are pericardial conditions. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.