|Year : 2015 | Volume
| Issue : 2 | Page : 102-104
The H syndrome
Sharad Mehta, Vaishali Masatkar, Asit Mittal, Ashok K Khare, Lalit K Gupta
Department of Dermatology, Venereology and Leprosy, RNT Medical College, Udaipur, Rajasthan, India
|Date of Web Publication||9-Apr-2015|
8A, Tulsinagar, Near Sai Baba Temple, Hiranmagri, Sector 5, Udaipur, Rajasthan
Source of Support: None, Conflict of Interest: None
The H syndrome is a rare autosomal recessive genodermatosis caused by mutations in the nucleoside transporter hENT3. It is characterized by progressive skin sclerosis, hyperpigmentation, and hypertrichosis, along with multiple systemic manifestations including insulin-dependent diabetes mellitus. We report this case for its rarity.
Keywords: Genodermatosis, H syndrome, rare case
|How to cite this article:|
Mehta S, Masatkar V, Mittal A, Khare AK, Gupta LK. The H syndrome. Indian J Paediatr Dermatol 2015;16:102-4
| Introduction|| |
Hsyndrome is an autosomal recessive genodermatosis having various consellation of features like: Hyperpigmentation, hypertrichosis, hepatosplenomegaly, hearing loss, heart anomalies, hypogonadism, low height (short stature), hyperglycemia/diabetes mellitus, and hallux valgus/flexion contractures etc.  It is now considered as a novel inherited form of histiocytosis. 
| Case report|| |
A 13-year-old boy presented with 1-year history of asymptomatic progressive cutaneous sclerosis, hyperpigmentation and hypertrichosis over both thighs and trunk. He was diagnosed as Type 1 diabetic 8 months back and was receiving insulin therapy since then. He had a history of recurrent fractures with trivial trauma since childhood. History of consanguinity and family history of similar illness was negative.
His cutaneous examination revealed multiple ill-defined hyperpigmented indurated plaques over the medial aspect of both thighs and anterior trunk [Figure 1]a]. Lesions over thighs were associated with hypertrichosis and were warm to touch. General physical examination was normal except mild hepatomegaly. Skeletal examination revealed flat foot, hallus valgus and flexion contractures of fingers [Figure 1]b]. Psychiatric evaluation showed borderline intelligence (SQ/IQ = 72) according to Vineland social maturity scale interpretation. Ophthalmologic (except for exophthalmos), auditory, and neurological evaluations were normal.
|Figure 1: (a) Hyperpigmented, hypertrichotic, indurated plaque over medial aspect of thighs bilaterally. (b) Flexion contractures of fingers and hallus valgus|
Click here to view
Routine laboratory investigations revealed a fasting blood glucose level of 350 mg/dL with HbA1c 13.8% and urine glucose 3 + . Thyroid profile, serum testosterone, follicle stimulating hormone and luteinizing hormone levels were normal. Antinuclear antibodies titer was negative. Skin biopsy as shown in [Figure 2]a showed sclerotic dermis with several interstitial scattered fibrocytes and thickened collagen bundles replacing part of subcutaneous tissue. A perivascular infiltrate of histiocytes with foamy cytoplasm was seen. Immunohistochemistry studies showed CD68 and CD45 positivity in dermal perivascular histiocytic infiltrate [Figure 2]b] and CD34 + in vessel endothelium. Skeletal radiographs revealed flexion deformities of hands and hallus valgus. Bone density scan showed osteoporotic changes.
|Figure 2: (a) Histopathology showing thickened collagen bundles and a perivascular infiltrate of histiocytes (H and E, ×40). (b) Immunohistochemical study showing CD68+ perivascular histiocytic infiltrate in dermis|
Click here to view
Ultrasound abdomen revealed mild hepatomegaly. Color Doppler study of scrotum showed bilateral funiculitis, small left testis and right side mild hydrocele. Venous Doppler study of both thighs showed increased vascularity from femoral blood vessels, increased thickening and echogenicity of skin and subcutaneous tissue. Echocardiography revealed mild tricuspid regurgitation. Chest radiography and nerve conduction studies were normal.
| Discussion|| |
H syndrome is a multisystemic disease with clinical variability, the hallmark being characteristic cutaneous hyperpigmentation accompanied by sclerodermatous thickening and hypertrichosis.  Systemic manifestations include hepatosplenomegaly, hearing loss, heart anomalies, hypogonadism, low height, hyperglycemia, and hallux valgus/flexion contractures, etc., It is caused by mutations in SLC29A3 gene that encodes for the human equilibrative nucleoside transporter 3.  It is now considered as a novel inherited form of histiocytosis. 
Initially, on the basis of cutaneous findings, we thought of pseudoscleroderma as a possibility, later on the constellation of symptoms and signs pointed towards H syndrome.
Possibility of polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome  was excluded as there were no neurological deficits. Also, edema of the legs and angiomas is characteristic of POEMS syndrome, which was not seen in our patient.
Another close mimic pigmented hypertrichosis with insulin-dependent diabetes mellitus  was ruled out due to absence of dysmorphic features, lack of lab evidence of chronic inflammation (normal erythrocyte sedimentation rate and C-reactive protein) and lack of plasma cell infiltrate in cutaneous histopathology.
Rosai-Dorfmann syndrome has clinical, histopathological and immunophenotypical overlap with H syndrome,  but it is characterized by massive, painless lymphadenopathy and emperipolesis. In a recent study, lymphadenopathy was present in 24% patients of H syndrome and it has been suggested that a common pathogenetic mechanism exists for both these disorders.  However, lymphadenopathy was not seen in our patient.
Histopathologically, cutaneous lesions of H syndrome show dermal and subcutaneous fibrosis with lymphohistiocytic infiltrate expressing CD68, CD34 and factor XIIIa.  CD34 positivity in vessel endothelium, and CD45 and CD68 positive dermal histiocytes were observed in our patient.
Almost 100 cases of H syndrome have been reported; majority from Arab region.  Recently, four new cases have been reported from India.  It is possible that cases go undiagnosed or are not diagnosed properly because of its overlapping features with other syndromes. As cutaneous manifestations are the hallmark of the syndrome, dermatologists play an indispensable role in the identification of these patients.
| References|| |
Molho-Pessach V, Agha Z, Aamar S, Glaser B, Doviner V, Hiller N, et al.
The H syndrome: A genodermatosis characterized by indurated, hyperpigmented, and hypertrichotic skin with systemic manifestations. J Am Acad Dermatol 2008;59:79-85.
Molho-Pessach V, Lerer I, Abeliovich D, Agha Z, Abu Libdeh A, Broshtilova V, et al
. The H syndrome is caused by mutations in the nucleoside transporter hENT3. Am J Hum Genet 2008;83:529-34.
Molho-Pessach V, Ramot Y, Camille F, Doviner V, Babay S, Luis SJ, et al.
H syndrome: The first 79 patients. J Am Acad Dermatol 2014;70:80-8.
Marina S, Broshtilova V. POEMS in childhood. Pediatr Dermatol 2006;23:145-8.
Prendiville J, Rogers M, Kan A, de Castro F, Wong M, Junker A, et al.
Pigmented hypertrichotic dermatosis and insulin dependent diabetes: Manifestations of a unique genetic disorder? Pediatr Dermatol 2007;24:101-7.
Avitan-Hersh E, Mandel H, Indelman M, Bar-Joseph G, Zlotogorski A, Bergman R. A case of H syndrome showing immunophenotye similarities to Rosai-Dorfman disease. Am J Dermatopathol 2011;33:47-51.
Doviner V, Maly A, Ne'eman Z, Qawasmi R, Aamar S, Sultan M, et al.
H syndrome: Recently defined genodermatosis with distinct histologic features. A morphological, histochemical, immunohistochemical, and ultrastructural study of 10 cases. Am J Dermatopathol 2010;32:118-28.
Molho-Pessach V, Varma M, Godbole K, Kamath N, Zlotogorski A. H syndrome - four new patients from India. Indian J Dermatol Venereol Leprol 2014;80:579.
[Figure 1], [Figure 2]