H syndrome: Clinical, histological and genetic investigation in Tunisian patients

Abstract

H syndrome is a rare autosomal recessive disorder with characteristic dermatological findings consisting of hyperpigmentation and hypertrichosis patches mainly located on the inner thighs and multisystemic involvement including hepatosplenomegaly, hearing loss, heart abnormalities and hypogonadism. The aim of this study was to conduct a clinical and genetic investigation in five unrelated Tunisian patients with suspected H syndrome. Hence, genetic analysis of the SLC29A3 gene was performed for four patients with a clinical diagnosis of H syndrome. We identified a novel frame-shift mutation in the SLC29A3 gene in a female patient with a severe clinical presentation. Furthermore, we report two mutations previously described, the p.R363Q mutation in a male patient and the p.P324L mutation in two patients of different age and sex. This paper extends the mutation spectrum of H syndrome by reporting a novel frame-shift mutation, the p.S15Pfs*86 in exon 2 of SLC29A3 gene and emphasizes the relevance of genetic testing for its considerable implications in early diagnosis and clinical management.

H syndrome with possible new phenotypes

“…The result of brain magnetic resonance imaging was normal, and a careful ophthalmologic examination has been performed by the ophthalmologist; however, no cause has been found to explain the presence of this finding in our patient, so it may also be a novel clinical feature of H syndrome. Genital findings are reported in some patients with H syndrome; for example, scrotal masses with a swollen and retracted penis 9 . In our case, hypospadias may be a novel genital feature of this syndrome; however, it can be a coincidental finding, as its prevalence rate in Asia is 0.6 to 69 per 10,000 live births 10 .…”

H‐like syndrome successfully treated with methotrexate

“…Indeed, even in typical cases of H syndrome we can see only two or three typical clinical findings and rarely do we see all the clinical features together in one patient since there is no phenotype and genotype correlation (Molho-Pessach et al, 2008). The mutation of the SLC23A3 gene is responsible for the symptoms (Farooq et al, 2012;Jaouadi et al, 2018;Morgan et al, 2010). However, in our patient no mutation of the SLC29A3 gene was identified.…”

Pseudo-Meigs’ Syndrome in Tunisian H Syndrome Female Patient: First Case Reported

“…Our patient presented a novel frameshift mutation in exon 2, p.S15Pfs*86 reported by Jaouadi et al 11 The pathogenicity of this mutation was assessed by using in silico prediction tools showing a pathogenic influence of the mutation on the hENT3 protein function. 11 In this case, the patient demonstrated quite severe presentation with classic findings of H syndrome ( Table 1 ). Also, she is the first H syndrome patient presenting pseudo-Meigs’ syndrome.…”