Histiocytosis-lymphadenopathy Plus Syndrome

Description

The histiocytosis-lymphadenopathy plus syndrome comprises features of 4 histiocytic disorders previously thought to be distinct: Faisalabad histiocytosis (FHC), sinus histiocytosis with massive lymphadenopathy (SHML), H syndrome, and pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome (PHID). FHC described an autosomal recessive disease involving joint deformities, sensorineural hearing loss, and subsequent development of generalized lymphadenopathy and swellings in the eyelids that contain histiocytes (summary by Morgan et al., 2010). SHML, or familial Rosai-Dorfman disease, was described as a rare cause of lymph node enlargement in children, consisting of chronic massive enlargement of cervical lymph nodes frequently accompanied by fever, leukocytosis, elevated erythrocyte sedimentation rate, and polyclonal hypergammaglobulinemia. Extranodal sites were involved in approximately 25% of patients, including salivary glands, orbit, eyelid, spleen, and testes. The involvement of retropharyngeal lymphoid tissue sometimes caused snoring and sleep apnea (summary by Kismet et al., 2005). H syndrome was characterized by cutaneous hyperpigmentation and hypertrichosis, hepatosplenomegaly, heart anomalies, and hypogonadism; hearing loss was also found in about half of patients, and many had short stature. PHID was characterized by predominantly antibody-negative insulin-dependent diabetes mellitus associated with pigmented hypertrichosis and variable occurrence of other features of H syndrome, with hepatosplenomegaly occurring in about half of patients (Cliffe et al., 2009). Bolze et al. (2012) noted that mutations in the SLC29A3 gene (OMIM ) had been implicated in H syndrome, PHID, FHC, and SHML, and that some patients presented a combination of features from 2 or more of these syndromes, leading to the suggestion that these phenotypes should be grouped together as 'SLC29A3 disorder.' Bolze et al. (2012) suggested that the histologic features of the lesions seemed to be the most uniform phenotype in these patients. In addition, the immunophenotype of infiltrating cells in H syndrome patients was shown to be the same as that seen in patients with the familial form of Rosai-Dorfman disease, further supporting the relationship between these disorders (Avitan-Hersh et al., 2011; Colmenero et al., 2012).

Clinical Features

Top most frequent phenotypes and symptoms related to Histiocytosis-lymphadenopathy Plus Syndrome

  • Global developmental delay
  • Short stature
  • Generalized hypotonia
  • Pica
  • Hearing impairment
  • Hypertelorism
  • Growth delay
  • Failure to thrive
  • Sensorineural hearing impairment
  • Ptosis
And another 125 symptoms. If you need more information about this disease we can help you.
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Incidence and onset information

Not enough data available about incidence and published cases.


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Histiocytosis-lymphadenopathy Plus Syndrome Recommended genes panels

Panel Name, Specifity and genes Tested/covered
Hearing Loss Panel.

By Knight Diagnostic Laboratories - Molecular Diagnostic Center Oregon Health & Science University in United States.

ABHD12, USH1G, USH1C, ANKH, BTD, EYA1, COL2A1, PDZD7, EYA4, HSD17B4, WFS1, FOXC1, PITX2, NDP, ADGRV1, CLRN1, USH2A, PCDH15, SLC26A4, WHRN , (...)

View the complete list with 102 more genes
Specificity
1 %
Genes
100 %
SLC29A3 sequencing.

By Genetic Services Laboratory University of Chicago in United States.

SLC29A3
Specificity
100 %
Genes
100 %
SLC29A3 deletion/duplication analysis.

By Genetic Services Laboratory University of Chicago in United States.

SLC29A3
Specificity
100 %
Genes
100 %
SLC29A3.

By Institute for Human Genetics University Clinic Freiburg in Germany.

SLC29A3
Specificity
100 %
Genes
100 %
SLC29A3. Complete sequencing.

By Instituto de Medicina Genomica Instituto de Medicina Genomica in Spain.

SLC29A3
Specificity
100 %
Genes
100 %
Histiocytosis-lymphadenopathy plus syndrome (sequence analysis of SLC29A3 gene).

By CGC Genetics in Portugal.

SLC29A3
Specificity
100 %
Genes
100 %
Histiocytosis-lymphadenopathy plus syndrome.

By Centogene AG - the Rare Disease Company in Germany.

SLC29A3
Specificity
100 %
Genes
100 %
Histiocytosis Lymphadenopathy Plus syndrome - SLC29A3.

By SEALS Genetics Laboratory South Eastern Area Laboratory Services, NSW Health Pathology in Australia.

SLC29A3
Specificity
100 %
Genes
100 %
Autoinflammatory diseases Panel.

By CeGaT GmbH in Germany.

HFE, NLRP3, MVK, PSMB8, MEFV, SH3BP2, NOD2, SLC29A3, LPIN2, TNFRSF1A, IL10RA, IL10RB, PSTPIP1, NLRP12, IL36RN, CARD14, IL1RN, IL10, RBCK1, PLCG2
Specificity
5 %
Genes
100 %
Invitae Primary Immunodeficiency Panel.

By Invitae in United States.

PMS2, STAT1, SLC37A4, CASP8, TLR3, HAX1, AP3B1, UNG, TAP1, TAZ, TCN2, AK2, SLC35C1, CYBA, STAT3, ADA, MOGS, IL2RG, PNP, AIRE , (...)

View the complete list with 187 more genes
Specificity
1 %
Genes
100 %
Invitae Autoinflammatory Syndromes Panel.

By Invitae in United States.

NLRP3, MVK, PSMB8, MEFV, SH3BP2, NOD2, SLC29A3, ELANE, LPIN2, TNFRSF1A, IL10RA, NLRC4, IL10RB, ADA2, PSTPIP1, NLRP12, TRNT1, IL36RN, CARD14, IL1RN , (...)

View the complete list with 6 more genes
Specificity
4 %
Genes
100 %
Hearing Loss: Sequencing Panel.

By EGL Genetic Diagnostics Eurofins Clinical Diagnostics in United States.

ABHD12, USH1G, USH1C, BTD, EYA1, COL2A1, EYA4, HSD17B4, OPA1, WFS1, FOXC1, PITX2, ADGRV1, CLRN1, USH2A, PCDH15, SLC26A4, WHRN, CDH23, DIABLO , (...)

View the complete list with 111 more genes
Specificity
1 %
Genes
100 %
Hearing Loss: Deletion/Duplication Panel.

By EGL Genetic Diagnostics Eurofins Clinical Diagnostics in United States.

ABHD12, USH1G, USH1C, BTD, EYA1, EYA4, HSD17B4, WFS1, FOXC1, PITX2, ADGRV1, CLRN1, USH2A, PCDH15, SLC26A4, WHRN, CDH23, DIABLO, MSRB3, CISD2 , (...)

View the complete list with 71 more genes
Specificity
2 %
Genes
100 %
SLC29A3.

By Fulgent Genetics Fulgent Genetics in United States.

SLC29A3
Specificity
100 %
Genes
100 %
Comprehensive Hearing Loss and Deafness Panel.

By Blueprint Genetics in Finland.

ABHD12, USH1G, USH1C, ANKH, BTD, BCS1L, TWNK, EYA1, COL2A1, TYR, PDZD7, EYA4, HSD17B4, TRMU, WFS1, NDP, ADGRV1, CLRN1, USH2A, PCDH15 , (...)

View the complete list with 159 more genes
Specificity
1 %
Genes
100 %
Osteopetrosis and Dense Bone Dysplasia Panel.

By Blueprint Genetics in Finland.

ANKH, TYROBP, LRP5, COL1A1, SOST, TGFB1, LEMD3, TNFRSF11A, CLCN7, AMER1, CTSK, FAM20C, CA2, OSTM1, TNFSF11, TCIRG1, TNFRSF11B, PTH1R, GJA1, SLC29A3 , (...)

View the complete list with 5 more genes
Specificity
4 %
Genes
100 %
Primary Immunodeficiency Panel.

By Blueprint Genetics in Finland.

PMS2, RECQL4, STAT1, SLC37A4, CASP8, CLCN7, HAX1, AP3B1, UNG, TAP1, TCN2, AK2, SLC35C1, CYBA, STAT3, ADA, MOGS, IL2RG, PNP, AIRE , (...)

View the complete list with 255 more genes
Specificity
1 %
Genes
100 %
Autoinflammatory Syndrome Panel.

By Blueprint Genetics in Finland.

SAMHD1, RNASEH2A, RNASEH2C, RNASEH2B, TREX1, NLRP3, MVK, PSMB8, IFIH1, ADAR, MEFV, NOD2, SLC29A3, ELANE, LPIN2, TNFRSF1A, NLRC4, ISG15, PSTPIP1, NLRP12 , (...)

View the complete list with 12 more genes
Specificity
4 %
Genes
100 %
Comprehensive Skeletal Dysplasias and Disorders Panel.

By Blueprint Genetics in Finland.

RECQL4, ALPL, ANKH, TYROBP, FKBP10, B4GALT7, LRP5, COL2A1, COL1A1, COL1A2, SOST, TGFB1, LEMD3, TNFRSF11A, PYCR1, CLCN7, ATP6V0A2, FBN1, SERPINF1, SP7 , (...)

View the complete list with 226 more genes
Specificity
1 %
Genes
100 %
Comprehensive Growth Disorders / Skeletal Dysplasias and Disorders Panel.

By Blueprint Genetics in Finland.

RECQL4, ALPL, ANKH, TYROBP, FKBP10, B4GALT7, BCS1L, IFITM5, LRP5, COL2A1, COL1A1, COL1A2, COL3A1, SOST, TGFB1, LEMD3, TNFRSF11A, PYCR1, CLCN7, ATP6V0A2 , (...)

View the complete list with 288 more genes
Specificity
1 %
Genes
100 %
Histiocytosis-lymphadenopathy plus syndrome.

By Bioarray in Spain.

SLC29A3
Specificity
100 %
Genes
100 %
SLC29A3 Gene Sequencing and Deletion/Duplication Analysis.

By DDC Clinic Molecular Diagnostics Laboratory DDC Clinic, Center for Special Needs Children in United States.

SLC29A3
Specificity
100 %
Genes
100 %
Histiocytosis-Lymphadenopathy Plus Syndrome , Sequencing SLC29A3 Gene.

By Reference Laboratory Genetics in Spain.

SLC29A3
Specificity
100 %
Genes
100 %

Alternate names

Histiocytosis-lymphadenopathy Plus Syndrome Is also known as histiocytosis and lymphadenopathy with or without cutaneous, cardiac, and/or endocrine features, joint contractures, and/or deafness, hyperpigmentation, cutaneous, with hypertrichosis, hepatosplenomegaly, heart anomalies, and hypogonadism with or without hearing loss, h syndrome, pigmented hypertrichosis with insulin-dependent diabetes mellitus;phid, histiocytosis with joint contractures and sensorineural deafness;hjcd, faisalabad histiocytosis, rosai-dorfman disease, familial, sinus histiocytosis and massive lymphadenopathy;shml;.



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