Disease Profile

Histiocytosis-lymphadenopathy plus syndrome

Prevalence ?
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of Onset

Childhood

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ICD-10

D76.3

Inheritance

Autosomal dominant ?A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive ?Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked dominant ?X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked recessive ?Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic ?Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor ?Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other Names (AKA)

HJCD; Faisalabad histiocytosis; H syndrome;

Categories

Blood Diseases; Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases;

Summary

Histiocytosis-lymphadenopathy plus syndrome is a group of conditions with overlapping signs and symptoms that affect many parts of the body.[1] This group of disorders includes H syndrome, pigmented hypertrichosis with insulin-dependent diabetes mellitus (PHID), Faisalabad histiocytosis, and familial Rosai-Dorfman disease (also known as familial sinus histiocytosis with massive lymphadenopathy or FSHML). These conditions were once thought to be distinct disorders; however, because of the overlapping features and shared genetic cause, they are now considered to be part of the same disease spectrum.[1][2] While some affected individuals have signs and symptoms characteristic of one of these conditions, others have a range of features from two or more of the conditions. The pattern of signs and symptoms can vary, even within the same family.[1]

All of the conditions in the spectrum are characterized by histiocytosis, which is an overgrowth of immune system cells called histiocytes. These cells abnormally accumulate in one or more tissues in the body, which can lead to organ or tissue damage. The lymph nodes are commonly affected, leading to swelling of the lymph nodes (lymphadenopathy). Other areas of cell accumulation can include skin, kidneys, brain and spinal cord (central nervous system), or digestive tract. The spectrum is known as histiocytosis-lymphadenoapthy plus syndrome because the disorders that make up the spectrum can have additional signs and symptoms.[1]

H syndrome is named for the collection of symptoms all starting with the letter H that are commonly present. These include hyperpigmented skin lesions with excessive hair growth (hypertrichosis) and histiocyte accumulation, enlargement of the liver or liver and spleen (hepatomegaly or hepatosplenomegaly), heart abnormalities, hearing loss, reduced amounts of hormones that direct sexual development (hypogonadism), and short stature (reduced height).[1][2] In some cases, hyperglycemia/diabetes mellitus may also be present.[2]

PHID is characterized by patches of hyperpigmented skin with hypertrichosis and the development of type 1 diabetes during childhood.[1]

Faisalabad histiocytosis is characterized by lymphadenopathy and swelling of the eyelids due to the accumulation of histiocytes. Affected individuals may also have joint deformities (contractures) in their fingers or toes, and hearing loss.[1]

Familial Rosai-Dorfman disease is characterized by lymphadenopathy, most often in the neck. Histiocytes can also accumulate in other parts of the body.[1]

Histiocytosis-lymphadenopathy plus syndrome is caused by mutations in the SLC29A3 gene. The condition is inherited in an autosomal recessive pattern.[1][2] Treatment is aimed at treating the symptoms present in each individual.[1]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Decreased testicular size
Small testes
Small testis

[ more ]

0008734
Delayed puberty
Delayed pubertal development
Delayed pubertal growth
Pubertal delay

[ more ]

0000823
Histiocytosis
0100727
Hyperpigmentation of the skin
Patchy darkened skin
0000953
Scleroderma
0100324
Stiff skin
0030053
30%-79% of people have these symptoms
Camptodactyly
Permanent flexion of the finger or toe
0012385
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Hepatosplenomegaly
Enlarged liver and spleen
0001433
Hypertrichosis
0000998
Lymphadenopathy
Swollen lymph nodes
0002716
Short stature
Small stature
Decreased body height

[ more ]

0004322
5%-29% of people have these symptoms
Abnormal cardiovascular system physiology
0011025
Abnormal eyebrow morphology
Abnormality of the eyebrow
0000534
Alopecia
Hair loss
0001596
Amenorrhea
Abnormal absence of menstruation
0000141
Azoospermia
Absent sperm in semen
0000027
Bronchiectasis
Permanent enlargement of the airways of the lungs
0002110
Chronic rhinitis
0002257
Cleft upper lip
Harelip
0000204
Corneal arcus
0001084
Delayed skeletal maturation
Delayed bone maturation
Delayed skeletal development

[ more ]

0002750
Diabetes mellitus
0000819
Enlarged kidney
Large kidneys
0000105
Facial telangiectasia
0007380
Full cheeks
Apple cheeks
Big cheeks
Increased size of cheeks
Large cheeks

[ more ]

0000293
Gingival overgrowth
Gum enlargement
0000212
Gynecomastia
Enlarged male breast
0000771
Hallux valgus
Bunion
0001822
Hernia
0100790
Hydrocephalus
Too much cerebrospinal fluid in the brain
0000238
Hyperreflexia
Increased reflexes
0001347
Hypertriglyceridemia
Increased plasma triglycerides
Increased serum triglycerides
Increased triglycerides

[ more ]

0002155
Hypogonadism
Decreased activity of gonads
0000135
Ichthyosis
0008064
Intellectual disability, mild
Mental retardation, borderline-mild
Mild and nonprogressive mental retardation
Mild mental retardation

[ more ]

0001256
Lipodystrophy
Inability to make and keep healthy fat tissue
0009125
Malabsorption
Intestinal malabsorption
0002024
Microcytic anemia
0001935
Micropenis
Short penis
Small penis

[ more ]

0000054
Osteolysis
Breakdown of bone
0002797
Pes planus
Flat feet
Flat foot

[ more ]

0001763
Proptosis
Bulging eye
Eyeballs bulging out
Prominent eyes
Prominent globes
Protruding eyes

[ more ]

0000520
Psoriasiform dermatitis
0003765
Recurrent fever
Episodic fever
Increased body temperature, episodic
Intermittent fever

[ more ]

0001954
Recurrent fractures
Increased fracture rate
Increased fractures
Multiple fractures
Multiple spontaneous fractures
Varying degree of multiple fractures

[ more ]

0002757
Recurrent pharyngitis
Recurrent sore throat
0100776
Upper eyelid edema
Fullness of upper eyelid
Puffiness of upper eyelid
Swelling of upper eyelid

[ more ]

0012724
Varicose veins
0002619
1%-4% of people have these symptoms
Alopecia of scalp
Pathologic hair loss from scalp
Scalp hair loss

[ more ]

0002293
Anteverted nares
Nasal tip, upturned
Upturned nasal tip
Upturned nose
Upturned nostrils

[ more ]

0000463
Atrial septal defect
An opening in the wall separating the top two chambers of the heart
Hole in heart wall separating two upper heart chambers

[ more ]

0001631
Camptodactyly of finger
Permanent flexion of the finger
0100490
Cardiomegaly
Enlarged heart
Increased heart size

[ more ]

0001640
Cervical lymphadenopathy
Swollen lymph nodes in the neck
0025289
Clinodactyly
Permanent curving of the finger
0030084
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
0000494
Elevated erythrocyte sedimentation rate
High ESR
0003565
Episcleritis
Inflammation of the thin layer on top of the white part of eye

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Providing General Support

    Learn More

    These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

    Where to Start

    • Genetics Home Reference (GHR) contains information on Histiocytosis-lymphadenopathy plus syndrome. This website is maintained by the National Library of Medicine.

      In-Depth Information

      • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
      • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
      • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
      • PubMed is a searchable database of medical literature and lists journal articles that discuss Histiocytosis-lymphadenopathy plus syndrome. Click on the link to view a sample search on this topic.

        Selected Full-Text Journal Articles

          References

          1. Histiocytosis-lymphadenopathy plus syndrome. Genetics Home Reference (GHR). December 2014; https://ghr.nlm.nih.gov/condition/histiocytosis-lymphadenopathy-plus-syndrome.
          2. Zlotogorski A. H syndrome. Orphanet. May 2014; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=168569.