| Version 01 | April 2017

Procedural document:
Rare disease nomenclature in English

www.orpha.net www.orphadata.org
Table of contents

I. Introduction ................................................................................................................................................... 4
1. Purpose/objectives ................................................................................................................................... 4
2. Disclaimer ................................................................................................................................................ 4
3. Range of application ................................................................................................................................ 4
4. References ............................................................................................................................................... 4
5. Definitions ............................................................................................................................................... 5
6. Filing and updates .................................................................................................................................... 5
II. METHODOLOGY ...................................................................................................................................... 6
1. Flowchart ................................................................................................................................................. 6
2. Description............................................................................................................................................... 6
III. Naming Rules ............................................................................................................................................. 8
1. Formal rules ............................................................................................................................................. 8
a) Grammatical number ........................................................................................................................ 8
b) Diacritics and special letters ............................................................................................................. 8
c) Greek letters ..................................................................................................................................... 8
d) Capital letters.................................................................................................................................... 8
e) English orthographic variants........................................................................................................... 9
f) Hypens ................................................................................................................................................. 9
g) Chemical nomenclature .................................................................................................................. 10
h) Gene nomenclature ......................................................................................................................... 10
i) Protein nomenclature ......................................................................................................................... 10
2. General editorial rules ........................................................................................................................... 10
a) Priority to clinical practice ............................................................................................................. 10
b) Word order ..................................................................................................................................... 11
c) Latin expressions ............................................................................................................................ 11
d) Former nomenclatures .................................................................................................................... 11
e) Comparative use of certain words .................................................................................................. 11
f) Common ways of naming diseases .................................................................................................... 13
g) Providing contrast between similar diseases .................................................................................. 15
h) Acronyms as preferred terms ......................................................................................................... 17
3. Specific editorial rules ........................................................................................................................... 17
a) Deletions and duplications of chromosomes .................................................................................. 17
b) Metabolic diseases.......................................................................................................................... 18

Procedural document on Rare disease nomenclature in English. April 2017 – Number 01 2

www.orpha.net/orphacom/cahiers/docs/GB/Disease_naming_rules_in_English_R1_Nom_01.pdf
 c) Endocrinology ................................................................................................................................ 18
d) Infectiology-parasitology ............................................................................................................... 19

Procedural document on Rare disease nomenclature in English. April 2017 – Number 01 3

www.orpha.net/orphacom/cahiers/docs/GB/Disease_naming_rules_in_English_R1_Nom_01.pdf
I. Introduction
1. Purpose/objectives
There is no international consensus so far, on how rare diseases should generally be named. This document
aims to define a set of rules to be used in the Orphanet database in order to promote a correct nomenclature.
As far as possible the Orphanet nomenclature is:
 Based on clinical practice ;
 Validated by experts of the field;
 Comprehensive;
 Consistent ;
 Stable, as far as possible when taking into account the rate of evolution of scientific knowledge.
A good name must be self-sufficient and should avoid ambiguity with similar diseases.

2. Disclaimer
 This publication is part of Joint Action 677024 RD-ACTION which has received funding from the
European Union’s Health Programme (2014-2020).

 The content of this publication represents the views of the author only and is his sole responsibility; it can
not be considered to reflect the views of the European Commission and/or the Consumers, Health,
Agriculture and Food Executive Agency or any other body of the European Union. The European
Commission and the Agency do not accept any responsibility for use that may be made of the information
it contains.

3. Range of application
The present naming rules apply to all disorder entities listed in the Orphanet database, whatever their typology
(groups of disorders, disorders or subtypes).
The Orphanet nomenclature of rare diseases is managed by the information scientists in charge of disease
inventory and classification, under responsibility of the scientific director. Experts are regularly consulted to
adjust decisions.

4. References
Some international biomedical terminologies are consulted to implement the rules defined here:
 International Classification of Diseases, version 10 (ICD-10, edited by the World Health Organization).
 International Classification of Diseases for oncology, version 3 (ICD-O-3, edited by the World Health
Organization).
 MeSH (Medical Subject Headings) (http://www.ncbi.nlm.nih.gov/mesh).
 International Union of Pure and Applied Chemistry - IUPAC.
 International Union of Biochemistry and Molecular Biology - IUBMB.
 HUGO Gene Nomenclature Committee - HGNC.
 UniProt knowledgebase – UniProt-KB.
 Fima Lifshitz (ed.), Pediatric Endocrinology, New York: Informa Healthcare, cop. 2007, vol. 2, ISBN

Procedural document on Rare disease nomenclature in English. April 2017 – Number 01 4

www.orpha.net/orphacom/cahiers/docs/GB/Disease_naming_rules_in_English_R1_Nom_01.pdf
 978-1-420-04270-2. Ch. 1 “Worrisome Growth”, p.1
Orphanet procedures:
 Orphanet inventory of rare diseases
 Procedures on experts’ selection procedures is going to be published soon.

5. Definitions
Acronyms are included only when actually used in literature: convenience acronyms used in Orphanet
summaries that have no use in the scientific community are not included. Several entities can share the same
acronym.

Editorial rules are a set of good practices aimed at ensuring some degree of consistency in the nomenclature.
They deal with the semantic content of the nomenclature. In contrast with formal rules, they should be regarded
as recommendations rather than prescriptions, and are interpreted by the information scientists according to
the context of the relevant disease.

Experts mentioned in this procedural document are the health professionals identified by Orphanet as leaders
in the medical field for a rare disorder or a group of rare disorders.

Formal rules are designed to ensure consistency of spelling and grammar throughout the Orphanet
nomenclature. They do not deal with the semantic content of nomenclature. They form a conventional
reference frame; their prescriptions are not supposed to be interpreted, but to be applied whatever the context.

Keywords are significant terms for a disease or group of disease, that are usefully retained for redirecting users
to relevant diseases, but do not fit the defining criteria of a preferred name, a synonym or an acronym.
Keywords are displayed only in the intermediary disease list produced by a request.

The ORPHA code is the unique identifier attributed by the database to each entry.

Preferred terms are usually the most generally accepted name in the medical community. This can be defined
by:
 A published consensus;
 The opinion of experts of the relevant medical specialty;
 Compelling predominance of the name in medical literature.
Preferred terms are unique throughout the database, associated to one ORPHA code only.

Synonyms are perfect equivalents in scope of the preferred term they are attached to. As many synonyms as
necessary are added to a preferred term. Sub entities are not included among synonyms.

6. Filing and updates

This document is updated at least annually or more frequently if necessary by the information scientist in
charge of disease inventory and classification. The most up-to-date version is available on the Orphanet
website: www.orpha.net/orphacom/cahiers/docs/GB/Disease_naming_rules_in_English_R1_Nom_01.pdf

Procedural document on Rare disease nomenclature in English. April 2017 – Number 01 5

www.orpha.net/orphacom/cahiers/docs/GB/Disease_naming_rules_in_English_R1_Nom_01.pdf
II. METHODOLOGY
1. Flowchart

2. Description
Data coming from scientific sources are analysed by the information scientist in charge of the rare diseases
inventory.
According to the naming rules described below, the information scientist implements modifications of the
nomenclature of rare diseases into the Orphanet database. If these modifications are only a result of formal
rules, they do not go through scientific validation.
Otherwise, the manager of the rare disease database (i.e. when a semantic rule is applied for internal
consistency), or an expert (i.e. when a decision should be done regarding the preferred term versus a synonym),

Procedural document on Rare disease nomenclature in English. April 2017 – Number 01 6

www.orpha.net/orphacom/cahiers/docs/GB/Disease_naming_rules_in_English_R1_Nom_01.pdf
or both, validate the new nomenclature.
Quality control is set up by the information scientist who regularly assesses the implementation of the formal
and editorial rules.
Orphanet rare disease nomenclature is released at a variable frequency depending on the channel of
dissemination (daily for the website - www.orpha.net -, monthly for the Orphanet download platform -
www.orphadata.org - and the Orphanet Rare Disease Ontology – ORDO, and bi-annually for the Orphanet
Report Series “List of rare diseases”).

Procedural document on Rare disease nomenclature in English. April 2017 – Number 01 7

www.orpha.net/orphacom/cahiers/docs/GB/Disease_naming_rules_in_English_R1_Nom_01.pdf
III. Naming Rules
1. Formal rules
a) Grammatical number
The general rule is to create every name in the singular, even for groups of diseases.
E.g. ORPHA93665 Autoinflammatory syndrome

Exceptions is made if using the singular would result in an inaccuracy or if using the singular is grammatically
impossible.
E.g. ORPHA1200 Choanal atresia-deafness-cardiac defects-dysmorphism syndrome

In case of multiple involvement, grammatically plural names are used.

E.g. ORPHA2505 Multiple benign circumferential skin creases on limbs

Attributive nouns, i.e. nouns used like adjectives, have a tendency to remain invariably singular, even if a
plural may appear semantically more appropriate:
E.g. ORPHA182095 Interstitial lung disease

b) Diacritics and special letters

They occur quite often in eponyms. The general rule is to keep diacritics of the original language.
E.g. ORPHA117 Behçet disease (cedilla - Turkish)
ORPHA1532 López-Hernández syndrome (acute accent - Spanish)
ORPHA99873 Hand-Schüller-Christian disease (umlaut - German)
ORPHA178333 Åland Islands eye disease (ring - Swedish)

However, the implementation of this rule is currently limited by the lack of system support for some additional
letters.

c) Greek letters
Greek letters are mentioned by their name spelt in the Roman alphabet, not by their shape in the Greek alphabet.
E.g. ORPHA60 Alpha-1-antitrypsin deficiency
ORPHA100024 Mu heavy-chain disease

d) Capital letters
The first letter of every disease name is a capital. The first letter of every proper name is a capital.
When both an acronym and its developed forms are given as possible names of an entity, the letters of the
developed form are not capitalised.
E.g. ORPHA2576 MULIBREY nanism has as a synonym the developed form Muscle-liver-brain-eye
nanism, not MUscle-LIver-BRain-EYe nanism.

When a disease name is made up of a list of signs, the individual signs are not capitalised.
E.g. ORPHA964 Acromegaly-cutis verticis gyrata-corneal leukoma syndrome

Procedural document on Rare disease nomenclature in English. April 2017 – Number 01 8

www.orpha.net/orphacom/cahiers/docs/GB/Disease_naming_rules_in_English_R1_Nom_01.pdf
 e) English orthographic variants
The general rule is to use American rather than British spellings in the nomenclature. The rationale for this
choice is to make copying-and-pasting from and to Pubmed easier, since American spellings predominate in
scientific literature.

f) Hypens

i. Compound modifiers
Compound modifiers are made of two or more attributive words used together like an adjective to modify a
noun or noun phrase. Their elements are joined by a hyphen.
E.g. ORPHA297 Tick-borne encephalitis
ORPHA208650 Cryopyrin-associated periodic syndrome

ii. Prefixes
Some prefixes (co-, pre-, post-, mid-, de-, non-, anti-, auto- etc.) may be fused or hyphenated. Many long-
established words, such as antibody do not require a hyphen since the prefix is fully fused.
Orphanet’s editorial choices are the following:
 Hyphen after non;
 Hyphen before proper nouns and abbreviations;
 Hyphen when the prefix applies to an expression rather than a single word;
 Fusion in all other cases.
Examples with non:
ORPHA2698 Non-rhizomelic chondrodysplasia punctata

Examples with proper nouns and abbreviations:

ORPHA1229 Pseudo-TORCH syndrome
ORPHA2981 Pseudo-Zellweger syndrome

Examples with expressions:

ORPHA375 Anti-glomerular basement membrane disease

Examples with fusion:

ORPHA758 Pseudoxanthoma elasticum

Fusion is used even when it puts vowels in hiatus:

ORPHA98375 Autoimmune hemolytic anemia

iii. Words made of Greek and Latin stems

A large part of the scientific vocabulary is built from Greek and Latin stems that cannot occur by themselves
in English, but are freely associated to create new names. Examples: cardio-, cephalo-, cerebro-, dermato-,
entero-, naso-, oro- etc. as first elements, -cyte, -emia, -pathy, -penia, -uria etc. as last elements.
Hyphenation rules for words made of such stems are variable. Orphanet’s editorial choice is to fuse the
elements in all instances. Variations in spelling are not included as synonyms or keywords.
E.g. ORPHA101 Dentatorubropallidoluysian atrophy

Procedural document on Rare disease nomenclature in English. April 2017 – Number 01 9

www.orpha.net/orphacom/cahiers/docs/GB/Disease_naming_rules_in_English_R1_Nom_01.pdf
 ORPHA2346 Angioosteohypertrophic syndrome

iv. Coordinating hyphens

Coordinating hyphens are used to unite word or expressions at the same level in order to create a compound
whose meaning is the addition of the separate element. In the Orphanet nomenclature, this is often used to
create a disease name from a list of signs and symptoms or from a list of eponyms.
E.g. ORPHA261 Emery-Dreifuss muscular dystrophy
ORPHA2668 Nephropathy-deafness-hyperparathyroidism syndrome

v. Suspended hyphens
Suspended hyphens are used when a prefix or first element of a compound is put in common with several
second elements.
E.g. ORPHA280628 Familial progressive hyper- and hypopigmentation

g) Chemical nomenclature
The denomination of chemicals used in rare disease names is based on the interrelated nomenclatures of the
IUPAC and the IUBMB.

h) Gene nomenclature
Gene denomination used in disease names follows the international nomenclature of the HGNC. The
“approved gene symbol” is used in the preferred term, while the « approved gene name » is used in the
synonyms.

i) Protein nomenclature
Protein denomination used in disease names follows the recommendations of the UniProt-KB. When available,
“short name” is used in the preferred term, and the expansion is used in the synonyms. Otherwise,
“Recommended name” is used. “Alternative name” is not used unless it is widely used in the biomedical
literature.

2. General editorial rules

The following rules apply to every cases developed hereafter:
 Commonly used name in biomedical literature are used as preferred term no matter what.
 Actual well-established practice trumps any other editorial rule.
 When there are several competing denominations, their compatibility with internal editorial rules are
assessed to adopt the most appropriate as preferred term.
 When there is no name available from literature, it is attributed by Orphanet in accordance with the
editorial rules.

a) Priority to clinical practice

Diseases in the Orphanet database are defined primarily on a clinical basis. The nomenclature accordingly
follows a primarily clinical logic. Genetic or aetiological considerations can be used secondarily for additional
distinctions.
Diseases are as far as possible are named consistently within the groups of diseases they belong to.

Procedural document on Rare disease nomenclature in English. April 2017 – Number 01 10

www.orpha.net/orphacom/cahiers/docs/GB/Disease_naming_rules_in_English_R1_Nom_01.pdf
 b) Word order
The general rule is that disease names follow the same word order as in normal speech. Qualifiers generally
remain where they are grammatically appropriate.
When the normal word order must be broken, a comma is used to introduce a word group that has been rejected
at the end.
This is most commonly done to introduce disease subtypes (see below in Paragraph G).

c) Latin expressions
The medical vocabulary contains certain Latin expressions used as quotations, often in parallel with English
adaptations. The choice of one of the other possibility is a matter of use, but is consistent across a single group
of diseases. The other possibility is put as synonym.
The Latin spelling and word order is respected and not mixed with the English adaptation.
E.g. ORPHA1463 Triatrial heart Vs Cor triatriatum.

d) Former nomenclatures
When the medical community decides to rename a disease or a group of diseases, the preferred term is changed
to the new consensus name. Former names are nonetheless retained as synonyms.
E.g. ORPHA2982 preferred term: 46,XX disorder of sex development and synonym: Female
pseudohermaphroditism

e) Comparative use of certain words

i. Disease vs. syndrome

Strictly speaking, the word syndrome refers to a recognisable and recurring association of signs, symptoms
and other characteristic morbid features. The word disease means that the underlying cause of this association
is known.
Unfortunately, the medical nomenclature does not use the words syndrome and disease consistently.
In the Orphanet nomenclature, the correct use of those words is followed as far as possible, but the actual use
in medicine has priority even if it is technically incorrect.

ii. Words referring to transmission or acquisition

To refer to a disease that is genetically determined, the words familial, hereditary, genetic, constitutional, non-
acquired tend to be used indiscriminately in disease names. While several may be appropriate in the same
situation, each has a specific meaning and they are not considered as equivalent.
Hereditary is generally used as preferred term. The others are added as synonym only if they are used in the
biomedical literature. Non-acquired is generally avoided since it is a negative characterisation only.

To refer to the lack of familial transmission, the word acquired, sporadic, non-genetic may be found.
Acquired is used by default. Sporadic is generally avoided, since it properly refers to cases, not to diseases.
Non-genetic is generally avoided, since it is a negative characterisation only.

When two forms of a disease are distinguished by the presence or absence of familial transmission, the
opposing terms is by default hereditary vs. acquired or genetic vs. acquired. However, the idiosyncrasies of
some medical specialties are respected:

Procedural document on Rare disease nomenclature in English. April 2017 – Number 01 11

www.orpha.net/orphacom/cahiers/docs/GB/Disease_naming_rules_in_English_R1_Nom_01.pdf
  Acquired vs. non-acquired in endocrinology;
 Constitutional vs. acquired in haematology.

iii. Congenital
A disease is described as congenital when patients are born with the disease or show the signs of the disease
at birth. The word is not used when a person is born with a disease that may not be clinically detectable at once
at birth.

iv. Essential and idiopathic

Strictly speaking, the words essential and idiopathic refer to pathological entities without a known aetiology,
i.e. for which no cause has been found.
For historical reasons, they are often used incorrectly, because the qualifier tends to persist even after the
discovery of an aetiology for a disease formerly described as idiopathic.
For instance, ORPHA656 is called Familial idiopathic steroid-resistant nephrotic syndrome, even if “familial”
is strictly speaking not compatible with “idiopathic” and the causal genes are known.
As far as the usage allows it, those words are used in the correct meaning.

v. Classic and typical

These words are used to differentiate similar diseases, with one (labelled classic or typical) being used as a
prototype because it is more common, better known or was described first. The use of classic or typical follows
the usage in biomedical literature.
When the opposition is between a pair of diseases, the second is usually labelled non-classic or atypical.
The word classic is used rather than classical.

E.g. ORPHA325524 Classic congenital lipoid adrenal hyperplasia due to STAR deficiency
ORPHA325529 Non-classic congenital lipoid adrenal hyperplasia due to STAR deficiency

E.g. ORPHA90038 Typical hemolytic-uremic syndrome

ORPHA2134 Atypical hemolytic-uremic syndrome

vi. Isolated and syndromic

The word isolated is used in the name of diseases when it is necessary to make the precision that they are not
part of a wider syndrome. The word is added even when this is not the case in spoken English: here the need
to avoid ambiguity trumps the accordance with actual usage.
E.g. ORPHA2345 Isolated Klippel-Feil syndrome
ORPHA248340 Isolated delta-storage pool disease

It is sometimes useful to oppose isolated to syndromic, the latter usually naming a group of diseases. These
are the words used by default.
E.g. ORPHA718 Isolated Pierre Robin syndrome
ORPHA138044 Syndromic Pierre Robin syndrome

However, non-syndromic vs. syndromic may also be used if warranted by a dominant actual usage.
E.g. ORPHA87884 Non-syndromic genetic deafness

Procedural document on Rare disease nomenclature in English. April 2017 – Number 01 12

www.orpha.net/orphacom/cahiers/docs/GB/Disease_naming_rules_in_English_R1_Nom_01.pdf
 ORPHA90642 Syndromic genetic deafness

vii. Anomaly, abnormality and malformation

Anomaly is preferred to abnormality in the Orphanet nomenclature.
Malformation is generally avoided.

viii. Defect, deficiency and disability

The following definitions apply to the Orphanet nomenclature:
 Defect refers to a developmental anomaly, a pathological or interrupted process.
 Deficiency refers to the lack or shortage of a functional entity, typically nutrients or endogenously
produced proteins (often enzymes).
 Disability refers to the functional consequences of an impairment: visual, auditive, intellectual etc.

ix. Predisposition and. susceptibility

Orphanet nomenclature follows the predominant usage of predisposition and susceptibility in literature,
consistently within disease groups. Notably, these tendencies are observed:
 Susceptibility tends to be preferred in genetics;
 Susceptibility to infection tends to be preferred in immunology;
 Predisposition to cancer is preferred in oncology.

x. Dwarfism and short stature

Dwarfism (synonym nanism) and short stature have different definitions and are not used indiscriminately.
From Fima Lifshitz (ed.), Pediatric Endocrinology, New York: Informa Healthcare, cop. 2007, vol. 2, ISBN
978-1-420-04270-2. Ch. 1 “Worrisome Growth”, p.1:
Normal ranges in medicine are frequently defines as ± 2 standard deviations (SDs). Thus short stature
can be defined as: (i) height below -2 SD for age and gender within the population or (ii) height more
than -2 SD below the midparental target height. Dwarfism refers to more severe short stature, defined
as height below -3 SD for age and gender norms.
The Orphanet nomenclature follows the definitions given above.

xi. Poisoning and intoxication

Poisoning refers to the symptoms, illness or death produced by a toxic substance in an organism.
Intoxication may refer to poisoning, but also to the lesser state of stimulation, excitement or stupefaction caused
by a psychoactive substance. In this case, it is sometimes used in contrast with poisoning to indicate a milder
disturbance (e.g. alcohol intoxication vs. acute alcohol poisoning).
Poisoning is preferred in the Orphanet nomenclature.

f) Common ways of naming diseases

i. After authors
Author names (eponyms) are commonly used in literature but less informative by themselves than naming
after clinical features. They are therefore avoided as preferred terms, unless actual usage overwhelmingly
prefers eponyms (e.g. ORPHA881 Turner syndrome). Author names remain as synonyms:
E.g. ORPHA1200 Choanal atresia-deafness-cardiac defects-dysmorphism syndrome

Procedural document on Rare disease nomenclature in English. April 2017 – Number 01 13

www.orpha.net/orphacom/cahiers/docs/GB/Disease_naming_rules_in_English_R1_Nom_01.pdf
 Synonym: Burn-McKeown syndrome

When the clinical naming of the disease is not distinctive enough, an eponym is added to ensure the name’s
specificity.
Ex: ORPHA2316 Johnson neuroectodermal syndrome

The following formatting rules apply:

 When there are several eponyms, they are separated by a coordinating hyphen;
 For diseases named after a publication with three authors or less, all of the authors are listed;
 For diseases named after a publication with more than three authors, only the first and last authors of
the publication are included in the disease name.
The Saxon genitive’s is not used after author names, mere juxtaposition is preferred even when the dominant
practice is to use the Saxon genitive. This follows the current tendencies in medical nomenclature and the
editorial choice of the World Health Organization for the ICD-O-3. The rationale is that the physician(s) that
first described the disease neither “owned” it nor suffered from it.
E.g. ORPHA324 Fabry disease

Exceptions can be made to prevent confusions or awkward readings. For instance, ORPHA99672 is called
Fried's tooth and nail syndrome to avoid reading Fried tooth and nail.

Please note that it does not apply to Saxon genitive with common nouns.
E.g. ORPHA97353 Boxer's dementia
ORPHA99906 Farmer's lung disease

ii. After a list of signs and symptoms

The following format is followed:
 Signs and symptoms are separated by coordinating hyphens;
 The word syndrome or disease, according to the situation, is added at the end.
E.g.: ORPHA588 Muscle-eye-brain disease
ORPHA178377 Osteosclerosis-developmental delay-craniosynostosis syndrome

Joining by “and” and “with” is generally avoided, unless this is found in the commonly accepted name of the
disease.
E.g.: ORPHA257 Epidermolysis bullosa simplex with muscular dystrophy
ORPHA2785 Osteopetrosis with renal tubular acidosis

iii. After a pathological process

The disease name starts with the clinical manifestations followed by “due to” and then the process.
E.g. ORPHA34587 Glycogen storage disease due to LAMP-2 deficiency
ORPHA169090 Combined immunodeficiency due to CRAC channel dysfunction

iv. After a gene or a protein – without specified physiopathology

The disease name starts by the gene or protein name, followed by “related” connected by a hyphen. The format
is: [Gene/protein]-related disease.
Procedural document on Rare disease nomenclature in English. April 2017 – Number 01 14
www.orpha.net/orphacom/cahiers/docs/GB/Disease_naming_rules_in_English_R1_Nom_01.pdf
E.g. ORPHA85451 Transthyretin-related familial amyloid cardiomyopathy
ORPHA263463 CHST3-related skeletal dysplasia

v. After another disease (“plus”, “like”, “pseudo”)

As far as possible, this practice is avoided in preferred terms.
According to the formal rules, a hyphen is used to connect the prefix pseudo- to proper names and acronyms,
but fusion is used with common nouns.
E.g. ORPHA1229 Pseudo-TORCH syndrome
ORPHA2978 Chronic intestinal pseudoobstruction

A hyphen is always used to connect -like to a preceding name.

E.g. ORPHA1149 Arthrogryposis-like syndrome

No hyphen or fusion is used to connect plus to a preceding name.

E.g. ORPHA709 Peters plus syndrome

g) Providing contrast between similar diseases

The following rules apply specifically to similarly-named diseases differentiated by an additional precision,
typically numbers, letters, eponyms, clinical specifics, inheritance.
The place of the precisions depends on their number and whether they are used to define a disease as a whole
or several of its subtypes.

When the precision is necessary to define the disease, it is put at the beginning of the name.
E.g. ORPHA70590 Infantile apnea
ORPHA99826 Marburg hemorrhagic fever

When precisions are used to differentiate several subtypes of the same disease, they are put at the beginning
of the name if there is a single precision used as a direct epithet.
E.g. ORPHA314918 Mild Canavan disease
ORPHA314911 Severe Canavan disease

They are rejected to the end of the name when introduced by a dedicated word (“type”, “form”, etc.) or
expression (“due to”, “without” etc.). See afterwards for the selection of the introductory expression.

Rejection at the end is also used when several precisions are added.
E.g. ORPHA308552 Glycogen storage disease due to acid maltase deficiency, infantile onset
ORPHA308573 Glycogen storage disease due to acid maltase deficiency, juvenile onset

i. Identification by numbers or letters

The format is Disease type [number/letter].
For types of disease associated with a number, the number is preferentially in Arabic rather than Roman
numerals.
E.g. ORPHA636 Neurofibromatosis type 1
ORPHA895 Waardenburg syndrome type 2
ORPHA2295 Ehlers-Danlos syndrome type 11

Procedural document on Rare disease nomenclature in English. April 2017 – Number 01 15

www.orpha.net/orphacom/cahiers/docs/GB/Disease_naming_rules_in_English_R1_Nom_01.pdf
If Roman numerals are overwhelmingly used in actual practice, the variant with Arabic numerals is put as
synonym.

E.g. ORPHA1136 Arnold-Chiari malformation type II

ORPHA1136 Arnold-Chiari malformation type 2 (synonym)

For types associated with letters, the letters are capitalised.

E.g. ORPHA77292 Niemann-Pick disease type A

For types associated with a mix of letters and numbers, no space is introduced: the whole type identifier is
treated like an acronym.
E.g. ORPHA93389 Brachydactyly type A5

Numbers added to abbreviations (e.g. CMT1A, LGMD2B, etc.) are written with or without space, with or
without coordinating hyphen, according to dominant usage in literature, but are consistent across the same
group of diseases.

ii. Identification by eponyms

Disease types are frequently identified by eponyms, which are proper names variously referring to the authors
of the first description, a characteristic geographic location, a specific population affected by the disease.
Eponyms used to differentiate types are rejected at the end of the disease name. The format is: Disease,
[Eponym] type.
E.g. ORPHA93302 Brachyolmia, Maroteaux type
ORPHA85448 Familial amyloidosis, Finnish type
ORPHA275 Severe combined immunodeficiency, Athabascan type

iii. Identification by specific involvement

The format is: Disease, [feature] type or Disease, [feature] form, depending of the dominant usage.
E.g. ORPHA286 Ehlers-Danlos syndrome, vascular type
ORPHA254871 Mitochondrial DNA depletion syndrome, hepatocerebral form

iv. Identification by age or severity

Types specified by age or severity follow one of these formats:
 [Age/severity] disease
E.g. ORPHA206436 Infantile Krabbe disease
ORPHA79253 Mild phenylketonuria

 [Age/type]-onset disease

E.g. ORPHA71517 Rapid-onset dystonia-parkinsonism

ORPHA247573 Adult-onset citrullinemia type I

Procedural document on Rare disease nomenclature in English. April 2017 – Number 01 16

www.orpha.net/orphacom/cahiers/docs/GB/Disease_naming_rules_in_English_R1_Nom_01.pdf
 v. Identification by laterality
A number of developmental anomalies have subtypes for unilateral vs. bilateral involvement. The terms for
the subtypes replicate the general term, with an additional qualifier for laterality rejected to the end. The format
is: Anomaly, [unilateral/bilateral].
E.g. ORPHA295036 Congenital patella dislocation
ORPHA295234 Congenital patella dislocation, unilateral
ORPHA295237 Congenital patella dislocation, bilateral

vi. Identification by inheritance

Mentions of inheritance are put at the beginning of the disease name.
E.g. ORPHA99 Autosomal dominant cerebellar ataxia
ORPHA248 Autosomal recessive hypohidrotic ectodermal dysplasia

Dominant and recessive are always preceded by autosomal or X-linked.

X-linked is presumed to be recessive when not mentioned otherwise.

vii. Offensive or shocking names

Some names of diseases, syndromes, signs or symptoms used in the past are now felt as offensive. Some can
also be shocking. Such names are not included in the Orphanet nomenclature.
E.g. ORPHA870 Mongolism is not used for Down syndrome
ORPHA1002 Suicide headache is not used for Cluster headache
ORPHA2440 Lobster-claw deformity is not used for Split hand-split foot malformation

Particular case: the expression mental retardation has not yet disappeared and is kept in keywords. The current
denomination in use is intellectual disability.

h) Acronyms as preferred terms

Acronyms are avoided as preferred terms.
If there is compelling evidence that the developed form is hardly used in literature, the developed name is
always provided as synonym.
E.g. ORPHA136 CADASIL (preferred term)
ORPHA136 Cerebral autosomal dominant arteriopathy with subcortical infarcts and
leukoencephalopathy (synonym)

3. Specific editorial rules

a) Deletions and duplications of chromosomes
If the anomaly is visible on karyotype, the format is:
 Preferred term : Monosomy Nnn or Trisomy Nnn
 Synonyms : Deletion Nnn or Duplication Nnn

If the anomaly is visible only by CGH array, the format is:

 Preferred term : Nnn microdeletion syndrome or Nnn microduplication syndrome
In all cases, the shorthands are added as synonyms, e.g. Del(4)(p16.3), Dup(22)(q11.2)
Procedural document on Rare disease nomenclature in English. April 2017 – Number 01 17
www.orpha.net/orphacom/cahiers/docs/GB/Disease_naming_rules_in_English_R1_Nom_01.pdf
When several bands are involved, there is no hyphen.
E.g. ORPHA96123 Monosomy 22 (preferred term)
ORPHA96123 Deletion 22 (synonym)
ORPHA96123 Del(22) (synonym)
ORPHA250999 2p15p16.1 microdeletion syndrome (preferred term)
ORPHA250999 Del(2)(p15p16.1) (synonym)

b) Metabolic diseases

i. Enzyme deficiencies
For metabolic diseases characterised by either its clinical involvement or the enzyme or the metabolic pathway
deficiency, the preferred term is the most commonly accepted term, no matter whether it is the clinical or the
metabolic one.
E.g. ORPHA818 Smith-Lemli-Opitz syndrome (synonym: 7-dehydrocholesterol reductase deficiency)
ORPHA368 Glycogen storage disease due to muscle glycogen phosphorylase deficiency (synonym:
McArdle disease)

ii. Use of the suffix -emia and -uria

Many metabolic diseases have names referring to elevated blood or urine rates of a characteristic metabolite,
respectively ending in -emia or -uria. When the two are possible, the name in -emia is put as preferred term
and the name in -uria as synonym.

iii. Glycogen storage diseases

Glycogen storage diseases are commonly identified:
 By numbers - but there has been several conflicting numbering patterns;
 By eponyms - but not all have an eponym.
The editorial choice in the Orphanet nomenclature is:
 To use a reference to the enzyme deficiency in the preferred term;
 To put all alternative names as synonyms.
Glycogen storage disease is always preferred to glycogenosis in preferred terms. Glycogenosis is used as
synonym.

iv. Carboxylic acid or carboxylates

Some carboxylic acids are often more commonly mentioned in physiology under their carboxylate anion form:
therefore, aspartate, glutamate, pyruvate are preferred to aspartic acid, glutamic acid, pyruvic acid.
When both forms are found, the dominant use is followed, and the alternative is put as a synonym.

c) Endocrinology
The naming of stimulations and stimulating factors sometimes vacillates between the endings -tropic and -
tropin on one hand (from τρόπος « turn, manner, change ») and -trophic and -trophin on the other hand (from
τροφός « nourishing, nurse »). The Orphanet nomenclature favours the p-forms rather than the ph-forms.
E.g. ORPHA759 Gonadotropin-dependant precocious puberty

Procedural document on Rare disease nomenclature in English. April 2017 – Number 01 18

www.orpha.net/orphacom/cahiers/docs/GB/Disease_naming_rules_in_English_R1_Nom_01.pdf
 d) Infectiology-parasitology
The names of parasitic and fungal infections can end in -iasis or -osis. Theoretically, the -iasis suffix is used
for parasitic diseases and -osis for other infections. This rule is applied, the other variants are put as synonym.

Procedural document on Rare disease nomenclature in English. April 2017 – Number 01 19

www.orpha.net/orphacom/cahiers/docs/GB/Disease_naming_rules_in_English_R1_Nom_01.pdf
 For any questions or comments, please contact us: [email protected]
Editor of this procedural document: Bertrand Bellet and Annie Olry - This procedural document has been approved by: Ana
Rath - Quality control : Charlotte Gueydan
The correct form when quoting this document is :
« Procedural document on rare disease nomenclature in English, Orphanet, April 2017, Number 01:
http://www.orpha.net/orphacom/cahiers/docs/GB/Disease_naming_rules_in_English_R1_Nom_01.pdf