KID syndrome

Summary

KID syndrome (MONDO:0018781) is a disease with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• Phenotypes (HPO): 60

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		100	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

60 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0011496	Corneal neovascularization	Very frequent (80-99%)
HP:0000164	Abnormality of the dentition	Frequent (30-79%)
HP:0000399	Prelingual sensorineural hearing impairment	Frequent (30-79%)
HP:0000491	Keratitis	Frequent (30-79%)
HP:0000509	Conjunctivitis	Frequent (30-79%)
HP:0000572	Visual loss	Frequent (30-79%)
HP:0000613	Photophobia	Frequent (30-79%)
HP:0000653	Sparse eyelashes	Frequent (30-79%)
HP:0000982	Palmoplantar keratoderma	Frequent (30-79%)
HP:0001097	Keratoconjunctivitis sicca	Frequent (30-79%)
HP:0001581	Recurrent skin infections	Frequent (30-79%)
HP:0004552	Scarring alopecia of scalp	Frequent (30-79%)
HP:0005328	Progeroid facial appearance	Frequent (30-79%)
HP:0007431	Congenital ichthyosiform erythroderma	Frequent (30-79%)
HP:0007502	Follicular hyperkeratosis	Frequent (30-79%)
HP:0008070	Sparse hair	Frequent (30-79%)
HP:0008404	Nail dystrophy	Frequent (30-79%)
HP:0008625	Severe sensorineural hearing impairment	Frequent (30-79%)
HP:0011859	Punctate keratitis	Frequent (30-79%)
HP:0025092	Epidermal acanthosis	Frequent (30-79%)
HP:0032107	Limbal stem cell deficiency	Frequent (30-79%)
HP:0040189	Scaling skin	Frequent (30-79%)
HP:0045075	Sparse eyebrow	Frequent (30-79%)
HP:0200020	Corneal erosion	Frequent (30-79%)
HP:0200035	Skin plaque	Frequent (30-79%)
HP:0000966	Hypohidrosis	Occasional (5-29%)
HP:0001369	Arthritis	Occasional (5-29%)
HP:0001508	Failure to thrive	Occasional (5-29%)
HP:0001805	Onychogryposis	Occasional (5-29%)
HP:0003765	Psoriasiform dermatitis	Occasional (5-29%)
HP:0005401	Recurrent candida infections	Occasional (5-29%)
HP:0005406	Recurrent bacterial skin infections	Occasional (5-29%)
HP:0008038	Aplastic/hypoplastic lacrimal glands	Occasional (5-29%)
HP:0008897	Postnatal growth retardation	Occasional (5-29%)
HP:0011370	Recurrent cutaneous fungal infections	Occasional (5-29%)
HP:0012758	Neurodevelopmental delay	Occasional (5-29%)
HP:0025084	Folliculitis	Occasional (5-29%)
HP:0025610	Posterior blepharitis	Occasional (5-29%)
HP:0030318	Angular cheilitis	Occasional (5-29%)
HP:0000230	Gingivitis	Very rare (<1-4%)
HP:0001305	Dandy-Walker malformation	Very rare (<1-4%)
HP:0001320	Cerebellar vermis hypoplasia	Very rare (<1-4%)
HP:0001999	Abnormal facial shape	Very rare (<1-4%)
HP:0002673	Coxa valga	Very rare (<1-4%)
HP:0002860	Squamous cell carcinoma	Very rare (<1-4%)
HP:0003065	Patellar hypoplasia	Very rare (<1-4%)
HP:0006380	Knee flexion contracture	Very rare (<1-4%)
HP:0008069	Neoplasm of the skin	Very rare (<1-4%)
HP:0008138	Equinus calcaneus	Very rare (<1-4%)
HP:0008788	Delayed pubic bone ossification	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	KID syndrome
Mondo ID	MONDO:0018781
MeSH	C536168
OMIM	148210
Orphanet	477
SNOMED CT	2625009
UMLS	C3665333
MedGen	777082
GARD	0003113
MedDRA	10048786
NORD	1326
Is cancer (heuristic)	no

Also known as: ichthyosis hystrix Rheydt type · Keratitis Ichthyosis Deafness Syndrome · keratitis, ichthyosis, and deafness (KID) syndrome · keratitis-ichthyosis-deafness/Hystrix-like ichthyosis-deafness syndrome · KID/HID syndrome · Senter syndrome

Data availability: 2 GenCC gene-disease records.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › keratosis › palmoplantar keratosis › hereditary palmoplantar keratoderma › diffuse palmoplantar keratoderma › KID syndrome

Related subtypes (31): autosomal dominant palmoplantar keratoderma and congenital alopecia, dermatopathia pigmentosa reticularis, Clouston syndrome, epidermolytic palmoplantar keratoderma, 1, palmoplantar keratoderma-deafness syndrome, palmoplantar keratoderma-hereditary motor and sensory neuropathy syndrome, keratosis palmaris et plantaris-clinodactyly syndrome, Bart-Pumphrey syndrome, Naegeli-Franceschetti-Jadassohn syndrome, palmoplantar keratoderma-sclerodactyly syndrome, autosomal recessive palmoplantar keratoderma and congenital alopecia, Schöpf-Schulz-Passarge syndrome, hereditary palmoplantar keratoderma, Gamborg-Nielsen type, Papillon-Lefevre disease, Haim-Munk syndrome, mal de Meleda, odonto-onycho-dermal dysplasia, palmoplantar keratoderma, Bothnian type, diffuse nonepidermolytic palmoplantar keratoderma, loricrin keratoderma, skin fragility-woolly hair-palmoplantar keratoderma syndrome, Curly hair - acral keratoderma - caries syndrome, CEDNIK syndrome, palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome, corneal intraepithelial dyskeratosis-palmoplantar hyperkeratosis-laryngeal dyskeratosis syndrome, hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome, palmoplantar keratoderma, Nagashima type, erythrokeratodermia variabilis, diffuse palmoplantar keratoderma with painful fissures, diffuse palmoplantar keratoderma - acrocyanosis syndrome, hearing loss with skin disease

Subtypes (3): autosomal dominant keratitis-ichthyosis-hearing loss syndrome, ichthyosiform erythroderma, corneal involvement, and hearing loss, ichthyosis, hystrix-like, with hearing loss

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 44 · Orphanet: 11 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
GJB2	Definitive	Autosomal dominant	hearing loss disorder	26
GJB6	Definitive	Autosomal dominant	Clouston syndrome	18

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GJB2	Orphanet:166286	Porokeratotic eccrine ostial and dermal duct nevus
GJB2	Orphanet:2202	Palmoplantar keratoderma-deafness syndrome
GJB2	Orphanet:2698	Knuckle pads-leukonychia-sensorineural deafness-palmoplantar hyperkeratosis syndrome
GJB2	Orphanet:477	KID syndrome
GJB2	Orphanet:494	Keratoderma hereditarium mutilans
GJB2	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
GJB2	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
GJB6	Orphanet:189	Hidrotic ectodermal dysplasia
GJB6	Orphanet:477	KID syndrome
GJB6	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
GJB6	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GJB2	HGNC:4284	ENSG00000165474	P29033	Gap junction beta-2 protein	gencc
GJB6	HGNC:4288	ENSG00000121742	O95452	Gap junction beta-6 protein	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GJB2	Gap junction beta-2 protein	Structural component of gap junctions.
GJB6	Gap junction beta-6 protein	One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GJB2	Other/Unknown	no		Connexin, Connexin26, Connexin_N
GJB6	Other/Unknown	no		Connexin, Connexin_N, Connexin_CS

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gingiva	2
gingival epithelium	2
penis	1
upper arm skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GJB2	196	broad	marker	gingival epithelium, gingiva, penis
GJB6	187	broad	marker	upper arm skin, gingiva, gingival epithelium

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GJB2	1,391
GJB6	1,219

Intra-cohort edges

A	B	Sources
GJB2	GJB6	string_interaction

Structural data

PDB: 1 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GJB2	P29033	24

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GJB6	O95452	82.33

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 2 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Gap junction assembly	2	292.8×	5e-05	GJB2, GJB6
Oligomerization of connexins into connexons	1	1903.3×	7e-04	GJB2
Transport of connexins along the secretory pathway	1	1903.3×	7e-04	GJB2
Transport of connexons to the plasma membrane	1	271.9×	0.004	GJB2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
gap junction-mediated intercellular transport	2	2808.7×	1e-06	GJB2, GJB6
gap junction assembly	2	2106.5×	1e-06	GJB2, GJB6
transmembrane transport	2	168.5×	2e-04	GJB2, GJB6
sensory perception of sound	2	100.9×	3e-04	GJB2, GJB6
cell-cell signaling	2	69.6×	5e-04	GJB2, GJB6
ear morphogenesis	1	2106.5×	0.001	GJB6
sinoatrial node development	1	1053.2×	0.002	GJB6
response to electrical stimulus	1	324.1×	0.005	GJB6
maintenance of blood-brain barrier	1	240.7×	0.006	GJB6
inner ear development	1	187.2×	0.007	GJB6
cellular response to glucose stimulus	1	133.8×	0.009	GJB6
response to lipopolysaccharide	1	62.4×	0.017	GJB6
negative regulation of cell population proliferation	1	21.1×	0.047	GJB6

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 1

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
GJB2	KANAMYCIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GJB2	1	4
GJB6	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
KANAMYCIN	4	GJB2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
GJB2	5	Binding:5

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
KANAMYCIN	4	GJB2

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	GJB2
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	GJB6

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
GJB6	0	GJB2

Clinical trials & evidence

Clinical trials

Clinical trials: 0.