CHILD syndrome

Summary

CHILD syndrome (MONDO:0010621) is a disease caused by NSDHL (GenCC Definitive), with 1 cohort gene and 5 clinical trials. Top therapeutic interventions include lovastatin.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: NSDHL (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 56
• Phenotypes (HPO): 23
• Clinical trials: 5

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		60	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

23 HPO clinical features (Orphanet curated; top 23 by frequency):

HPO ID	Term	Frequency
HP:0010655	Epiphyseal stippling	Very frequent (80-99%)
HP:0000962	Hyperkeratosis	Frequent (30-79%)
HP:0001036	Parakeratosis	Frequent (30-79%)
HP:0007431	Congenital ichthyosiform erythroderma	Frequent (30-79%)
HP:0008394	Congenital onychodystrophy	Frequent (30-79%)
HP:0010049	Short metacarpal	Frequent (30-79%)
HP:0025092	Epidermal acanthosis	Frequent (30-79%)
HP:0031517	Verruciform xanthoma	Frequent (30-79%)
HP:0045060	Aplasia/hypoplasia involving bones of the extremities	Frequent (30-79%)
HP:0100803	Abnormality of the periungual region	Frequent (30-79%)
HP:0012165	Oligodactyly	Occasional (5-29%)
HP:0001627	Abnormal heart morphology	Occasional (5-29%)
HP:0002011	Morphological central nervous system abnormality	Occasional (5-29%)
HP:0002089	Pulmonary hypoplasia	Occasional (5-29%)
HP:0002650	Scoliosis	Occasional (5-29%)
HP:0002828	Multiple joint contractures	Occasional (5-29%)
HP:0003651	Foam cells	Occasional (5-29%)
HP:0004552	Scarring alopecia of scalp	Occasional (5-29%)
HP:0009827	Amelia	Occasional (5-29%)
HP:0000104	Renal agenesis	Very rare (<1-4%)
HP:0000126	Hydronephrosis	Very rare (<1-4%)
HP:0001159	Syndactyly	Very rare (<1-4%)
HP:0010442	Polydactyly	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	CHILD syndrome
Mondo ID	MONDO:0010621
MeSH	C562515
OMIM	308050
Orphanet	139
DOID	DOID:0111822
SNOMED CT	17608003
UMLS	C0265267
MedGen	82697
GARD	0006039
NORD	1284
Is cancer (heuristic)	no

Also known as: child nevus · CHILD syndrome · child syndrome · CHILD syndrome, X-linked dominant · congenital hemidysplasia with ichthyosiform nevus and limb defects · Ichthyosis, CHILD Syndrome · ichthyosis, child syndrome

Data availability: 56 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › musculoskeletal system benign neoplasm › benign connective and soft tissue neoplasm › bone benign neoplasm › CHILD syndrome

Related subtypes (18): bone ameloblastoma, phalanx chondroma, ossifying fibroma, periosteal chondroma, chondroblastoma, osteoma, paranasal sinus Schneiderian papilloma, osteoid osteoma, chondromyxoid fibroma, craniopharyngioma, osteoblastoma, benign neoplasm of pituitary gland, benign neoplasm of sphenoidal sinus, benign neoplasm of frontal sinus, benign neoplasm of maxillary sinus, benign neoplasm of ethmoidal sinus, benign neoplasm of lower jaw bone, desmoplastic fibroma

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

ClinVar germline variants

56 retrieved; paginated sample, class counts are floors:

19 uncertain significance, 10 pathogenic, 10 conflicting classifications of pathogenicity, 8 benign/likely benign, 5 likely pathogenic, 2 benign, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
11427	NM_015922.3(NSDHL):c.613G>A (p.Gly205Ser)	NSDHL	Pathogenic	no assertion criteria provided
11428	NM_015922.3(NSDHL):c.628C>T (p.Gln210Ter)	NSDHL	Pathogenic	no assertion criteria provided
11429	NM_015922.3(NSDHL):c.262C>T (p.Arg88Ter)	NSDHL	Pathogenic	no assertion criteria provided
11430	NM_015922.3(NSDHL):c.544G>C (p.Ala182Pro)	NSDHL	Pathogenic	no assertion criteria provided
11431	NM_015922.3(NSDHL):c.451G>T (p.Glu151Ter)	NSDHL	Pathogenic	no assertion criteria provided
159454	NM_015922.3(NSDHL):c.757C>T (p.Gln253Ter)	NSDHL	Pathogenic	criteria provided, single submitter
159456	NM_015922.3(NSDHL):c.904del (p.Tyr302fs)	NSDHL	Pathogenic	criteria provided, single submitter
159457	NM_015922.3(NSDHL):c.906C>A (p.Tyr302Ter)	NSDHL	Pathogenic	criteria provided, single submitter
211748	NM_015922.3(NSDHL):c.1038_1041dup (p.Gly348fs)	NSDHL	Pathogenic	criteria provided, single submitter
4082153	G50R	NSDHL	Pathogenic	no assertion criteria provided
11426	NM_015922.3(NSDHL):c.314C>T (p.Ala105Val)	NSDHL	Likely pathogenic	criteria provided, single submitter
159449	NM_015922.3(NSDHL):c.1114del (p.Val372fs)	NSDHL	Likely pathogenic	criteria provided, single submitter
21265	NM_015922.3(NSDHL):c.1046A>G (p.Tyr349Cys)	NSDHL	Likely pathogenic	criteria provided, single submitter
2441794	NM_015922.3(NSDHL):c.387del (p.Ile129fs)	NSDHL	Likely pathogenic	criteria provided, single submitter
800901	NM_015922.3(NSDHL):c.317C>T (p.Ser106Leu)	NSDHL	Likely pathogenic	criteria provided, single submitter
1336685	NM_015922.3(NSDHL):c.265C>G (p.Gln89Glu)	NSDHL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1501081	NM_015922.3(NSDHL):c.790-9T>A	NSDHL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
159452	NM_015922.3(NSDHL):c.595C>T (p.Arg199Cys)	NSDHL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
159453	NM_015922.3(NSDHL):c.727G>A (p.Val243Met)	NSDHL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1800569	NM_015922.3(NSDHL):c.796C>T (p.His266Tyr)	NSDHL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2026762	NM_015922.3(NSDHL):c.544-3C>T	NSDHL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2052304	NM_015922.3(NSDHL):c.842G>T (p.Arg281Leu)	NSDHL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3301142	NM_015922.3(NSDHL):c.19G>A (p.Glu7Lys)	NSDHL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3598149	NM_015922.3(NSDHL):c.656C>T (p.Ala219Val)	NSDHL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3598157	NM_015922.3(NSDHL):c.1100G>A (p.Arg367His)	NSDHL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1055356	NM_015922.3(NSDHL):c.1037C>G (p.Ala346Gly)	NSDHL	Uncertain significance	criteria provided, multiple submitters, no conflicts
1297520	NM_015922.3(NSDHL):c.947C>G (p.Pro316Arg)	NSDHL	Uncertain significance	criteria provided, single submitter
1311669	NM_015922.3(NSDHL):c.263G>A (p.Arg88Gln)	NSDHL	Uncertain significance	criteria provided, multiple submitters, no conflicts
1361740	NM_015922.3(NSDHL):c.560A>G (p.Asn187Ser)	NSDHL	Uncertain significance	criteria provided, multiple submitters, no conflicts
1468939	NM_015922.3(NSDHL):c.1031A>G (p.Lys344Arg)	NSDHL	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 2 · 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
NSDHL	Definitive	X-linked	CHILD syndrome	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NSDHL	Orphanet:139	CHILD syndrome
NSDHL	Orphanet:251383	CK syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
NSDHL	HGNC:13398	ENSG00000147383	Q15738	Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NSDHL	Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating	Catalyzes the NAD(P)(+)-dependent oxidative decarboxylation of the C4 methyl groups of 4-alpha-carboxysterols in post-squalene cholesterol biosynthesis.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NSDHL	Enzyme (other)	yes	1.1.1.170	3Beta_OHSteriod_DH/Estase, NAD(P)-bd_dom_sf, Lipid_A_modif_metabolic_enz

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adrenal tissue	1
cervix squamous epithelium	1
esophagus mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NSDHL	271	ubiquitous	marker	cervix squamous epithelium, adrenal tissue, esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NSDHL	3,566

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NSDHL	Q15738	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Zymostenol biosynthesis via lathosterol (Kandutsch-Russell pathway)	1	1268.9×	9e-04	NSDHL
Cholesterol biosynthesis via desmosterol (Bloch pathway)	1	1142.0×	9e-04	NSDHL

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
obsolete cholesterol biosynthetic process via lathosterol	1	2106.5×	0.003	NSDHL
labyrinthine layer blood vessel development	1	802.5×	0.004	NSDHL
cholesterol biosynthetic process	1	421.3×	0.004	NSDHL
hair follicle development	1	383.0×	0.004	NSDHL
cholesterol metabolic process	1	195.9×	0.006	NSDHL
smoothened signaling pathway	1	181.2×	0.006	NSDHL

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NSDHL	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
NSDHL	1.1.1.170	3beta-hydroxysteroid-4alpha-carboxylate 3-dehydrogenase (decarboxylating)

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

Druggability pyramid

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

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

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)
NSDHL	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 5.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	4
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01110642	PHASE2	WITHDRAWN	Novel Treatment for Syndromic Ichthyoses
NCT05047354	Not specified	RECRUITING	Biochemical and Phenotypical Aspects of Smith-Lemli-Opitz Syndrome and Related Disorders of Cholesterol Metabolism
NCT07248748	Not specified	RECRUITING	Effects of Alexander Technique in Children With Upper Cross Syndrome.
NCT02383316	Not specified	COMPLETED	Study of Metabolic Modifications in Children With Noonan Syndrome
NCT05131542	Not specified	COMPLETED	Assessment of Hypotonia in Children With Down Syndrome

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LOVASTATIN	4	1