Bjornstad syndrome

Summary

Bjornstad syndrome (MONDO:0009872) is a disease caused by BCS1L (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: BCS1L (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 128
• Phenotypes (HPO): 12

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		33	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

12 HPO clinical features (Orphanet curated; top 12 by frequency):

HPO ID	Term	Frequency
HP:0000407	Sensorineural hearing impairment	Very frequent (80-99%)
HP:0001596	Alopecia	Very frequent (80-99%)
HP:0002231	Sparse body hair	Very frequent (80-99%)
HP:0002299	Brittle hair	Very frequent (80-99%)
HP:0003777	Pili torti	Very frequent (80-99%)
HP:0100840	Aplasia/Hypoplasia of the eyebrow	Very frequent (80-99%)
HP:0000035	Abnormal testis morphology	Frequent (30-79%)
HP:0000478	Abnormality of the eye	Frequent (30-79%)
HP:0002213	Fine hair	Frequent (30-79%)
HP:0008736	Hypoplasia of penis	Frequent (30-79%)
HP:0000135	Hypogonadism	Occasional (5-29%)
HP:0001249	Intellectual disability	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Bjornstad syndrome
Mondo ID	MONDO:0009872
MeSH	C537633
OMIM	262000
Orphanet	123
DOID	DOID:0050677
UMLS	C0266006
MedGen	82728
GARD	0000022
NORD	859
Is cancer (heuristic)	no

Also known as: Bjornstad syndrome · BJS · Björnstad Syndrome · deafness and pili torti, Bjornstad type · deafness-pili torti-hypogonadism syndrome · pili torti-sensorineural hearing loss · PTD · PTND

Data availability: 128 ClinVar variants · 6 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › Bjornstad syndrome

Related subtypes (218): immunodeficiency-centromeric instability-facial anomalies syndrome, hypercalcemia, infantile, Ochoa syndrome, autosomal recessive Ehlers-Danlos syndrome, vascular type, hydrolethalus syndrome, 3-M syndrome, isolated hyperchlorhidrosis, dacryocystitis-osteopoikilosis syndrome, Hutchinson-Gilford progeria syndrome, achalasia microcephaly syndrome, acrorenal syndrome, autosomal recessive, beta-ketothiolase deficiency, autosomal recessive Alport syndrome, Alstrom syndrome, microphthalmia with limb anomalies, camptodactyly-arthropathy-coxa vara-pericarditis syndrome, Behr syndrome, bifid nose, autosomal recessive, Bloom syndrome, Bowen-Conradi syndrome, camptodactyly with fibrous tissue hyperplasia and skeletal dysplasia, heart defects-limb shortening syndrome, autosomal recessive palmoplantar keratoderma and congenital alopecia, COFS syndrome, craniometaphyseal dysplasia, autosomal recessive, Fraser syndrome, cystic fibrosis, polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly, persistent hyperplastic primary vitreous, autosomal recessive, Donnai-Barrow syndrome, Schöpf-Schulz-Passarge syndrome, cleft lip/palate-ectodermal dysplasia syndrome, Ellis-van Creveld syndrome, Wolcott-Rallison syndrome, autosomal recessive faciodigitogenital syndrome, acromesomelic dysplasia 2B, brittle cornea syndrome, triple-A syndrome, autosomal recessive humeroradial synostosis, multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome, hydrocephalus, nonsyndromic, autosomal recessive 1, autosomal recessive hydrocephalus due to congenital stenosis of aqueduct of Sylvius, hypertelorism, microtia, facial clefting syndrome, hypoparathyroidism-retardation-dysmorphism syndrome, Vici syndrome, Johanson-Blizzard syndrome, autosomal recessive Kenny-Caffey syndrome, Papillon-Lefevre disease, Haim-Munk syndrome, Laurence-Moon syndrome, Donohue syndrome, lipase deficiency, combined, autosomal recessive familial Mediterranean fever, thiamine-responsive megaloblastic anemia syndrome, cartilage-hair hypoplasia, Nijmegen breakage syndrome, pseudo-TORCH syndrome, Galloway-Mowat syndrome, mulibrey nanism, myotonia congenita, autosomal recessive, Schwartz-Jampel syndrome, proteosome-associated autoinflammatory syndrome, Netherton syndrome, Niemann-Pick disease type A, oculodentodigital dysplasia, autosomal recessive, odonto-onycho-dermal dysplasia, autosomal recessive omodysplasia, osteoporosis-pseudoglioma syndrome, Shwachman-Diamond syndrome, phenylketonuria, Laron syndrome, autosomal recessive polycystic kidney disease, autosomal recessive inherited pseudoxanthoma elasticum, autosomal recessive multiple pterygium syndrome, rapadilino syndrome, short-rib thoracic dysplasia 9 with or without polydactyly, autosomal recessive Robinow syndrome, Sjogren-Larsson syndrome, scapuloperoneal spinal muscular atrophy, autosomal recessive, spondyloepiphyseal dysplasia tarda, autosomal recessive, inherited threoninemia, Pendred syndrome, autosomal recessive spondylocostal dysostosis, Werner syndrome, ABCD syndrome, Naxos disease, autosomal recessive amelia, human HOXA1 syndromes, sickle cell disease, autosomal recessive proximal renal tubular acidosis, hyper-IgM syndrome type 2, temtamy preaxial brachydactyly syndrome, TH-deficient dopa-responsive dystonia, craniosynostosis syndrome, autosomal recessive, Niemann-Pick disease type B, skin fragility-woolly hair-palmoplantar keratoderma syndrome, CoQ-responsive OXPHOS deficiency, familial adenomatous polyposis 2, Pierson syndrome, palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome, cardiomyopathy-hypotonia-lactic acidosis syndrome, PHARC syndrome, Kahrizi syndrome, cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies, congenital prothrombin deficiency, immunodeficiency 31B, dyskeratosis congenita, autosomal recessive 2, dyskeratosis congenita, autosomal recessive 3, Nestor-Guillermo progeria syndrome, leukoencephalopathy with calcifications and cysts, mitochondrial pyruvate carrier deficiency, branched-chain keto acid dehydrogenase kinase deficiency, dyskeratosis congenita, autosomal recessive 5, hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome, alacrima, achalasia, and intellectual disability syndrome, hyperlipoproteinemia, type 1D, microcephaly and chorioretinopathy 2, congenital stationary night blindness 1G, combined oxidative phosphorylation deficiency 29, hypermanganesemia with dystonia 2, growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy, gnb5-related intellectual disability-cardiac arrhythmia syndrome, autosomal recessive spastic paraplegia type 78, autosomal recessive limb-girdle muscular dystrophy, Bardet-Biedl syndrome, autosomal recessive cerebellar ataxia, neuronopathy, distal hereditary motor, autosomal recessive, UV-sensitive syndrome, Ehlers-Danlos syndrome, kyphoscoliotic type 1, Cockayne syndrome, hyperphenylalaninemia due to tetrahydrobiopterin deficiency, leukoencephalopathy-palmoplantar keratoderma syndrome, autosomal recessive hypohidrotic ectodermal dysplasia, Warburg micro syndrome, autosomal recessive primary microcephaly, autosomal recessive progressive external ophthalmoplegia, Meier-Gorlin syndrome, autosomal recessive sideroblastic anemia, autosomal recessive intermediate Charcot-Marie-Tooth disease, Perrault syndrome, autosomal recessive hypophosphatemic rickets, de Barsy syndrome, leukocyte adhesion deficiency, Senior-Loken syndrome, autosomal recessive spastic ataxia, childhood-onset autosomal recessive myopathy with external ophthalmoplegia, autosomal recessive cerebral atrophy, GM3 synthase deficiency, autosomal recessive distal renal tubular acidosis, pigmentation defects-palmoplantar keratoderma-skin carcinoma syndrome, autosomal recessive brachyolmia, Aicardi-Goutieres syndrome, homocystinuria without methylmalonic aciduria, Niemann-Pick disease type C, nephronophthisis, autosomal recessive osteopetrosis, peroxisome biogenesis disorder, congenital non-bullous ichthyosiform erythroderma, Seckel syndrome, Usher syndrome, autosomal recessive cutis laxa type 1, autosomal recessive cutis laxa type 2, hearing loss, autosomal recessive, microcephaly, growth restriction, and increased sister chromatid exchange 2, encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1, congenital vertebral-cardiac-renal anomalies syndrome, hair defect with photosensitivity and intellectual disability syndrome, autosomal recessive severe congenital neutropenia, severe combined immunodeficiency due to CARMIL2 deficiency, extraoral halitosis due to methanethiol oxidase deficiency, neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities, mitochondrial complex 2 deficiency, nuclear type 3, mitochondrial complex 2 deficiency, nuclear type 4, mismatch repair cancer syndrome, spondyloepimetaphyseal dysplasia with joint laxity, type 3, Kilquist syndrome, Duane anomaly-myopathy-scoliosis syndrome, autosomal recessive axonal charcot-marie-tooth disease due to copper metabolism defect, immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome, optic atrophy-ataxia-peripheral neuropathy-global developmental delay syndrome, congenital myopathy with reduced type 2 muscle fibers, NAD(P)HX dehydratase deficiency, autosomal recessive ocular albinism, ichthyosis linearis circumflexa, eosinophil peroxidase deficiency, hyperphenylalaninemia due to DNAJC12 deficiency, autosomal recessive epidermolytic ichthyosis, Ehlers-Danlos syndrome, classic-like, 2, joint laxity, short stature, and myopia, HELIX syndrome, auditory neuropathy-optic atrophy syndrome, glycosylphosphatidylinositol biosynthesis defect 15, neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, SCN4A-related myopathy, autosomal recessive, Uner Tan Syndrome, nephropathic cystinosis, Imerslund-Grasbeck syndrome type 1, Imerslund-Grasbeck syndrome type 2, permanent neonatal diabetes mellitus 1, growth hormone insensitivity with immune dysregulation 1, autosomal recessive, Rajab interstitial lung disease with brain calcifications 1, Roberts-SC phocomelia syndrome, neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, RPE65-related recessive retinopathy, GUCY2D-related recessive retinopathy, autosomal recessive titinopathy, intellectual disability, autosomal recessive, ALPL-related autosomal recessive hypophosphatasia, spastic paraplegia 18b, autosomal recessive, CEP164-related ciliopathy, RP1-related recessive retinopathy, pseudohypoaldosteronism, type IB2, autosomal recessive, pseudohypoaldosteronism, type IB3, autosomal recessive, spastic paraplegia 30B, autosomal recessive, cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy 1, brain small vessel disease 2B, autosomal recessive, IMPG1-related recessive retinopathy, PROM1-related recessive retinopathy

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

128 retrieved; paginated sample, class counts are floors:

41 uncertain significance, 32 pathogenic/likely pathogenic, 29 likely pathogenic, 9 conflicting classifications of pathogenicity, 8 pathogenic, 4 likely benign, 3 benign, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1028218	NM_001079866.2(BCS1L):c.696del (p.Gly233fs)	BCS1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1032892	NM_001079866.2(BCS1L):c.642G>A (p.Trp214Ter)	BCS1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071417	NM_001079866.2(BCS1L):c.917G>A (p.Arg306His)	BCS1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072216	NM_001079866.2(BCS1L):c.336G>A (p.Trp112Ter)	BCS1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073784	NM_001079866.2(BCS1L):c.463C>T (p.Arg155Ter)	BCS1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
126497	NM_001079866.2(BCS1L):c.901T>A (p.Tyr301Asn)	BCS1L	Pathogenic	no assertion criteria provided
1350830	NM_001079866.2(BCS1L):c.903C>A (p.Tyr301Ter)	BCS1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1414470	NM_001079866.2(BCS1L):c.493A>T (p.Lys165Ter)	BCS1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1442140	NM_001079866.2(BCS1L):c.703G>C (p.Gly235Arg)	BCS1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1452038	NM_001079866.2(BCS1L):c.478C>T (p.Gln160Ter)	BCS1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1455942	NM_001079866.2(BCS1L):c.340C>T (p.Arg114Trp)	BCS1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1457638	NM_001079866.2(BCS1L):c.916C>T (p.Arg306Cys)	BCS1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
214160	NM_001079866.2(BCS1L):c.205C>T (p.Arg69Cys)	BCS1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
214162	NM_001079866.2(BCS1L):c.871C>T (p.Arg291Ter)	BCS1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
214166	NM_001079866.2(BCS1L):c.325C>T (p.Arg109Trp)	BCS1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2184969	NM_001079866.2(BCS1L):c.793C>T (p.Arg265Ter)	BCS1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2680153	NM_001079866.2(BCS1L):c.1026dup (p.Arg343fs)	BCS1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2680155	NM_001079866.2(BCS1L):c.950_953del (p.Asp317fs)	BCS1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
370247	NM_001079866.2(BCS1L):c.889+1G>T	BCS1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
370387	NM_001079866.2(BCS1L):c.349C>T (p.Arg117Ter)	BCS1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
371015	NM_001079866.2(BCS1L):c.245C>A (p.Ser82Ter)	BCS1L	Pathogenic	criteria provided, multiple submitters, no conflicts
371250	NM_001079866.2(BCS1L):c.556C>T (p.Arg186Ter)	BCS1L	Pathogenic	criteria provided, multiple submitters, no conflicts
374395	NM_001079866.2(BCS1L):c.598C>T (p.Arg200Ter)	BCS1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
554756	NM_001079866.2(BCS1L):c.772del (p.Asp258fs)	BCS1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
555982	NM_001079866.2(BCS1L):c.821del (p.Pro274fs)	BCS1L	Pathogenic	criteria provided, multiple submitters, no conflicts
557160	NM_001079866.2(BCS1L):c.372dup (p.Asp125fs)	BCS1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
56412	NM_001079866.2(BCS1L):c.320+1G>T	BCS1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
6164	NM_001079866.2(BCS1L):c.296C>T (p.Pro99Leu)	BCS1L	Pathogenic	criteria provided, multiple submitters, no conflicts
6167	NM_001079866.2(BCS1L):c.232A>G (p.Ser78Gly)	BCS1L	Pathogenic	criteria provided, multiple submitters, no conflicts
6168	NM_001079866.2(BCS1L):c.133C>T (p.Arg45Cys)	BCS1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 16 · Orphanet: 4 · 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
BCS1L	Definitive	Autosomal recessive	Bjornstad syndrome	16

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BCS1L	Orphanet:123	Björnstad syndrome
BCS1L	Orphanet:1460	Isolated complex III deficiency
BCS1L	Orphanet:254902	Renal tubulopathy-encephalopathy-liver failure syndrome
BCS1L	Orphanet:53693	GRACILE 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
BCS1L	HGNC:1020	ENSG00000074582	Q9Y276	Mitochondrial chaperone BCS1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BCS1L	Mitochondrial chaperone BCS1	Chaperone necessary for the incorporation of Rieske iron-sulfur protein UQCRFS1 into the mitochondrial respiratory chain complex III.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BCS1L	Other/Unknown	no		AAA+_ATPase, ATPase_AAA_core, ATPase_AAA_CS

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
apex of heart	1
body of pancreas	1
metanephros cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BCS1L	279	ubiquitous	marker	body of pancreas, metanephros cortex, apex of heart

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BCS1L	3,789

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
BCS1L	Q9Y276	87.10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
Complex III assembly	1	439.2×	0.012	BCS1L
Protein localization	1	190.3×	0.012	BCS1L
Mitochondrial protein import	1	167.9×	0.012	BCS1L
Respiratory electron transport	1	95.2×	0.014	BCS1L
Aerobic respiration and respiratory electron transport	1	88.5×	0.014	BCS1L
Metabolism	1	11.6×	0.086	BCS1L

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
protein insertion into mitochondrial inner membrane from matrix	1	3370.4×	0.001	BCS1L
mitochondrial respiratory chain complex III assembly	1	1203.7×	0.002	BCS1L
mitochondrial respiratory chain complex IV assembly	1	624.1×	0.003	BCS1L
mitochondrial respiratory chain complex I assembly	1	411.0×	0.003	BCS1L
mitochondrion organization	1	151.8×	0.007	BCS1L

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
BCS1L	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	BCS1L

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)
BCS1L	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.