Kisho

Kisho is an information platform, not a medical provider. Nothing on this site constitutes medical advice, diagnosis, or treatment recommendations. All content is aggregated from publicly available sources (including ClinicalTrials.gov, PubMed, FDA.gov, and Orphanet) and is provided for informational purposes only. Clinical trial eligibility, treatment decisions, and any health-related actions should always be discussed with a qualified healthcare professional. Kisho does not endorse any specific therapy, organization, or clinical trial. Terms of use · Privacy policy

osteocraniostenosis - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

osteocraniostenosis

MONDO:0011215

Also known as:Osteocraniosplenic syndromegracile bone dysplasiaGCLEB

Overview

A lethal skeletal dysplasia characterized by a cloverleaf skull anomaly, facial dysmorphism, limb shortness, splenic hypo/aplasia and radiological anomalies including thin tubular bones with flared metaphyses and deficient calvarial mineralization.

GeneticsAutosomal dominant · FAM111A (chr 11)

ResearchLimited published research (7 articles)

Clinical Presentation

Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.

Features include always present findings: Short stature, Global developmental delay, and Hypocalcemia; and common findings: Micropenis and Hydrocephalus. 19 total HPO annotations.

Organ System	Phenotype Count	Example Features
Brain and nerves	3	Seizure, Global developmental delay, Hydrocephalus

Genetic Landscape

Assembled from HGNC gene records, ClinGen gene-disease validity evidence, and ClinVar pathogenic variant data. Validity classifications reflect the strength of published evidence linking each gene to this disease.

FAM111A encodes FAM111 trypsin like peptidase A (611 aa). Single-stranded DNA-binding serine protease that mediates the proteolytic cleavage of covalent DNA-protein cross-links (DPCs) during DNA synthesis, thereby playing a key role in maintaining genomic integrity. Highest expression in Cells EBV-transformed lymphocytes (49.7 TPM) and Spleen (46.6 TPM).

Osteocraniostenosis is associated with mutations in the FAM111A gene on chromosome 11.

FAM111A is classified as a druggable target (Protease category) with score 0.0.

GeneReviews

Diagnosis

Drawn from GeneReviews diagnostic guidelines, newborn screening panel status (RUSP), and ClinGen gene-disease validity classifications. Reflects current clinical evidence and consensus where available.

GeneReviews

Diagnostic Criteria

No consensus clinical diagnostic criteria for FAM111A-related skeletal dysplasias have been published.

Suggestive Findings

FAM111A-related skeletal dysplasias include the milder phenotype of Kenny-Caffey syndrome and a more severe lethal phenotype, osteocraniostenosis. A FAM111A-related skeletal dysplasia should be suspected in probands with a combination of the following clinical, imaging, and laboratory findings:

Kenny-Caffey Syndrome

Clinical findings

Treatment

Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.

No approved treatments are currently available for osteocraniostenosis. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

No clinical practice guidelines for FAM111A-related skeletal dysplasias have been published. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with a FAM111A-related skeletal dysplasia, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 4. Recommended Evaluations Following Initial Diagnosis in Individuals with a FAM111A-Related Skeletal Dysplasia

Prognosis

Based on GeneReviews surveillance recommendations, HPO phenotype frequency and severity annotations, and published prevalence estimates from Orphanet and OMIM.

GeneReviews

Surveillance Guidelines

Table 6. Recommended Surveillance for Individuals with a FAM111A-Related Skeletal Dysplasia

System/Concern

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

No clinical trials have been registered for osteocraniostenosis.

7 publications have been identified in PubMed for osteocraniostenosis. Research spans Case Report / Case Series (43%), Basic Science / Preclinical (43%), and Review / Meta-Analysis (14%).

Recent Publications

Hatziagapiou K (2026). [PMID: 41901222](https://pubmed.ncbi.nlm.nih.gov/41901222/). *Pharmaceuticals (Basel)*. [Review / Meta-Analysis]
Zhang L (2026). [PMID: 41663299](https://pubmed.ncbi.nlm.nih.gov/41663299/). *Zhonghua Yi Xue Yi Chuan Xue Za Zhi*. [Case Report / Case Series]
Bonde LD (2025). [PMID: 39501122](https://pubmed.ncbi.nlm.nih.gov/39501122/). *J Hum Genet*. [Basic Science / Preclinical]
Li D (2025). [PMID: 39932783](https://pubmed.ncbi.nlm.nih.gov/39932783/). *JCI Insight*. [Basic Science / Preclinical]
Tan RSG (2024). [PMID: 38697929](https://pubmed.ncbi.nlm.nih.gov/38697929/). *Physiol Rep*. [Basic Science / Preclinical]

Data assembled from 7 of 12 sources · Last updated Sep 19, 2026, 4:29 PM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

OMIM

Online Mendelian Inheritance in Man

OMIM:602361

Orphanet

European rare disease database

Orphanet:2763

GARD

Genetic and Rare Diseases Info Center

GARD:3396

Questions for Your Care Team

→Should I pursue genetic testing for FAM111A, and what would the results mean for my family?
→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

← Back to All Diseases

GeneReviews

Clinical Guidance

FAM111A-related skeletal dysplasias include the milder phenotype of Kenny-Caffey syndrome (KCS) and a more severe lethal phenotype, osteocraniostenosis (OCS). To date, at least 35 individuals have been identified with a FAM111A-related skeletal dysplasia [, , , , , , , , , , , , , , , , , , , ]. The following description of the phenotypic features associated with these conditions are based on these reports. Table 2. FAM111A-Related Skeletal Dysplasias: Comparison of Phenotypes by Select Features Feature | Proportion of Persons w/Feature Kenny-Caffey syndrome(22 reported)1 | Osteocraniostenosis(13 reported)1 Anthropometric

Intrauterine growth deficiency	3/15	9/10
Short stature	19/20	6/6
Microcephaly	4/20	3/4
Craniofacial	Large anterior fontanelle/ delayed anterior fontanelle closure	13/19
Craniosynostosis	3/20	1/1
Frontal bossing or prominent forehead	17/19	4/4
Triangular face	10/15	2/3
Short palpebral fissures	11/18	1/2
Midface retrusion	5/16	1/1
Low-set ears	4/15	4/5
Short nose /or narrow nasal ridge	5/15	4/4
Micrognathia or microretrognathia	10/16	3/3
Skeletal	Cloverleaf-shaped skull	0/22
Decreased skull ossification	3/11	10/10
Slender long bones	3/21	9/9
Cortical thickening of long bones	21/21	7/7
Stenosis of medullary cavity of long bones	21/21	7/7
Flared metaphyses	0/16	9/9
Thin ribs	1/21	4/6
Thoracic hypoplasia	0/19	2/4
Acromicria	2/21	1/1
Fractures	0/21	3/10
Endocrine	Primary hypoparathyroidism w/hypocalcemia hyperphosphatemia	20/22
Ophthalmologic	Microphthalmia	1/19
Refractive errors2	15/18	NA
Papilledema/pseudopapilledema	2/19	NA
Dental	Defective dentition3	8/12
Dental caries	4/11	NA
Loss of secondary dentition	3/10	NA NA = not applicable or insufficient information due to osteocraniostenosis being a perinatally lethal condition 1. , , , , , , , , , , , , , , , , , , , 2. Refractive errors include hyperopia, myopia, and astigmatism.

Source: GeneReviews — "FAM111A-Related Skeletal Dysplasias"

GeneReviews

Differential Diagnosis

Genes of interest in the differential diagnosis of Kenny-Caffey syndrome (KCS) are summarized in . Table 3a. Genes of Interest in the Differential Diagnosis of Kenny-Caffey Syndrome

Gene	Disorder	MOI	Features of Differential Diagnosis Disorder
LRP5	Osteosclerosis (OMIM 144750)	AD	Sclerosis of long bones; Dental manifestations
SOST	SOST-related sclerosing bone dysplasias (incl sclerosteosis van Buchem disease)	AR	Diaphyseal sclerosis; Frontal bossing
TBXAS1	Hematodiaphyseal dysplasia Ghosal (OMIM 231095)	AR	Cortical hyperostosis
TGFB1	Camurati-Engelmann disease (diaphyseal dysplasia Camurati-Engelmann)	AD	Frontal bossing; Sclerosis/ cortical thickening of long bones; Medullary stenosis of long bones
TBCE	Sanjad-Sakati syndrome (OMIM 241410)	AR	Short stature; Delayed anterior fontanelle closure; Frontal bossing/ prominent forehead; Micrognathia; Micropenis/cryptorchidism; Low parathyroid hormone; Hypocalcemia; Medullary stenosis of tubular bones; Thin long bones; Patchy osteosclerosis

Source: GeneReviews — "FAM111A-Related Skeletal Dysplasias"

System/Concern	Evaluation	Comment
Constitutional	Growth assessment incl height, weight, body mass index growth velocity, limb proportions, upper-to-lower body segment proportions	Respiratory
Ophthalmologic	Ophthalmology exam	Eval for refractive errors, microphthalmia, astigmatism, pseudopapilledema, cataract
Dental	Dental assessment	When teeth erupt, preferably by age 2-3 yrs Hematologic
Developmental	Developmental assessment to incl motor, adaptive, cognitive, speech-language eval	In those w/OCS; As needed in those w/KCS; note almost all affected persons had normal development cognition Psychosocial
Genetic counseling	By genetics professionals1	To obtain a pedigree inform affected persons their families re nature, MOI, implications of FAM111A-related skeletal dysplasias to facilitate medical personal decision making Family support resources
Treatment of Manifestations in Individuals with a FAM111A-Related Skeletal Dysplasia Manifestation/Concern	Treatment	Considerations/Other Respiratory disease
Hypocalcemia	Supplemental calcium activated forms of vitamin D (calcitriol or alfacalcidol) per endocrinologist	Hypocalcemic seizure can be present in early neonatal period.; Maintenance of normal serum calcium phosphorus is recommended to minimize risk of developing cataracts intracerebral calcification.
Ophthalmologic	Mgmt of refractive errors cataract per ophthalmologist	—
Dental manifestations	Treatment per dentist /or oral surgeon	Short stature
Scoliosis	Conservative or surgical treatment per orthopedist /or neurosurgeon	In 2 adults w/KCS, severe torticollis scoliosis were managed conservatively.2
Development	Individualized developmental support by allied health clinicians	Psychosocial

Kisho

osteocraniostenosis

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

Clinical Guidance

Explore clinical features

Penetrance

Differential Diagnosis

Clinical Trials

osteocraniostenosis

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

Orphanet

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Clinical Guidance

Explore clinical features

Penetrance

Differential Diagnosis

Clinical Trials