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

Rare Disease

osteopetrosis

MONDO:0017198

Also known as:Albers-Schonberg diseasemarble bonemarble bone disease

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Overview

Osteopetrosis, also known as marble bone disease, is a descriptive term that refers to a group of rare, heritable disorders of the skeleton characterized by increased bone density on radiographs.

Clinical Trials4 registered · 2 recruiting

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.

No HPO annotations are available for this condition.

GeneReviews

Clinical Guidance

To date, approximately 90 individuals with a pathogenic variant in AMER1 have been reported in the medical literature [; ; Author, personal observation]. The following description of the phenotypic features associated with this condition is based on these reports. Table 2. Osteopathia Striata with Cranial Sclerosis: Frequency of Select Features in Females and Mildly Affected Males

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 osteopathia striata with cranial sclerosis (OS-CS) have been published, however the combination of macrocephaly, cranial sclerosis, and longitudinal metaphyseal striations of the long bones are considered highly characteristic of this condition.

Suggestive Findings

OS-CS should be suspected in individuals with the following clinical and radiographic findings.

Females and Mosaic and/or Mildly Affected Males

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 osteopetrosis. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

No consensus clinical diagnostic criteria for osteopathia striata with cranial sclerosis (OS-CS) have been published. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with OS-CS, 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 Osteopathia Striata with Cranial Sclerosis

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 Osteopathia Striata with Cranial Sclerosis

System/Concern | Evaluation | Frequency

Musculoskeletal

| Clinical assessment for scoliosis joint contractures | Annually or as indicated

Hearing

| Audiology eval

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.

4 clinical trials registered, 2 recruiting. Interventions under study include biologic therapy, drug therapy, other interventions, and gene therapy. Pipeline includes 1 PHASE2, 2 PHASE1. Research is sponsored by a mix of industry and academic institutions.

126 publications have been identified in PubMed for osteopetrosis. Research spans Case Report / Case Series (45%), Basic Science / Preclinical (28%), and Review / Meta-Analysis (9%).

Research Type	Count	% of Total
Patient case studies	55

Data assembled from 5 of 12 sources · Last updated Sep 18, 2026, 5:07 AM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

Orphanet

European rare disease database

Orphanet:2781

GARD

Genetic and Rare Diseases Info Center

GARD:4155

Questions for Your Care Team

→Are any of the 4 active clinical trials a good fit for my situation?
→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

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Feature	% of Persons w/Feature1	Comment
Cranial sclerosis	100%	—
Sclerosis of long bones	100%	—
Metaphyseal striations	~95%	In females mosaic males; not seen in constitutional males
Characteristic facial features	~90%	Frontal bossing, hypertelorism, epicanthal folds, depressed nasal bridge
Macrocephaly	~80%	Absolute or relative macrocephaly
Orofacial clefting	~50%	Cleft palate or cleft lip and palate
Hearing loss	~50%	Conductive /or sensorineural
Mild developmental delays	~30%	Severe developmental delay is rare.
Congenital heart disease	~25%	—
Wilms tumor2	~5%3	Additional malignancies reported: hepatoblastoma, adult-onset colorectal cancer, adult-onset ovarian cancer 1.

GeneReviews

Differential Diagnosis

Females and mildly affected males. Disorders that may present with sclerotic bone disease similar to that observed in females (and mildly affected males) with osteopathia striata with cranial sclerosis (OS-CS) are summarized in . See also the Nosology of Genetic Skeletal Disorders: 2023 Revision, Group 24 – Osteopetrosis and related osteoclast disorders and Group 25 – Osteosclerotic disorders for a review of additional disorders that may be considered in the differential diagnosis of OS-CS. Males with a severe phenotype present with a multiple-malformation syndrome, usually without metaphyseal striations, making the differential diagnosis very broad. AMER1 should be included within the gene list for any fetal or neonatal multiple-malformation presentation. Table 3. Genes of Interest in the Differential Diagnosis of Osteopathia Striata with Cranial Sclerosis

Gene(s)	DiffDx Disorder	MOI	Clinical Features of DiffDx Disorder
Craniometaphyseal dysplasia, autosomal dominant	AD	Bony sclerosis of cranial bones	Metaphyseal flaring; Absence of metaphyseal striations CA2 CLCN7 LRP5 OSTM1 PLEKHM1 SNX10 TCIRG1 TNFRSF11A
TNFSF11	Osteopetrosis1 (OMIM PS259700 PS607634)	ARAD	Bony sclerosis of cranial and long bones
GJA1	Craniometaphyseal dysplasia, autosomal recessive (OMIM 218400)	AR	Bony sclerosis of cranial bones
LRP4	Sclerosteosis 2 (OMIM 614305)	ADAR	Bony sclerosis
PORCN	Focal dermal hypoplasia (Goltz syndrome)	XL	Metaphyseal striations
SOST	Endosteal hyperostosis, van Buchem type (van Buchem disease) (See SOST-Related Sclerosing Bone Dysplasias.)	AR	Bony sclerosis
Hyperphosphatasemia Craniodiaphyseal dysplasia (OMIM 122860)	AD	Bony sclerosis; progressive overgrowth of craniofacial bones w/cranial nerve entrapment	Absence of metaphyseal striations; Diaphyses of long bones expanded within the cortices
Choanal stenosis a common complication Sclerosteosis (See SOST-Related Sclerosing Bone Dysplasias.)	AR	Bony sclerosis	Absence of metaphyseal striations; 2-3 finger syndactyly, nail dysplasia
TGFB1	Camurati-Engelmann disease (progressive diaphyseal dysplasia)	AD	Bony sclerosis of cranial and long bones

Source: GeneReviews — "Osteopathia Striata with Cranial Sclerosis"

System/Concern	Evaluation	Comment
Musculoskeletal	Skeletal survey – long bones skull	To assess for sclerosis /or metaphyseal striations Clinical assessment for scoliosis joint contractures
ENT	ENT assessment	To assess for orofacial clefting
Hearing	Hearing assessment	To evaluate hearing loss
Eyes	Ophthalmology assessment	To evaluate for optic nerve compression
Constitutional	Growth assessment	To assess for short stature in surviving males (less common in females)
Cognition	Developmental assessment	—
Cardiac	Cardiology assessment incl echocardiography	To assess for structural heart defects in females surviving males
Renal	Renal ultrasound exam	To assess for kidney anomalies in surviving males; To evaluate for nephrogenic rests /or Wilms tumor in females males
Neurology	Neurology assessment incl brain MRI	To assess for CNS anomalies in surviving males
Gastroenterology	Imaging for malrotation performed as clinically indicated	Genetic
counseling	By genetics professionals1	To obtain a pedigree inform affected persons families re nature, MOI, implications of OS-CS in order to facilitate medical personal decision making Family support resources
Treatment of Manifestations in Individuals with Osteopathia Striata with Cranial Sclerosis Manifestation/Concern	Treatment	Considerations/Other
Scoliosis	Management per orthopedic surgeon	—
Joint contractures	PT may be helpful.	—
Orofacial clefting	Management per ENT surgeon	Hearing loss
Vision loss	Management per ophthalmologist	Community support groups for vision loss Surgical management per neurosurgeon should be decided on a case-by-case basis.
Cognition	Early intervention services special education services as indicated	—
Cardiac anomalies	Treatment per cardiologist	Genitourinary
anomalies	Treatment per urologist /or nephrologist	Gastrointestinal
anomalies	Treatment per gastroenterologist /or surgery	Wilms tumor /or
other malignancy	Standard treatment	PT = physical therapy Surveillance Table 6.
Recommended Surveillance for Individuals with Osteopathia Striata with Cranial Sclerosis System/Concern	Evaluation	Frequency
Musculoskeletal	Clinical assessment for scoliosis joint contractures	Annually or as indicated Hearing
Wilms tumor	Abdominal ultrasound	Every 3 mos until age 7 yrs as per Beckwith-Wiedemann syndrome guidelines until OS-CS specific guidelines are established1 1. The association of OS-CS with Wilms tumor has only recently been established .

Kisho

osteopetrosis

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Musculoskeletal

Hearing

Research Landscape

Medical References

External Resources

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Therapies Under Investigation

Clinical Trials

Vision

Cognition

Wilms tumor

Recent Publications

Latest News & Developments

The Application of Cell and Gene-Modified Cell Therapy in the Treatment of Osteopetrosis.

Pediatric Dental Management of a Patient With Infantile Osteopetrosis in Remission: A Clinical Case Report.

osteopetrosis

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Musculoskeletal

Hearing

Research Landscape

Medical References

External Resources

Orphanet

GARD

Subtypes

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Therapies Under Investigation

Clinical Trials

Vision

Cognition

Wilms tumor

Recent Publications

Latest News & Developments

The Application of Cell and Gene-Modified Cell Therapy in the Treatment of Osteopetrosis.

Pediatric Dental Management of a Patient With Infantile Osteopetrosis in Remission: A Clinical Case Report.