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

premature ovarian failure 21 - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

premature ovarian failure 21

MONDO:0957216

Overview

GeneticsAutosomal dominant · TP63 (chr 3)

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: Elevated circulating follicle stimulating hormone level and Decreased serum estradiol; and common findings: Secondary amenorrhea, Streak ovary, and Primary amenorrhea. 6 total HPO annotations.

Organ System	Phenotype Count	Example Features
Hormones	3	Secondary amenorrhea, Precocious puberty in females, Primary amenorrhea

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.

TP63 function has not been fully characterized.

Premature ovarian failure 21 is associated with mutations in the TP63 gene on chromosome 3.

GeneReviews

Clinical Guidance

Note: Pathogenic variants have been described on two TP63 isoforms: the TAp63 isoform, encoded by NM_003722.4, and the Np63 isoform, encoded by NM_001114982.1, which is 39 amino acids shorter and has an alternate N-terminal TA domain. See for details. AEC syndrome. All pathogenic variants associated with AEC syndrome occur in either the sterile alpha motif (SAM) domain (82%) or the Np63-specific N-terminal domain (18%). Pathogenic variants in the N-terminal domain that introduce premature termination codons lead to the use of an alternative start codon and to the consequent production of Np63 isoforms lacking the N-terminal domain, which are specifically associated with AEC syndrome.

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

Suggestive Findings

A TP63-related disorder should be suspected/considered in individuals with a combination of the following findings.

Clinical findings

Ankyloblepharon filiforme adnatum
Dermal erosions
Signs of ectodermal dysplasia

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 premature ovarian failure 21. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

No clinical practice guidelines for TP63-related disorders have been published. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with a TP63 -related disorder, 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 TP63-Related Disorder

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 TP63-Related Disorder

System/Concern | Evaluation | Frequency

Hypodontia | Prosthodontic assessment | Per dental specialist

Hearing loss | Audiologic testing | Per audiologist/otolaryngologist

Source: GeneReviews — "TP63-Related Disorders"

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 premature ovarian failure 21.

74 publications have been identified in PubMed for premature ovarian failure 21. Research spans Epidemiology / Natural History (42%), Review / Meta-Analysis (23%), and Basic Science / Preclinical (19%).

Research Type	Count	% of Total
Disease patterns and progression	31	42%

Data assembled from 6 of 12 sources · Last updated Sep 19, 2026, 4:31 AM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

OMIM

Online Mendelian Inheritance in Man

OMIM:620311

Questions for Your Care Team

→Should I pursue genetic testing for TP63, 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

The TP63-related disorders include the overlapping phenotypes summarized in and fully described in the text that follows. Table 2. TP63-Related Disorders: Comparison of Phenotypes by Select Features Feature | TP63-Related Disorder

AEC	ADULT	EEC3	Limb-mammary	SHFM4	Orofacialcleft 8
Ankyloblepharon filiforme adnatum	X	—	—	—	—
Ectodermal dysplasia	X	X	X	—	—
Rare	Hypohidrosis1	X	X	—	—
X	Nail dysplasia	X	X	Mild	X
Sparse hair	X	X	X	—	—
Tooth abnormalities	X	X	X	X	—
Cleft lip/palate	X	—	—	—	—
X	X	—	—	—	—
X Split-hand/foot malformation / syndactyly	X	X	X	X	X
Lacrimal duct obstruction	X	X	X	X	—
Dermal erosions	X	—	—	—	—
Hypopigmentation	X	X	X	—	—
Hypospadias	X	—	—	—	—
X	Trismus	X	Excessive freckling	X	Hypoplastic breasts

Source: GeneReviews — "TP63-Related Disorders"

GeneReviews

Differential Diagnosis

Table 3. Genes of Interest in the Differential Diagnosis of TP63-Related Disorders

TP63-Related Disorder	Differential Diagnosis	Gene/GeneticMechanism	MOI	Overlapping Features	Distinguishing Features
AEC syndrome	Epidermolysis bullosa simplex (EBS)	EXPH5 KRT5 KRT14	—	—	—
TGM5	ARAD	Skin erosions at birth	Erosions in AEC syndrome are typically more superficial not assoc w/formation of bullae.; Nondermatologic features dermatopathology also distinguish EBS from AEC syndrome. Autosomal recessive congenital ichthyosis	ABCA12 ALOX12B ALOXE3 CASP14 CERS3 CYP4F22 LIPN NIPAL4 PNPLA1 SDR9C7 SLC27A4	—
TGM1	AR	Erythroderma w/collodion membrane in newborn period1	AEC is not assoc w/collodion membrane or ichthyosis. Curly hair-ankyloblepharon-nail dysplasia syndrome (CHANDS)(OMIM 214350)	—	—
RIPK4	AR	Ankyloblepharon hair changes	CHANDS typically does not incl significant facial/oral clefting or skin erosions that are virtually universal in AEC syndrome. Cocoon syndrome2	—	—
CHUK	ARAD	Ankyloblepharon, cleft lip/palate, ectodermal dysplasia	Cocoon syndrome is assoc w/hypogammaglobulinemia recurrent infections (features not observed in AEC syndrome)	—	—
SHFM4	SHFM1(OMIM 183600)	—	—	—	—
DLX5	AD	Split-hand/foot malformation	SHFM1 is assoc w/high incidence of hearing loss.; Findings are largely restricted to limbs.	—	—
Dental lacrimal duct abnormalities are seen in 10% of persons.3 SHFM3(OMIM 246560)	10q24 contiguous gene duplication	AD	SHFM3 is not assoc w/lacrimal, dental, or ectodermal abnormalities (beyond nail abnormalities assoc w/developmental defects of the digits).4	—	—
SHFM6(OMIM 225300)	WNT10B5	AR	SHFM6 is not assoc w/lacrimal, dental, or ectodermal abnormalities.	—	—
TP63-related disorders generally	Hypohidrotic ectodermal dysplasia (HED)	EDA EDAR EDARADD	—	—	—
WNT10A	ADARXL	Hypotrichosis, hypohidrosis, hypodontia	Hypohidrosis in HED is severe enough to impair body temperature regulation, a problem not seen in TP63-related disorders.	—	—

Source: GeneReviews — "TP63-Related Disorders"

System/Concern	Evaluation	Comment
Ocular issues	Ophthalmologic eval	Evaluate for ankyloblepharon, lacrimal duct atresia/obstruction, dry eyes, blepharitis. Skin, hair, nail
issues	Dermatologic eval	—
Dental anomalies	Dental prosthodontics evals	Assess for need for implants.
Cleft lip/palate	Eval by multispecialty cleft team	—
Hearing loss	Otolaryngologic eval auditory evoked responses	Breast/nipple
asymmetry	Plastic surgery eval	—
Growth delay	Nutritional eval	Further assessment by gastroenterologist may be needed. Developmental
delay	Developmental assessment	Limb malformations
counseling	By genetics professionals1	To inform affected persons their families re nature, MOI, implications of a TP63-related disorder to facilitate medical personal decision making Family support/ resources
Treatment of Manifestations in Individuals with a TP63-Related Disorder Manifestation/Concern	Treatment	Considerations/Other
Ankyloblepharon filiforme adnatum	These strands of tissue between upper lower eyelids are often small autolyse shortly after birth; larger ones may require surgical separation by ophthalmologist.	—
Lacrimal duct atresia/obstruction	Possible need for probing or surgical intervention per ophthalmologist	—
Dry eyes / blepharitis	Hydrating ocular drops or gels	—
Skin erosions	Gentle wound care periodic, dilute bleach soaks (Dakins solution) to prevent secondary infection	Occlusive dressings should not be used, as they tend to stimulate granulation tissue. Treat secondary infections w/topical or oral antibiotics or antifungal agents when appropriate.
Sparse hair / alopecia	Wigs can be used as desired.	Hypodontia
Cleft lip/palate	Care managed by a multispecialty cleft team	—
Hearing loss	Myringotomy for conductive hearing loss from chronic otitis media	—
Breast/nipple asymmetry	Females: significant breast asymmetry may be corrected w/plastic surgery.	—
Growth delay	Optimization of oral caloric intake	Gastrostomy tube placement may be considered.
Developmental delay	Assessment treatment by developmental pediatrician /or child neuropsychologist	—
Limb malformations	OT hand/foot surgery as needed to optimize function	—
Psychological impact of phenotypic features	Referral for psychological support/counseling as necessary	OT = occupational therapy Surveillance Table 6.

Kisho

premature ovarian failure 21

Overview

Clinical Presentation

Genetic Landscape

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

OMIM

Questions for Your Care Team

Questions for Your Care Team

Clinical Guidance

Explore clinical features

Penetrance

Differential Diagnosis

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Recent Publications

premature ovarian failure 21

Overview

Clinical Presentation

Genetic Landscape

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

OMIM

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Clinical Guidance

Explore clinical features

Penetrance

Differential Diagnosis

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Recent Publications