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syndromic microphthalmia - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

syndromic microphthalmia

MONDO:0016073

Also known as:microphthalmia, syndromicsyndrome associated with microphthalmia

Overview

A microphthalmia that is part of a larger syndrome.

OnsetCONGENITAL

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.

Age of onset: at birth.

GeneReviews

Clinical Guidance

SOX2 disorder comprises a phenotypic spectrum that can include anophthalmia and/or microphthalmia, brain malformations, developmental delay/ intellectual disability, esophageal atresia, hypogonadotropic hypogonadism (manifest as cryptorchidism and micropenis in males, gonadal dysgenesis infrequently in females, and delayed puberty in both sexes), pituitary hypoplasia, postnatal growth delay, hypotonia, seizures, and spastic or dystonic movements. To date, 174 individuals from 157 families have been identified with SOX2 disorder [, , , ]. The following descriptions are based on these key reports, together with all other published cases and the authors' unpublished data. Table 2. Select Features of SOX2 Disorder: Frequency of Human Phenotype Ontology (HPO) Terms

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

SOX2 disorder should be considered in individuals with the following clinical and brain MRI findings and family history.

Clinical findings

Bilateral anophthalmia and/or microphthalmia
Unilateral anophthalmia or microphthalmia
Genital abnormalities. Frequently cryptorchidism and/or micropenis in males (commonly a manifestation of hypogonadotropic hypogonadism); infrequently uterus hypoplasia and ovary or vaginal agenesis in females

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 syndromic microphthalmia. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with SOX2 disorder, the evaluations summarized (if not performed as part of the evaluation that led to diagnosis) are recommended. Table 4. Recommended Evaluations Following Initial Diagnosis in Individuals with SOX2 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 SOX2 Disorder

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 syndromic microphthalmia.

70 publications have been identified in PubMed for syndromic microphthalmia. Research spans Case Report / Case Series (40%), Basic Science / Preclinical (36%), and Review / Meta-Analysis (11%).

Research Type	Count	% of Total
Patient case studies	28	40%

Data assembled from 4 of 12 sources · Last updated Sep 19, 2026, 11:53 AM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

Orphanet

European rare disease database

Orphanet:202948

GARD

Genetic and Rare Diseases Info Center

GARD:20342

Questions for Your Care Team

→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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Frequency ofPhenotypic Feature inCase Reports (n=38)	HPO Term	HPO Term Frequency1in Case Reports (n=38)
Highly frequent	Anophthalmia	92 Microphthalmia
Moderately frequent	Generalized hypotonia	8 Hypoplasia of corpus callosum
Less frequent	Hydrocephalus	5 Delayed puberty

GeneReviews

Differential Diagnosis

Genes associated with ocular manifestations frequently observed in SOX2 disorder (with or without nonocular comorbidities) are summarized in . Table 3. Genes of Interest in the Differential Diagnosis of SOX2 Disorder

Gene	Disorder	MOI	Ocular Phenotype	Other Clinical Features	Comment
ALDH1A3	Isolated microphthalmia 8 (OMIM 615113)	AR	Bilateral microphthalmia /or anophthalmia	DD or autism in ~20% of affected persons	—
BMP4	Syndromic microphthalmia 6 (OMIM 607932)	AD	Bilateral anophthalmia, optic disc aplasia/hypoplasia	Small kidneys/renal cyst, small ears	Comorbidities present in 2 families1
GJA8	Cataract 1 (OMIM 116200)	AD	Bilateral microphthalmia, coloboma, cataract2	None	—
NAA10	Lenz microphthalmia syndrome (OMIM 309800)	XL	Unilateral or bilateral microphthalmia /or anophthalmia	Malformations of the ears, teeth, fingers, skeleton, or genitourinary system; Mild-to-severe ID or DD in ~60% of affected males	Polyadenylation signal variants are assoc w/familial anophthalmia.3
OTX2	OTX2 anophthalmia syndrome (MCOPS5) (OMIM 610125)	AD	Ocular features almost identical to those frequently observed in SOX2 disorder4	Brain features almost identical to those of SOX2 disorder4	Esophageal atresia/tracheo-esophageal fistula dystonia are not assoc w/OTX2 pathogenic variants.
PAX6	PAX6 isolated aniridia (See PAX6-Related Aniridia.)	AD	Bilateral microphthalmia /or coloboma, iris hypoplasia, cataract, lens subluxation5	None	—
RAX	RAX microphthalmia (OMIM 611038)	AR	Bilateral microphthalmia /or anophthalmia	~50% of affected individuals had DD or autism.	—
VSX2(CHX10)	VSX2 microphthalmia (OMIM 142993)	AR	Bilateral microphthalmia /or anophthalmia	None	Affected families are of Middle Eastern ethnicity. AD = autosomal dominant; AR = autosomal recessive; DD = developmental delay; ID = intellectual disability; MCOPS5 = microphthalmia, syndromic 5; MOI = mode of inheritance; XL = X-linked 1. ; Author, unpublished data 2. , 3. 4. 5. ,

Source: GeneReviews — "SOX2 Disorder"

Kisho

syndromic microphthalmia

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

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

Recent Publications

syndromic microphthalmia

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

Orphanet

GARD

Subtypes

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Therapies Under Investigation

Clinical Trials

Recent Publications