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

anophthalmia/microphthalmia-esophageal atresia syndrome - Clinical Profile, Genes & Research | Kisho | Kisho

Features include always present findings: Optic nerve aplasia, Bilateral sensorineural hearing impairment, and Global developmental delay; and very common findings: Anophthalmia. 37 total HPO annotations.

Organ System	Phenotype Count	Example Features
Brain and nerves	4	Specific learning disability, Spastic tetraplegia, Spastic diplegia
Eyes	3	Optic nerve aplasia, Cataract, Optic nerve hypoplasia
Bones and joints	3	Vertebral hypoplasia, Vertebral fusion, Butterfly vertebrae
Hormones	2	Hypogonadotropic hypogonadism, Anterior pituitary hypoplasia
Growth and development	2	Short stature, Postnatal growth retardation
Muscles	2	Low muscle tone (hypotonia), Generalized hypotonia
Ears	2	Bilateral sensorineural hearing impairment, Inner ear hearing loss (sensorineural hearing impairment)
Heart and blood vessels	1	Ventricular septal defect
Head and neck	1	Microcephaly
Digestive system	1	Esophageal atresia

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 The following descriptions are based on these key reports, together with all other published cases and the authors' unpublished data.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

Frequency ofPhenotypic Feature inCase Reports (n=38)	HPO Term	HPO Term Frequency1in Case Reports (n=38)
Highly frequent	Anophthalmia	92 Microphthalmia

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
Tracheoesophageal fistula and/or esophageal atresia
Delayed motor development/ learning disability
Postnatal growth failure
Seizures with gray matter heterotopia
Spasticity, dystonia, or status dystonicus

Source: GeneReviews — "SOX2 Disorder"

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

Genetic testing for SOX2 is available. Testing is considered confirmatory for diagnosis.

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 anophthalmia/microphthalmia-esophageal atresia syndrome. 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

System/Concern	Evaluation	Comment
Constitutional	Measurement of weight, length/height, head circumference	Assess for growth failure.
Eyes	Complete ophthalmologic exam by experienced pediatric ophthalmologist	Incl best corrected visual acuity, assessment of refractive error, fundus exam; Consider referral to ophthalmo-plastic surgeon for children w/anophthalmia extreme microphthalmia.
Brain malformation	High-resolution cranial MRI	W/attention to brain/pituitary malformations, optic nerve/chiasm/tract; Mesial temporal heterotopia is highly assoc w/future epilepsy. Anterior pituitary
hypoplasia	Endocrine eval	Assess:; Growth hormone thyroid function;; Gonadotropins (when age appropriate).
Genitourinary	Males: Assessment for micropenis /or cryptorchidism	Consider referral to urologist for cryptorchidism or other genital malformations. Females: Consider pelvic ultrasound exam /or MRI, particularly in pubertal or postpubertal females.
DD/ID	Developmental assessment	Incl motor, adaptive, cognitive, speech/language eval; Eval for early intervention/ special education
Seizures	Neurologic exam	Incl EEG
Spasticity	Neurologic exam	Referral to OT/PT to assess:; Gross motor fine motor skills; Mobility, ADL, need for adaptive devices; Need for ongoing PT (to improve gross motor skills) /or OT (to improve fine motor skills)
Dystonia	Neurologic history exam	Assess axial peripheral tone to advise on likely efficacy of antispasmodic medications procedures.
Hearing loss	Audiologic eval	Assess for sensorineural conductive hearing loss. Esophageal atresia ± tracheoesophageal
fistula	Focused neonatal assessment	These major malformations constitute a surgical emergency.
Genetic counseling	By genetics professionals1	To inform affected persons their families re nature, MOI, implications of SOX2 disorder to facilitate medical personal decision making Family support/ resources
Treatment of Manifestations in Individuals with SOX2 Disorder Manifestation/Concern	Treatment	Considerations/Other
DD/ID	See .	Referral to physiotherapist if evidence of motor impairment Anophthalmia/
Microphthalmia	Early referral to an experienced multidisciplinary team	Prostheses: Consider optically clear expanders to stimulate growth of the orbit periorbital tissues.; Community vision services through early intervention or school district Anterior pituitary
hypoplasia	Hormone replacement by pediatric endocrinologist	Hypogonadotropic
hypogonadism	Hormone replacement prior to expected onset of puberty by pediatric endocrinologist	—
Seizures	Standardized treatment w/ASM by experienced neurologist	Education of parents/caregivers1
Spasticity	Orthopedist/ physical medicine rehab/ PT/OT incl stretching to help avoid contractures falls	Consider need for positioning mobility devices disability parking placard. Dystonia / Status
dystonicus	PT, hydration, intensive care	Dystonia may worsen can show acute change to status dystonicus, which should be considered a medical emergency.
Hearing loss	Hearing aids may be helpful per audiologist/otolaryngologist.	Community hearing services through early intervention or school district Esophageal atresia ± tracheoesophageal
fistula	Perinatal surgery	This constitutes a surgical emergency. ASM = anti-seizure medication; DD = developmental delay; ID = intellectual disability; OT = occupational therapy; PT = physical therapy 1. Education of parents/caregivers regarding common seizure presentations is appropriate.

Source: GeneReviews — "SOX2 Disorder"

GeneReviews

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "SOX2 Disorder"

Clinical Trials

View trials for anophthalmia/microphthalmia-esophageal atresia syndrome

Explore Trials

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	Evaluation	Frequency
Constitutional	Height, weight, head circumference	Every 3-6 mos during childhood Anophthalmia/
Microphthalmia	MRI, assessment of vision, ophthalmologic eval	Every 3-6 mos during childhood w/MRI only if change in clinical status, e.g., sudden change in light-dark or color perception Follow-up eval w/ophthalmo-plastic surgeon
Brain malformation	Neurologic eval	Repeat MRI if change in neurologic status. Anterior pituitary
hypoplasia	Pituitary axis endocrine eval	Every 3-6 mos Hypogonadotropic
hypogonadism	Gonadotropin endocrine eval	Infancy, mid-childhood, then every 3-6 mos from age 8 yrs Developmental delay/
Intellectual disability	Neurodevelopmental assessment	Annually for 1st 5 yrs Monitor school progress.
Seizures	EEG, brain MRI	If change in seizure frequency or type
Spasticity	By OT/PT	Every 3-6 mos during childhood or w/any progression of symptoms or signs, or deteriorating function Dystonia/ Status dystonicus
Sensorineural hearing loss	Audiogram	Annually
Esophageal atresia ± tracheoesophageal fistula	Per treating pediatric surgeon	Per treating pediatric surgeon OT = occupational therapist; PT = physical therapist

Source: GeneReviews — "SOX2 Disorder"

Phenotype severity distribution: 3 always present features, 1 very common feature, 1 common feature.

Estimated prevalence: <1 in 1,000,000 (VERY_RARE).

Kisho

anophthalmia/microphthalmia-esophageal atresia syndrome

Overview

Clinical Presentation

Clinical Guidance

Explore clinical features

Genetic Landscape

Clinical Guidance

Penetrance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Differential Diagnosis

Treatment

Management Guidelines

Therapies Under Investigation

Clinical Trials

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

anophthalmia/microphthalmia-esophageal atresia syndrome

Overview

Clinical Presentation

Clinical Guidance

Explore clinical features

Genetic Landscape

Clinical Guidance

Penetrance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Differential Diagnosis

Treatment

Management Guidelines

Therapies Under Investigation

Clinical Trials

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