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choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome - Clinical Profile, Genes & Research | Kisho | Kisho

Features include always present findings: Short palpebral fissure; and very common findings: Hypertelorism, Lower eyelid coloboma, Prominent nasal bridge, and Short philtrum. 30 total HPO annotations.

Organ System	Phenotype Count	Example Features
Head and neck	4	Hypomimic face, Cleft palate, Cleft upper lip
Ears	2	Hearing loss (hearing impairment), Conductive hearing impairment
Kidneys and urinary system	2	Renal hypoplasia, Unilateral renal agenesis
Heart and blood vessels	2	Ventricular septal defect, Atrial septal defect
Skin	1	Preauricular skin tag
Growth and development	1	Short stature
Digestive system	1	Feeding difficulties in infancy
Arms and legs	1	2-3 toe syndactyly

GeneReviews

Clinical Guidance

TXNL4A-related craniofacial disorders range from isolated choanal atresia to choanal atresia with minor anomalies to Burn-McKeown syndrome (BMKS), which is characterized by typical craniofacial features (bilateral choanal atresia/stenosis, short palpebral fissures, coloboma of the lower eyelids, prominent nasal bridge with widely spaced eyes, short philtrum, thin vermilion of the upper lip, and prominent ears). Hearing loss is common and cardiac defects and short stature have been reported. Intellectual disability is rare . To date, 20 individuals with biallelic pathogenic variants in TXNL4A have been identified [, , , ]. The following description of the phenotypic features associated with this condition is based on these reports. Table 2. TXNL4A-Related Craniofacial Disorders: Frequency of Select Features

Feature	# of Persons w/Feature / # Assessed	Comment
Bilateral choanal stenosis/atresia	20/20	3 persons have had isolated choanal atresia .

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 TXNL4A-related craniofacial disorder should be suspected in individuals with the following clinical findings and family history. Clinical findings. Bilateral choanal atresia/stenosis WITH OR WITHOUT:

Distinctive facies:
Short palpebral fissures (i.e., distance between inner canthus and outer canthus)
Lower eyelid defects including coloboma and thick eyelashes
Prominent nasal bridge and widely spaced eyes, leading to a typical facial profile
Short philtrum, thin vermilion of the upper lip, thick vermilion of the lower lip, and reduced opening of the mouth
Normal intellect

Family history is consistent with autosomal recessive inheritance (e.g., affected sibs and/or parental consanguinity). Absence of a known family history does not preclude the diagnosis.

Source: GeneReviews — "TXNL4A-Related Craniofacial Disorders"

GeneReviews

Differential Diagnosis

Table 3. Genetic Disorders with Choanal Atresia/Stenosis in the Differential Diagnosis of TXNL4A-Related Craniofacial Disorders

Gene(s)	DiffDx Disorder	MOI	Key Features of DiffDx Disorder	Comment / Distinguishing Features
CHD7	CHARGE syndrome (See CHD7 Disorder.)	AD	Intraocular coloboma, heart defects, choanal atresia, growth deficiency, DD, genital hypoplasia, ear anomalies	While some overlap exists between CHARGE syndrome TXNL4A-related craniofacial disorders, esp choanal atresia, the CHARGE syndrome phenotype comprises clinical findings (intraocular coloboma, genital anomalies, specific ear anomalies) not seen in TXNL4A-related craniofacial disorders.

Genetic testing for TXNL4A 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 choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism 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 a TXNL4A-related craniofacial 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 TXNL4A-Related Craniofacial Disorder

System/Concern	Evaluation	Comment
stenosis/atresia	Airway assessment for evidence of upper-airway obstruction	Esp important in newborns Lower eyelid
defects	Ophthalmology assessment for possible corneal issues	—
Hearing loss	Audiology assessment	Submucous cleft palate or
cleft lip/palate	Cleft palate team assessment	Structural
cardiac defects	Cardiology assessment	Incl echocardiography Genetic
counseling

Source: GeneReviews — "TXNL4A-Related Craniofacial Disorders"

Clinical Trials

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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 TXNL4A-Related Craniofacial Disorder

System/Concern	Evaluation	Frequency
Lower eyelid defects	Ophthalmology eval w/focus on cornea	Per ophthalmologist
Hearing loss	Hearing assessment	Shortly after birth then per audiologist
Craniofacial manifestations	Regular visits to craniofacial team	Per craniofacial team

Source: GeneReviews — "TXNL4A-Related Craniofacial Disorders"

Phenotype severity distribution: 1 always present feature, 4 very common features, 5 common features.

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

Kisho

choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome

Overview

Clinical Presentation

Clinical Guidance

Explore clinical features

Genetic Landscape

Diagnosis

Diagnostic Criteria

Suggestive Findings

Differential Diagnosis

Treatment

Management Guidelines

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Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

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Orphanet

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Questions for Your Care Team

Questions for Your Care Team

choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome

Overview

Clinical Presentation

Clinical Guidance

Explore clinical features

Genetic Landscape

Diagnosis

Diagnostic Criteria

Suggestive Findings

Differential Diagnosis

Treatment

Management Guidelines

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