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Ankyloblepharon Filiforme Adnatum-Imperforate Anus Syndrome (Aughton-Hufnagle Syndrome)
Overview
Ankyloblepharon filiforme adnatum-imperforate anus syndrome, also referred to as Aughton-Hufnagle syndrome, is an extremely rare developmental malformation syndrome that occurs during embryogenesis. This condition is characterized by a specific constellation of congenital abnormalities affecting multiple organ systems, with the two primary features being eyelid fusion and anal abnormalities.[1][2]
According to Orphanet, a European reference portal for rare diseases and orphan drugs, this syndrome has had no further descriptions in the literature since 1993, making it one of the rarest genetic conditions on record. The condition is catalogued under ORPHA:1074 in the Orphanet database.[1]
Clinical Features
Primary Manifestations
The syndrome is defined by two cardinal features that must be present for diagnosis:
Ankyloblepharon Filiforme Adnatum (AFA)
- Characterized by bands of extensile tissue connecting the margins of the upper and lower eyelids[2][1]
- These fibrous bands can be single or multiple, extending vertically between the eyelids
- The bands typically arise from the “grey line” anterior to the meibomian gland orifices and posterior to the eyelashes[3]
- Can occur unilaterally or bilaterally
- May partially or completely prevent normal eyelid opening
Anal Atresia (Imperforate Anus)
- Complete absence or significant narrowing of the anal opening[2][1]
- Represents a failure of normal embryonic development of the terminal portions of the gastrointestinal tract
- Requires immediate surgical intervention in affected newborns
Associated Anomalies
Patients may additionally present with several other congenital abnormalities:
Orofacial Abnormalities
- Cleft palate – incomplete fusion of the roof of the mouth[1][2]
- May occur with or without cleft lip
- Can significantly impact feeding and speech development
Neurological Complications
- Hydrocephalus – abnormal accumulation of cerebrospinal fluid in the brain[2][1]
- Meningomyelocele – a type of spina bifida where the spinal cord and meninges protrude through a defect in the spine[1][2]
- These neurological complications can significantly impact long-term development and quality of life
Embryological Basis
The syndrome represents a developmental defect during embryogenesis, suggesting that the causative factors interfere with normal fetal development during critical periods:[2][1]
Eyelid Development
- Normal eyelid development involves fusion of the eyelid margins until approximately the fifth month of gestation[4]
- Complete separation may not occur until the seventh month of gestation
- AFA represents a failure of normal apoptosis (programmed cell death) during critical stages of eyelid development[4]
Anal Development
- The anal opening normally forms through a complex process of cloacal septation and membrane breakdown
- Imperforate anus represents a failure of this normal developmental process
Differential Diagnosis
Due to the rarity of this specific syndrome, it must be differentiated from other conditions that may present with similar features:
Isolated Ankyloblepharon Filiforme Adnatum
- Characterized by eyelid bands without associated systemic abnormalities[5]
- Much more common than the syndromic form
- Generally has an excellent prognosis with simple surgical correction
Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate (AEC) Syndrome
- Also known as Hay-Wells syndrome[6][7]
- Caused by mutations in the TP63 gene[7][6]
- Features ankyloblepharon, ectodermal abnormalities, and cleft lip/palate
- Does not typically include imperforate anus
Other Syndromes with Ankyloblepharon
- Edwards syndrome (Trisomy 18) – includes multiple congenital abnormalities[4]
- Popliteal pterygium syndrome – characterized by webbing of lower limbs[4]
- CHANDS syndrome – curly hair, ankyloblepharon, and nail dysplasia[4]
Diagnostic Approach
Clinical Assessment
Given the complexity and multiple system involvement, diagnosis requires:
Immediate Neonatal Evaluation
- Detailed physical examination by an experienced pediatrician[8]
- Assessment of eyelid abnormalities and visual development potential
- Evaluation for anal patency and gastrointestinal function
- Neurological assessment for signs of hydrocephalus or spina bifida
Multidisciplinary Consultation
- Pediatric ophthalmology for eyelid assessment and amblyopia prevention
- Pediatric surgery for anal reconstruction planning
- Neurosurgery if hydrocephalus or meningomyelocele is present
- Genetics consultation for family counseling and recurrence risk assessment
Diagnostic Studies
- Cranial imaging (ultrasound, CT, or MRI) to evaluate for hydrocephalus
- Spinal imaging to assess for spina bifida defects
- Gastrointestinal imaging to evaluate the extent of anal abnormalities
- Genetic testing may be considered, though no specific gene has been identified
Management and Treatment
Surgical Interventions
Eyelid Surgery
- Timing: Should be performed promptly to prevent stimulus deprivation amblyopia[8]
- Technique: Simple division of fibrous bands using scissors[8][4]
- Anesthesia: Can often be performed with topical anesthesia in neonates[8]
- Prognosis: Excellent visual outcomes when performed early
Anal Reconstruction
- Urgency: Requires immediate surgical intervention for survival
- Approach: Varies depending on the specific anatomy and associated abnormalities
- Complexity: May require staged procedures and long-term follow-up
Neurosurgical Interventions
- Hydrocephalus: May require ventriculoperitoneal shunt placement
- Meningomyelocele: Requires closure within 24-48 hours of birth to prevent infection
Supportive Care
- Nutritional support due to feeding difficulties from cleft palate
- Infection prevention especially with open neural tube defects
- Developmental support for potential intellectual disabilities
- Long-term monitoring for complications of multiple system involvement
Prognosis and Outcomes
The prognosis for ankyloblepharon filiforme adnatum-imperforate anus syndrome varies significantly based on:
Favorable Factors
- Isolated eyelid involvement responds excellently to surgical correction
- Absence of major neurological abnormalities improves long-term outlook
- Early intervention for all treatable components
Challenging Factors
- Multiple system involvement increases complexity of care
- Neurological complications (hydrocephalus, spina bifida) may impact development
- Associated cleft palate can affect feeding and speech development
Research and Future Directions
Given the extreme rarity of this condition with no reported cases since 1993, several areas warrant attention:
Genetic Research
- Gene identification – No causative gene has been identified
- Inheritance patterns – Mode of inheritance remains unclear
- Molecular mechanisms underlying the developmental abnormalities
Clinical Studies
- Case series compilation to better characterize the phenotype
- Natural history studies to understand long-term outcomes
- Treatment optimization based on accumulated experience
Family Counseling and Support
Genetic Counseling
- Recurrence risk appears to be low given the lack of reported familial cases
- Prenatal diagnosis may be possible with advanced imaging
- Family planning discussions based on individual circumstances
Support Resources
- Connection with rare disease organizations
- Multidisciplinary care coordination
- Long-term developmental monitoring and support
Conclusion
Ankyloblepharon filiforme adnatum-imperforate anus syndrome (Aughton-Hufnagle syndrome) represents one of the rarest congenital malformation syndromes in medical literature. While the individual components (ankyloblepharon and imperforate anus) are well-understood conditions that can be successfully treated, their co-occurrence with other abnormalities creates a complex syndrome requiring multidisciplinary expertise.
The lack of reported cases since 1993 highlights both the extreme rarity of this condition and the need for continued vigilance in recognizing and reporting such cases. Healthcare providers should maintain awareness of this syndrome, particularly when evaluating newborns with multiple congenital abnormalities involving the eyelids and gastrointestinal system.
Early recognition, prompt surgical intervention for treatable components, and comprehensive supportive care offer the best opportunity for optimal outcomes in affected individuals. Continued research into the underlying genetic and developmental mechanisms may eventually provide insights that benefit not only this rare syndrome but our broader understanding of embryonic development and congenital malformation syndromes.
References
- https://www.orpha.net/en/disease/detail/1074
- https://rarediseases.org/mondo-disease/ankyloblepharon-filiforme-imperforate-anus-syndrome/
- https://opthalmology.medresearch.in/index.php/jooo/article/download/84/134/
- https://www.neonet.ch/application/files/5515/6622/8055/COTM_2013_05.pdf
- https://rarediseases.org/mondo-disease/isolated-ankyloblepharon-filiforme-adnatum/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC7474213/
- https://ijdvl.com/a-de-novo-case-of-ankyloblepharon-ectodermal-defects-cleft-lip-palate-syndrome-with-tp63-mutation-diagnosed-prenatally/
- https://www.nature.com/articles/eye201126
- https://medicine.iu.edu/blogs/rare-disease-research/genetic-detectives-unlock-16-year-mystery
- https://rarediseases.info.nih.gov/diseases/697/ankyloblepharon-filiforme-imperforate-anus-syndrome
- https://chemwatch.net/tr/blog/aughton-hufnagle-syndrome-medical-condition/
- https://rarediseases.org/rare-diseases/adnp-syndrome/
- https://chemwatch.net/da/blog/aughton-hufnagle-syndrome-medical-condition/
- https://health.usnews.com/doctors/david-aughton-818934
- https://medlineplus.gov/genetics/condition/von-hippel-lindau-syndrome/
- https://www.ncbi.nlm.nih.gov/medgen/1666000
- https://thisweekindia.news/13-year-old-boy-with-a-rare-genetic-blood-disorder-cured-at-bgs-gleneagles-global-hospital/
- https://magazine.medlineplus.gov/article/rett-syndrome-an-overview-of-this-rare-genetic-disorder
- https://rarediseases.org/rare-diseases/bardet-biedl-syndrome/
- https://www.malacards.org/card/acromegaloid_facial_appearance_syndrome
- https://pubmed.ncbi.nlm.nih.gov/12503102/
- https://www.e-kjgm.org/journal/view.html?doi=10.5734%2FJGM.2013.10.1.57
- https://www.doximity.com/pub/david-aughton-md
- https://pmc.ncbi.nlm.nih.gov/articles/PMC4869468/
- https://pure.johnshopkins.edu/en/publications/x-linked-dominant-chondrodysplasia-punctata-cdpx2-caused-by-singl-3
- https://doctor.webmd.com/doctor/david-aughton-62de2f10-219b-45cd-9185-b27c5301139d-overview
- https://eyewiki.org/Ankyloblepharon
- https://www.orpha.net/en/disease/detail/1072
- https://ijdvl.com/ankyloblepharon-ectodermal-dysplasia-clefting-syndrome/
- https://ouci.dntb.gov.ua/en/works/7pwWG6j9/
- https://medlineplus.gov/genetics/condition/ankyloblepharon-ectodermal-defects-cleft-lip-palate-syndrome/
- https://www.consultant360.com/exclusive/consultant360/dermatology/ankyloblepharon-filiforme-adnatum
- https://www.orpha.net/en/disease/list/a
