Congenital trigeminal anaesthesia: a rare preventable cause of visual loss in children

Abstract

Congenital trigeminal anaesthesia (CTA) is a rare condition characterised by a congenital deficit involving all or part of the sensory component of the trigeminal nerve in children. It is a heterogeneous condition that can present in isolation or is associated with congenital abnormalities affecting the mesoderm, ectoderm and/or brainstem. The authors report a case of a 4-year-old girl who presented with reduced visual acuity, painless bilateral keratitis and painless non-healing lesions on the face, who was confirmed to have CTA on detailed neurophysiological investigations. She also had associated unilateral renal dysplasia and Duane syndrome. The authors also discuss an up-to-date review of the published cases of CTA in literature, the first of which was reported as early as 1984.

Background

Congenital trigeminal anaesthesia (CTA) is an unusual paediatric disorder. Patients can present to doctors in different specialities with various medical problems, but most commonly they present with painless inflammation or infection of the eyes. Rosenberg first published a review of this condition in 1984 and proposed a classification system, which grouped patients with CTA into three categories.¹ The most common group consisted of patients with isolated CTA who present with only corneal anaesthesia. The other two groups were associated with congenital abnormalities affecting the mesoderm and the brainstem and these present with corneal and facial anaesthesia.

Intact corneal sensation plays a vital role in maintaining the integrity of the corneal epithelium.It is an important mechanism in preventing injury through blink reflex and reflex tearing, and aids the healing of epithelial defects by promoting epithelial cell proliferation. Reduced or absent corneal sensation therefore renders the corneal surface vulnerable to occult injury and delayed healing of established corneal epithelial injuries. Punctate keratitis and epithelial loss occur spontaneously in this condition and requires prompt recognition and aggressive therapy to halt progression to infectious keratitis and corneal perforation. Hence, it is important to recognise this condition to prevent visual loss. Moreover, detection of associated congenital abnormalities is essential to ensure appropriate management and follow-up. There is a need for increased awareness of this condition among different specialties that is, general practitioners, paediatric neurology, ophthalmology, emergency department, paediatric gynaecology renal physicians and dermatology.

Case presentation

A 4-year-old girl presented to the paediatric ophthalmologist with discomfort in the eyes and reduced visual acuity of 3/7.5 (Log Lea symbols). Examination revealed bilateral punctate keratopathy with absent corneal sensation and a left Duane’s syndrome. Treatment was instituted with ocular lubricants and all four puncta were occluded with plugs (figure 1). In the months leading up to presentation, she had been noted to have several painless, non-healing lesions on the bridge of the nose and over her cheeks (figure 2). She often appeared to pick at these lesions and make them bleed. A paediatric dermatologist had identified no cause of these lesions. She did not have similar lesions over her extremities. She was referred to the paediatric neurologist for further review and investigations. On clinical examination, it was found that she had an absent corneal reflex and appeared to have absent sensation to crude touch bilaterally over the face, although it was difficult to be absolutely certain at this age. Peripheral motor and sensory examination was normal. Gait was normal and the rest of the systemic and neurological examination was normal. There was no significant medical history. There were no symptoms or signs in either parent or one female sibling. She had an uneventful birth history and had normal developmental milestones.

Figure 1.

Corneal ulcer in the right eye two weeks after the temporary tarsorrhaphy.

Figure 2.

Non-healing skin lesion on the left cheek.

Investigations

Autonomic sensory neuropathy was suspected initially and detailed autonomic testing (including blood pressure in different postures, an ECG, a sweat test, a histamine injection test) and peripheral nerve conduction studies/electromyography were normal. A MRI scan of her head was also normal. Further detailed neurophysiology testing of the cranial nerves revealed she had no blink response and no reaction to stimulation of the first division of the fifth cranial nerve bilaterally. This confirmed the diagnosis of CTA.

In view of the possible associations with congenital mesenchymal anomalies she had further investigations. A skeletal survey showed a lumbar scoliosis. Abdominal ultrasound confirmed the right renal dysplasia and normal Mullerian structures. A karyotype was normal but no specific genetic investigations were arranged as there are no known gene mutations reported.

Differential diagnosis

Neuroparalytic keratitis has a wide differential diagnosis in adults; it is a rare condition in children.

Treatment

Treatment was continued with ocular lubricants, punctual plugs and protective spectacles. One year later however she re-presented with a painless opacity within the cornea of her right eye noticed by her parents. Examination revealed a 3 mm central ulcer in her right eye with an associated hypopyon. In addition there were four painless lesions over the bridge of her nose and cheek that she continuously picked at. A corneal scrape was undertaken and she was treated aggressively with topical antibiotics, and subsequently a temporary tarsorrhaphy for 2 weeks. The ulcer healed well but left a stromal scar. One year later, she developed another episode of infectious keratitis that responded to prompt treatment with antimicrobials.

The lesions on her face healed spontaneously with topical barrier creams without any significant scars.

Outcome and follow-up

She continues to have regular follow-up with the Opthalmologist and has no residual amblyopia. With improved awareness about this condition, she makes a conscious effort not to pick on her face and has managed to prevent further lesions.

Discussion

CTA is a rare paediatric condition which usually presents with painless keratopathy in a young child and may be mistaken for herpes simplex keratitis. Most children present in infancy or early childhood. One child was diagnosed at 14, but it seems likely that he had been experiencing symptoms for some time before the diagnosis was made.² Cases appear to be mostly sporadic, but they can have an autosomal dominant inheritance pattern as two families have been reported with at least two generations of family members affected.^{3 4} However, no specific genetic mutations have been identified in this diverse group of conditions.

Rosenberg proposed a classification system wherein he divided children with CTA into three distinct groups.¹ Group 1 had isolated CTA. All these patients had loss of corneal sensation, many of them had loss of sensation of the first division of the trigeminal nerve but only one of them had loss of sensation in the second division of the nerve. None had absent sensation of the mandibular division. Of the 46 cases in Rosenberg’s review, 23 were in Group 1. Group 2 included associated mesodermal and ectodermal abnormalities of the head and face such as abnormalities of the external ear, skull, vertebra or face, for example, Moebius syndrome or oculo-auriculo-vertebral dysplasia or abnormalities of the Mullerian tract/urogenital system such as Mullerian duct and renal aplasia-cervico somite dysplasia syndrome.^{2 5} Twenty one of the cases in Rosenberg’s review were in Group 2. Group 3 had CTA with associated abnormalities of the brainstem thought to be due to focal dysgenesis secondary to prenatal injury. Two cases in Rosenberg’s review were in Group 3. A detailed summary of the clinical presentation, associated features, investigations and outcome of all cases published in the literature to date is presented in table 1.^{1–4 6–8}

Table 1.

Summary of cases with congenital trigeminal anaesthesia^{1–4 6–8}

References	Age (Y)/Sex (M/F)	Presenting features	Examination	Investigations	Family history and Rosenberg’s group	Outcome
Author’s case	4/F	Absent corneal sensation, L-sided Duane syndrome, non-healing lesions on bridge of nose and cheeks.	Bilateral punctuate keratopathy.	Autonomic testing – N, MRI – N, NCS – no blink response, no reaction from first division of fifth cranial nerve bilaterally. X-ray – L torticollis, lumbar scoliosis. Abdominal US – R kidney dysplasia.	N Group 1	Punctate plugs. Tarsorrhaphy. Antibiotic eye drops as required.
Rosenberg1	4/M	Recurrent bilateral corneal ulceration and bilateral corneal anaesthesia.	Global developmental delay. Dysmophic facial features. Multiple scars on forehead. Bilateral corneal ulceration. Alternating esotropia. Absent corneal reflexes bilaterally. Absent sensation in first division of TN.	Skeletal survey – N. CT – mild hypoplasia of cerebellar hemispheres and brainstem. Enlarged lateral ventricles. BAEP – N. EEG – N.	NK Group 3	Multiple tarsorrhaphies and patching. Continues to suffer from recurrent ulcers.
Rosenberg1	4/F	Corneal ulcer in R eye and decreased sensation of R cornea.	Global developmental delay. Occipital skull defect, low set and deformed ears. Pectoral muscles hypoplastic bilaterally. Sensation in distribution of first division of TN absent on R and decreased on L. Complete R and partial L facial paralysis.	Audiometric testing – sensorineural hearing loss bilaterally.	NK Group 2	Patching.
Rosenberg1	4/F	Corneal ulcer in R eye and decreased sensation of R cornea.	Global developmental delay. Occipital skull defect, low set and deformed ears. Pectoral muscles hypoplastic bilaterally. Sensation in distribution of first division of TN absent on R and decreased on L. Complete R and partial L facial paralysis.	Audiometric testing – sensorineural hearing loss bilaterally.	NK Group 2	Patching.
Rosenberg1	22 month/F	Congenital R facial palsy. Extropia of L eye and inability to gaze to R.	Extra ocular motility severely affected. With attempted R lateral gaze, no visible movement of either eye past midline. Absent adduction R eye. Marked decrease in sensation of first and second division of TN on R. Corneal sensation absent on R but normal on L. R facial nerve palsy.	CT – N. BAEP – N. EEG – N.	NK Group 2	NK
Hashmi2	14/M	Absence of sensation over L side of face and mouth.	Dense L-sided corneal opacity with vision reduced to counting fingers at 1 metre. Absence of sensation in all three divisions of TN on L side of face.	MRI – N. VEP– R eye N. L eye un-reproducible. SEP – N.	NK Group 1	NK
Hashmi2	3/M	Recurrent eye infections.	Pupil responses N. VA 6/18 bilaterally. Corneal reflexes absent. Bilateral corneal scarring. Sensation to pain in three divisions of TN absent bilaterally.	ERG – N. BAEP – R ear low amplitude response. L ear no response. NCS- N. MRI – N.	NK Group 3	Died age 4 years (accidental drug overdose).
Wong3Sister case 5	2 months/F	Bilateral corneal erosions and bilateral corneal anaesthesia.	Both eyes had central, steady and maintained fixation. Neurological examination – mild bilateral sensorineural hearing loss. Decreased sensation in three branches of TN.	Schirmer test – N. CT – N.	Father – decreased corneal sensation and minimal superficial stromal scarring. Paternal grandmother – decreased corneal sensation. Group 1.	Bilateral 2/3-width tarsorrhaphies and ocular lubrication. VA 20/30 bilaterally. Ocular lubricants given. VA age 10 20/60.
Wong3 sister case 4	3/F	Sterile R corneal ulcer.	Decreased sensation in all distributions of TN, including corneal hypoesthesia. Mild sensorineural hearing loss.	Anterior and posterior segment examination normal.	See above Case 4. Group 1.	Antibiotic ointment and daily use of ocular lubricants and moisture chamber glasses. VA age 13 was 20/30 bilaterally.
Keys4	3/M	Bilateral corneal ulcers and dry eyes.	Bilateral corneal and mid-facial sensation loss.	Schirmer test – decreased tear production.	8-year-old half brother. (See below). 34-year-old father. (See below). Group 1	Topical antibiotics. Lubricants. Punctal occlusion. Medial and lateral tarsorrhaphies. Temporary central tarsorrhaphy.
Keys4	8/M	Red eyes and lack of pain sensation to eyes on trauma. Central corneal ulcer.	Diminished mid-facial, forehead and corneal sensation. Delay in growth and development.	Schirmer test – decreased tear production.	3-year-old half brother (See above). 34-year-old father (See below). Group 1.	Bilateral partial tarsorrhaphies. Antibiotic ointment and patching. Temporary suture tarsorrhaphy.
Keys4	34/M (presented as child)	Recurrent left-sided corneal ulcers.	Visual acuity 20/40. Corneas – diffuse irregular epithelial surface with punctuate defect in right eye and stromal scarring in left. Loss of sensation over forehead and midfacial region.	Schirmer test – decreased tear production. Intradermal histamine response – N. MRI – Bilateral hypoplastic trigeminal nerves.	3-year-old son (See above). 8-year-old son (See above). Group 1.	Bilateral lateral tarsorrhaphies.
Van Bijsterveld6	3/F	Recurrent eye inflammation.	Oval ulcer in R eye below and temporal to centre of cornea. Corneal reflexes absent. Remaining CN and neurological examination N.	Slit lamp examination – membrane of Bowman and stroma slightly infiltrated but intact on R, punctuate epithelial keratitis, epithelial erosions and mild epithelial oedema on L eye. Schirmer test- 30 mm in 3.25 min in R and 2.25 min in L eye.	NK Group 1	Ulcer healed well. The patient kept on methylcellulose drops. VA 20/25 R eye and 20/20 L eye.
Mathen7	7/F	Bilateral recurrent corneal ulceration not responding to conventional treatment.	General examination – short stature, short webbed neck, prognathism, absent dentition. Healed scars on fingers from self-inflicted injury. Bilateral corneal ulcers.	CT- N. NCS –N. Renal US– N. Child had reduced pain sensation all over body with preservation of other sensory modalities.	NK Group 2	Patching and tear substitutes. Arm splinting to avoid self-inflicted injury and promote healing.
Mathen7	7/M	Bilateral recurrent corneal ulceration not responding to conventional treatment.	Global developmental delay. Bilateral corneal ulcers.	CT –N. NCS – N. Renal US – N. Absent sensation to all sensory modalities.	NK Group 2	Patching and tear substitutes. Arm splinting to avoid self-inflicted injury and promote healing.
Mathen7	4/F	Bilateral recurrent corneal ulceration not responding to conventional treatment.	Bilateral corneal ulcers.	CT –N. NCS – N. Renal US – N. Sensory exam- N. Reduced tear film?	NK Group 1	Patching and tear substitutes. Arm splinting to avoid self-inflicted injury and promote healing.
Mathen7	4/M	Bilateral recurrent corneal ulceration not responding to conventional treatment.	Healed scars over lips and face from self-inflicted injury. Absent sensation in all three branches of TN.	CT –N. NCS – N. Renal US – N.	NK Group 1	Patching and tear substitutes. Arm splinting to avoid self-inflicted injury and promote healing.
Villanueva8	6/F	Corneal anaesthesia and decreased VA in L eye.	Diagnosed with Goldenhar syndrome age 2 months. Sensorineural hearing loss L ear. Mild hemifacial asymmetry. Decreased sensation 1st division of L TN. Scoliosis. VA 20/15-3 in R and 20/200 in L.	MRI – L TN and Meckel’s cave absent. Hypoplastic L CNs VII and VIII complex.	NK Group 2	Artificial tears and punctual plug in L inferior punctum inserted. Occlusion therapy of R eye every 2 h using occluder contact lens. VA improved to 20/60 in L eye over 6 months.
Villanueva8	3/M	Amblyopia.	Diagnosed with Goldenhar syndrome. R sided microtia, hypoplastic jaw and thoracic 10 hemivertebrae. VA 20/200 R and 20/50 in the L. R cornea was hypoaesthesic relative to L.	Biomicroscopy – 5 mm limbal dermoid in the inferio-temporal quadrant of R eye. MRI – asymmetry of TN with R smaller than L. R CN VII and VIII mildly hypoplastic.	NK Group 2	Glasses were prescribed. Best VA 20/80 in R and 20/30 in L eye. R cornea continues to be hypaesthesic.

BAEP, brainstem auditory evoked potential; CN, cranial nerves; ERG, electroretinogram; L, left; NCS, nerve conduction studies; N, normal; NK, not known; R, right; SEP, somatosensory evoked potential; TN, trigeminal nerve; US, ultrasound; VEP, visual evoked potential; VA, visual acuity; Y, years.

In the cases published since 1984 (table 1), 11 patients were in Group 1, 5 patients in Group 2 and 2 patients in Group 3.

Rosenberg’s classification of CTA reflects the embryology of the trigeminal nerve.^9–11 The sensory component of the trigeminal nerve originates from the neural crest. The motor root of the trigeminal nerve arises from the ventral part of the developing neural tube and is separate from the sensory nerve.¹² Therefore, the motor function of the trigeminal nerve is intact in this disorder. The neural crest also gives rise to the mesoderm and some of the ectoderm of the first branchial arch.¹³ This explains the association of trigeminal anaesthesia with mesodermal and ectodermal abnormalities of the ear, skull and vertebral spine.

The diagnosis of CTA should be considered in all children with a painless keratopathy, especially if they have other medical problems including facial dysmorphism, skeletal dysplasia, cranial nerve palsies, brainstem signs or developmental delay. Other features include a history of altered sensation in the face and painless lesions or ulceration of the skin in the trigeminal distribution that heals poorly. Children may have been noticed to pick at these lesions to prevent them healing. Formal examination for facial sensation and corneal reflex may be difficult in a young child, however making a diagnosis of CTA is important because the absent trigeminal sensation predisposes the child to both skin and corneal injuries. Parents need to be given information about avoiding situations where corneal injury is more likely to happen and also to be vigilant and seek urgent medical attention if a corneal ulcer is suspected. Preventive treatments can be given such as artificial tears. Sometimes surgical treatments are needed for the keratopathy including punctual plugs, temporary tarsorrhaphy and amniotic membrane grafting.^{3 4 12} Despite this, permanent visual loss may occur. It is important to recognise associated dysmorphism and anomalies associated with this condition and appropriate screening investigations like imaging of the brain and genitourinary tract are recommended.

This case signifies the need for improved awareness of this condition which when recognised on time can prevent significant morbidity including visual loss.

Learning points.

• CTA should be considered in all children presenting with painless keratopathy and/or painless non-healing lesions on the face.

• Children with suspected CTA should be screened for associated mesenchymal, ectodermal and brainstem anomalies.

• This report is to improve awareness of this rare condition by paediatricians, opthalmologists, neurologists, geneticists, emergency department practitioners and general practitioners.

• CTA is a preventable cause of visual loss in children.