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Year : 2022  |  Volume : 2  |  Issue : 4  |  Page : 955-956

Ophthalmic manifestation of Hereditary Sensory and Autonomic Neuropathy – Five-year follow up

1 Department of Cornea and Refractive Surgery Services, Ratan Jyoti Netralaya, Gwalior, Madhya Pradesh, India
2 Senior Resident, Department of Ophthalmology, Ratan Jyoti Netralaya, Gwalior, Madhya Pradesh, India
3 Department of Vitreoretina and Uvea, Ratan Jyoti Netralaya, Gwalior, Madhya Pradesh, India

Date of Submission12-Jun-2022
Date of Acceptance09-Aug-2022
Date of Web Publication11-Oct-2022

Correspondence Address:
Dr. Praveen Dhanapal
Department of Cornea and Refractive Surgery Services, Ratan Jyoti Netralaya, 18 Vikas Nagar, Gwalior, Madhya Pradesh - 474 002
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijo.IJO_1420_22

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Hereditary Sensory and Autonomic Neuropathy (HSAN) is a rare genetic disorder that usually begins in childhood. It is associated with sensory dysfunction (depressed reflexes, altered pain and temperature perception). We report a case of an orphan and adopted girl child with HSAN type IV masquerading as keratomalacia with normal developmental milestones, absent sensation to pain and temperature, bilateral absent corneal reflexes, corneal xerosis, anhidrosis, and trophic ulcers in both hands and feet.

Keywords: Anhidrosis, CIPA, congenital corneal anesthesia, HSAN, neurotrophic keratitis

How to cite this article:
Dhanapal P, Chaurasia N, Jain A. Ophthalmic manifestation of Hereditary Sensory and Autonomic Neuropathy – Five-year follow up. Indian J Ophthalmol Case Rep 2022;2:955-6

How to cite this URL:
Dhanapal P, Chaurasia N, Jain A. Ophthalmic manifestation of Hereditary Sensory and Autonomic Neuropathy – Five-year follow up. Indian J Ophthalmol Case Rep [serial online] 2022 [cited 2022 Nov 30];2:955-6. Available from: https://www.ijoreports.in/text.asp?2022/2/4/955/358153

Hereditary sensory and autonomic neuropathy (HSAN) is a group of inherited disorders which are associated with sensory dysfunction and varying degrees of autonomic dysfunction. There are five types in the HSAN group. HSAN type IV is congenital insensitivity to pain and anhidrosis (CIPA), which is a rare genetic disorder. Inheritance is autosomal recessive. We report a case of this very rare genetic disease in a 3-year-old orphan and adopted girl child, with ocular features of keratomalacia with a long 5-year follow-up. The diagnosis was based on the clinical features of insensitivity to pain and temperature, anhidrosis, self-mutilating behavior with multiple recurrent oral ulcers, multiple trophic ulcers over joints, and normal intellect. Very few cases of HSAN type IV have been reported so far.[1],[2]

  Case Report Top

A 3-year-old girl child with unknown birth history from central India presented 5 years ago with a complaint of whiteness over the cornea in both eyes, which was associated with redness, watering, minimal pain, and foreign body sensation for 1 month. The degree of pain was not correlating with the ocular signs. No antenatal history was known to the mother as the child was adopted. The child was able to fix and follow the torchlight. On examination, corneal ulcer with melting was present, which gave a keratomalacia-like picture in both eyes. Serum vitamin A levels were noted to be low, for which she was treated with vitamin A therapy. Posterior segment evaluation was not possible due to corneal scar. Ultrasound B scan was normal.

A pediatrician's opinion was sought. The height and weight of the child were appropriate for the age. She had a normal gait and posture and was conscious, alert, and oriented. The patient did not have pain at the site of injuries, nor she was reacting to hot objects. Corneal reflexes were absent. She had trophic ulcers in both feet and hands from previous injuries. The patient had bitten her tongue in the past, and she had disfigurement of lips [Figure 1]. She had two episodes of seizures associated with fever in the past, for which she had been prescribed phenytoin. The rest of the clinical examination was normal. A high degree of HSAN type IV or Lesch Nyhan was considered. Her serum uric acid levels were within normal limits (3.1 mg/dl). A nerve conduction study revealed bilateral S1 radiculopathy. Since HSAN IV affects small nociceptive fibers which may not be detected in the nerve conduction study, the diagnosis of HSAN type IV was made based on clinical presentation.[3] Magnetic resonance imaging (MRI) brain and spinal cord was normal. The child was treated symptomatically and was given offloading shoes for trophic ulcers in the feet. Dressing of the injuries was done. Mother was advised to protect the child from any injuries.
Figure 1: At presentation: (a) trophic ulcers of the foot; (b) mutilated lower lips with oral ulceration and scars; (c) mutilated fingertips with scars

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Over the course of 5 years, there was decreased blink rate with normal lids and lashes and no lagophthalmos in both eyes. The cornea was lusterless with epithelial hypertrophy and scarring, leading to irregular corneal surface in both eyes. [Figure 2]. Schirmer test of the right eye was 1 mm and left eye was 4 mm. Tear film breakup time was found to be below the lower limit (2 s in both eyes). Fluorescein staining showed superficial diffuse punctate keratitis [Figure 2]. Her vision dropped to 3/60 in both eyes along with conjunctival and corneal xerosis. For visual rehabilitation of the child, bilateral punctal occlusion was done. Options of PROSE contact lens, optical iridectomy, and paramedian tarsorrhaphy were recommended, but the mother chose to wait for some time. Therefore, symptomatic treatment with frequent lubricating eye drops and gel were given. These children are at risk of developing amblyopia due to central corneal involvement, and therefore, timely occlusion therapy should be advised. But due to bilateral central corneal involvement, it was not possible in our case.
Figure 2: (a) and (b) Macular grade corneal opacities following resolution of the sterile corneal ulcers in the right and left eye, respectively

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  Discussion Top

HSAN, also known as hereditary sensory neuropathies, includes distinct inherited neurodegenerative disorder that progresses to loss of pain and temperature sensation. HSAN type IV is also known as CIPA. Affected children have markedly decreased ability to sweat. Sweating is the body's way of cooling itself and maintaining a proper temperature. The inability to sweat can cause recurrent episodes of fever. Seizures are sometimes associated with fever episodes. The skin may become abnormally thickened and callused with an exaggeration of normal skin lines (lichenification).

Pain is essential to protect an individual from injury and to alert the body of injury. Children affected with HSAN type IV may suffer repeated injuries and demonstrate behaviors that cause injury to themselves like biting of tips of fingers or toes and tongue and lip. Affected individuals are unable to distinguish between cold and warm stimuli. Treatment options for HSAN type IV are treating the associated comorbidities. However, naloxone is an opioid receptor antagonist and has been shown to lower the thermal and mechanical nociceptive threshold. It has been reported to be of benefit in HSAN type IV, but due to lack of exact dose and details, it was not started in our patient.[4]

Eye abnormalities may develop, specifically neurotrophic keratitis and corneal ulceration leading to corneal scarring. Extraocular and intraocular infections can also occur.[5] Frequent topical lubrication helps to stabilize the ocular surface. Paramedian tarsorrhaphy to prevent corneal exposure and PROSE lens can be considered early in the management to prevent progression of the ocular surface disease. Protective glasses can be prescribed. Optical iridectomy is an option for visual rehabilitation in such patients. The outcomes of keratoplasty are very poor due to absent corneal sensations and chronic ocular surface disease. Affected children are at risk of developing amblyopia, thus timely occlusion therapy should be considered.

Our case was followed up for 5 years. The child initially presented with corneal xerosis and keratomalacia leading to corneal scarring.

  Conclusion Top

Ophthalmic manifestation may be the first presentation in HSAN type IV. A detailed history and general examination helps in diagnosis, appropriate management, and preventing further complications. Parents should be educated about the nature of the disease. Unfortunately, these patients have a very short life span despite appropriate management because of the injuries they suffer.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Suresh B, Reddy V, Kurth I, Jagadeesh S. A child presenting with recurrent corneal ulcers: Hereditary sensory and autonomic neuropathy IV (HSAN IV). Neuroophthalmology 2018;43:310-2.  Back to cited text no. 1
Mantelli F, Nardella C, Tiberi E, Sacchetti M, Bruscolini A, Lambiase A. Congenital corneal anesthesia and neurotrophic keratitis: Diagnosis and management. Biomed Res Int 2015;2015:805876.  Back to cited text no. 2
Zhang S, Malik Shrif S, Chen YC, Valente EM, Ahmed M, Sheridan E, et al. Clinical features for diagnosis and management of patients with PRDM12 Congenital insensitivity to pain. J Med Genet 2016;53:533-5.  Back to cited text no. 3
Kalaskar R, Kalaskar A. Hereditary sensory and autonomic neuropathy type V: Report of a rare case. Contemp Clin Dent 2015;6:103-6.  Back to cited text no. 4
[PUBMED]  [Full text]  
Amano S, Fukuoka S, Usui T, Honda N, Ideta R, Ochiai M, et al. Ocular manifestations of congenital insensitivity to pain with anhidrosis. Am J Ophthalmol 2006;141:472-7.  Back to cited text no. 5


  [Figure 1], [Figure 2]


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