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Indian J Dermatol
Indian J Dermatol
IJD
Indian J Dermatol
Indian Journal of Dermatology
0019-5154
1998-3611
Wolters Kluwer - Medknow India

IJD-69-366a
10.4103/ijd.ijd_1179_23
E–IJD®: Correspondence
Hereditary Sensory and Autonomic Neuropathy—Report of Two Cases in Siblings and Review of Literature
Gowda Shreya K
Garg Sonika
Behera Biswanath
Priyadharsan Bevan
Thakur Vishal
From the Department of Dermatology and Venereology, All India Institute of Medical Sciences, Bhubaneshwar, Odisha, India E-mail: drvishal87igmc@gmail.com
Jul-Aug 2024
19 8 2024
69 4 366366
12 2023
1 2024
Copyright: © 2024 Indian Journal of Dermatology
2024
https://creativecommons.org/licenses/by-nc-sa/4.0/ This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
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pmcDear Editor,

Hereditary sensory and autonomic neuropathy (HSAN) mainly affects the peripheral sensory and autonomic neurons. It clinically presents as distal sensory loss, acromutililation, foot deformity and osteonecrosis. Hereby we are reporting the case of two siblings presented to the dermatology outpatient department, a 12-year-old boy and a 16-year-old girl presented to the dermatology outpatient department with resorption of the bilateral toe and complaints of loss of pain sensation for 5–6 years. History of consanguineous marriage with similar complaints in parents. No history of recurrent diarrhoea, giddiness or loss of consciousness. No history of decreased sweating or tears. On examination, blood pressure and pulse were normal in both children. In the elder sister, cutaneous examination revealed bilateral great toe resorption, callosity and lichenified ulcers over the bilateral second toes [Figure 1]. Reduced sensation for cold, touch and pain was seen up to the bilateral ankle. Knee and ankle reflexes were diminished symmetrically. The bilateral common peroneal nerve and posterior tibial nerve were not thickened. Examination of younger brother showed resorption of the left great toe with callosity, and lichenified plaque over the right great toe and left second toe. Additionally, the bilateral dorsal of the hand showed callosities over proximal interphalangeal joints. Dystrophic and hanging nails were observed over bilateral fingers [Figure 2]. Sensory and motor examinations were similar to those of the previous case.

Figure 1 Clinical picture depicts resorption of left great toe, with lichenification and hypertrophy of right great toe and left second toe. Multiple hangnails, nail dystrophy, with areas of scarring over knuckles and dorsal of fingers

Figure 2 Clinical image shows resorption of bilateral great toes, with lichenification and hypertrophy of bilateral second toes. Multiple areas of scarring over the dorsal of the hands

The nerve conduction study demonstrated symmetrical sensory axonal polyneuropathy. A slit skin smear revealed no lepra bacilli. The starch iodine test showed a colour change to blue-black suggestive of intact sweating. The patient denied genetic analysis due to financial constrain. Diagnosis of HSAN was made on clinical evaluation and inheritance in the family, but subtyping was not done due to overlapping of symptoms among variants of HSAN.

The clinically and genetically diverse category of inherited peripheral neuropathies known as HSAN, largely affects the peripheral sensory and autonomic neurons. The diagnostic criteria of HSAN type 1[1]:

Main features

Prominent/predominant distal sensory loss

Repeated foot ulcerations/acromutilations

Osteonecrosis.

Additional criteria

Variable distal motor involvement

Foot deformity

Autonomic disturbances

Skin changes (hyperkeratosis, blisters, onychomycosis, etc.)

Autosomal dominant inheritance.

Patients typically show substantial distal sensory loss and, in some cases, a clear insensitivity to pain. The prominent distal sensory loss frequently causes chronic ulcerations in the hands and feet, and in rare cases, it can also cause osteomyelitis, which can be fatal and require the amputation of the toes, fingers or even more proximal parts of the extremities.[2] Some individuals have autonomic dysfunction, which can manifest as anhidrosis, fever, erratic blood pressure and gastrointestinal issues. Axonal nerve injury of the sensory neurons is frequently shown electrophysiologically, although further demyelination may also be present.[3]

Both autosomal dominant (AD) and autosomal recessive (AR) genetic mechanisms can be seen in HSAN. The AR types of HSAN typically present as congenital syndromes with striking sensory and autonomic abnormalities or as almost entirely autonomic disorders, whereas the AD types typically present in the second or third decade of life with marked sensory involvement, and minimal autonomic and variable motor involvement.[3] A classification of the hereditary sensory neuropathies into types HSAN I–V (Dyck 1983)[4] was made based on age at onset, inheritance pattern and additional features. The summary of clinical presentations and genes involved in various types of HSAN is summarised in Table 1.

Table 1 Summarizes the types of hereditary sensory autonomic neuropathy (HSAN)[456]

Type	Gene	Inheritance	Locus	Clinical features	Age of onset	
HSAN IA (most common)	SPTLC1	AD	9q22.2	Predominant loss of pain and temperature	Adult	
Preservation of vibration sense		
Lancinating pain		
Variable distal motor involvement		
HSAN IB	Unknown	AD	3p24-p22	Predominant sensory neuropathy (cough and gastroesophageal reflux) rarely foot ulceration	Adult	
HSAN IC	RAB7	AD	3q21	Prominent distal motor loss	Adult	
Sensory loss of all qualities		
Acro-mutilations		
HSAN II	WNK1/HSN2	AR	12p13.3	Predominant sensory loss	childhood	
Mutilation of hands and feet. Acropathy		
HSAN III	IKBKAP Riley Day dysautonomia	AR	9q31	Prominent autonomic dysfunction	Congenital	
Absent fungiform papillae		
Alacrimia		
Absent sweating		
HASN IV	NTRK 1 Congenital Insenstivity to pain	1q21	AR	Reduced pain sensation	Congenital	
Anhidrosis		
Episodic fever		
Mild Mental retardation		
Cornea lesions and joint deformities		
HSAN V	NGFB	1p13.1	AR	Painless fracture	Congenital	
Joint deformities		
Insensitivity to pain		
Normal intelligence		
HSAN with spastic paraplegia	CCT5	5p15	AR	Prominent sensory neuropathy	Early childhood	
Mutilating acropathy		
Spastic paraplegia		

Even though the clinical classification of these HSAN types is based on a small sample size of patients, it is still valid considering the recent molecular characterisation of the subtypes. The AD version of HSAN has varied motor involvement, making it challenging to distinguish it from Charcot-Marie-Tooth disease or hereditary motor and sensory neuropathy. We are presenting this case due to the rare occurrence of the disease.

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

Nil.

Conflicts of interest

There are no conflicts of interest.

Acknowledgment

We thank the patient for granting permission for clinical photography.
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1 Auer-Grumbach M Hereditary sensory neuropathy type I Orphanet J Rare Dis 2008 3 7 18348718
2 Elhennawy K Reda S Finke C Graul-Neumann L Jost-Brinkmann PG Bartzela T Oral manifestations, dental management, and a rare homozygous mutation of the PRDM12 gene in a boy with hereditary sensory and autonomic neuropathy type VIII: A case report and review of the literature J Med Case Rep 2017 11 233 28807049
3 Ashwin DP Chandan GD Jasleen HK Rajkumar GC Rudresh KB Prashanth R Hereditary sensory and autosomal peripheral neuropathy-type IV: Case series and review of literature Oral Maxillofac Surg 2015 19 117 23 25744033
4 Dyck PJ Mellinger JF Reagan TJ Horowitz SJ McDonald JW Litchy WJ Not ‘indifference to pain’ but varieties of hereditary sensory and autonomic neuropathy Brain 1983 106 373 90 6189547
5 Butler J Fleming P Webb D Congenital insensitivity to pain –review and report of a case with dental implications Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006 101 58 62 16360608
6 Kouvelas N Terzoglou C Congenital insensitivity to pain with anhidrosis: Case report Pediatr Dent 1989 11 47 51 2483264
