SCIENTIFIC LETTER Hereditary Sensory Polyneuropathy, Pain Insensitivity and Global Developmental Delay due to Novel Mutation in PRDM12 Gene Arushi Gahlot Saini 1 & Hansashree Padmanabh 1 & Jitendra Kumar Sahu 1 & Ingo Kurth 2 & Martin Voigt 2 & Pratibha Singhi 1 Received: 23 August 2016 /Accepted: 19 December 2016 # Dr. K C Chaudhuri Foundation 2017 To the Editor: A 2-y-old boy, born to consanguineous muslim parents, presented with global developmental delay and insen- sitivity to pain and temperature noticed since early infancy. He had infrequent spontaneous as well as reflexive blinking. He never cried after any fall, trauma or vaccination and did not show aversion to cold or hot water. He perceived touch, elicited normal sweating and tear overflow. There was no episodic flushing, bloating, gastrointestinal problems, hy- perhidrosis/anhidrosis, fever, seizures, extrapyramidal movements or focal motor deficits. Family history was not remarkable. Examination showed normal head-circum- ference, dolicocephalic head, frontal bossing, deep set eyes, mutilated lower lip and tongue due to excessive biting (Fig. 1), presence of fungiform papillae, rocker bot- tom feet, mild hypotonia, normal strength, absent muscle- stretch-reflexes, and absent response to deep touch, pain and temperature. Pupillary responses, sweating pattern and blood pressure records were normal. His developmental age was 10–11 mo. Rest of the examination in the child and parents was unremarkable. A clinical diagnosis of hereditary sensory and autonomic neuropathy (HSAN) was considered. Nerve conduction studies showed non-recordable sensory potentials and normal motor potentials in both upper and lower limbs. Magnetic-resonance-imaging of the brain was normal. Serum uric acid was 5.2 mg/dl (normal range: 4–8 mg/dl). Nerve and skin biopsies were refused by the parents. Next-generation sequencing of the pain-related genes revealed a novel homozygous splice-site mutation c.224-2A > G in the PRDM12 gene; both parents were heterozygous carriers. HSANs are clinically and genetically heterogeneous group of inherited neuropathies predominantly affecting peripheral sensory and autonomic neurons [1, 2]. PRDM12 gene is cur- rently recognized as the master regulator of sensory neuronal specification and plays a critical role in pain perception; its mutations commonly lead to congenital pain-insensitivity [3]. Our case highlights a novel PRDM12 mutation presenting as early-onset, autosomal-recessive sensory polyneuropathy, congenital insensitivity to pain, touch and temperature, global developmental delay and early loss of muscle stretch reflexes. However, the genotype-phenotype correlation of mutations in PRDM12 is still emerging and identification of addition- al cases may help elucidate its definitive disease course. We emphasize the role of genetic testing in differential diagno- sis of children presenting with pain-insensitivity and self- mutilation behavior. Fig. 1 Clinical photograph of the patient showing mutilated lower lip and tongue due to excessive biting and absence of pain perception * Pratibha Singhi doctorpratibhasinghi@gmail.com 1 Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India 2 Institute of Human Genetics, Jena University Hospital, 07743 Jena, Germany Indian J Pediatr DOI 10.1007/s12098-016-2284-y