A novel variant in the dystonin gene causing hereditary sensory autonomic neuropathy type <scp>VI</scp> in a male infant: Case report and literature review

Sakaria, Rishika P.; Fonville, Megan Parker; Peravali, Silpa; Zaveri, Parul G.; Mroczkowski, Henry Joel; Caron, Elena; Weems, Mark F.

doi:10.1002/ajmg.a.62609

Cited by 6 publications

(7 citation statements)

References 8 publications

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“…Biallelic variants in the neuronal isoforms cause HSAN6 (MIM: 614653) which has been reported in several unrelated families with highly variable phenotypes (Table 1). 6–20 HSAN6 was initially described in a family of four affected individuals who presented with severe dysautonomic symptoms, distal contractures, severe psychomotor retardation, and early death 8 . The motor phenotype of the affected fetus reported here is similar to the affected individuals reported by Edvardson et al More recently, HSAN6 was reported as associated with congenital contractures 9,10 .…”

Section: Discussionsupporting

confidence: 79%

“…HSAN6 was initially described in a family of four affected individuals who presented with severe dysautonomic symptoms, distal contractures, severe psychomotor retardation, and early death 8. The motor phenotype of the affected fetus reported here is similar to the affected individuals reported by Edvardson et al More recently, HSAN6 was reported as associated with congenital contractures 9,10. The positions of DST variants in the cases associated with congenital contractures are not restricted to a specific domain of the DST protein (tion.…”

supporting

confidence: 75%

“…) [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. HSAN6 was initially described in a family of four affected individuals who presented with severe dysautonomic symptoms, distal contractures, severe psychomotor retardation, and early death 8.…”

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confidence: 99%

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DST variants are responsible for neurogenic arthrogryposis multiplex congenita enlarging the spectrum of type VI hereditary sensory autonomic neuropathy

et al. 2023

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Arthrogryposis multiplex congenita (AMC) is a developmental condition characterized by multiple joint contractures resulting from reduced or absent fetal movements. Through whole‐exome sequencing combined with arrayCGH from DNA of a fetus presenting with early onset AMC, we identified biallelic loss of function variants in Dystonin (DST): a stop gain variant (NM_001144769.5:c.12208G > T:p.(Glu4070Ter)) on the neuronal isoform and a 175 kb microdeletion including exons 25–96 of this isoform on the other allele [NC_000006.11:g.(56212278_56323554)_(56499398_56507586)del]. Transmission electron microscopy of the sciatic nerve revealed abnormal morphology of the peripheral nerve with severe hypomyelination associated with dramatic reduction of fiber density which highlights the critical role of DST in peripheral nerve axonogenesis during development in human. Variants in the neuronal isoforms of DST cause hereditary sensory and autonomic neuropathy which has been reported in several unrelated families with highly variable age of onset from fetal to adult onset. Our data enlarge the disease mechanisms of neurogenic AMC.

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Section: Discussionsupporting

confidence: 79%

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confidence: 75%

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DST variants are responsible for neurogenic arthrogryposis multiplex congenita enlarging the spectrum of type VI hereditary sensory autonomic neuropathy

et al. 2023

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“…79 DST-related HSAN6 is rare but has a severe presentation early in life with neonatal hypotonia, respiratory failure, areflexia, and dysautonomia. 80 HEREDITARY NEURALGIC AMYOTROPHY Hereditary neuralgic amyotrophy, also known as hereditary brachial plexus neuropathy or hereditary brachial neuritis, is an autosomal dominant disorder that typically presents with a recurrent painful brachial plexus neuropathy. Individual episodes are clinically and electrophysiologically indistinguishable from the common idiopathic neuralgic amyotrophy or Parsonage-Turner syndrome.…”

Section: Key Pointsmentioning

confidence: 99%

“…HSAN4 is also uniquely associated with variable degrees of intellectual disability and anhidrosis, which can be complicated by life-threatening hyperthermia 79 . DST -related HSAN6 is rare but has a severe presentation early in life with neonatal hypotonia, respiratory failure, areflexia, and dysautonomia 80 …”

Section: Hereditary Sensory and Autonomic Neuropathymentioning

confidence: 99%

Hereditary Neuropathies

Hayes,

Sadjadi

2023

CONTINUUM: Lifelong Learning in Neurology

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OBJECTIVE This article provides an overview of hereditary neuropathies, describes the different hereditary neuropathy subtypes and the clinical approach to differentiating between them, and summarizes their clinical management. LATEST DEVELOPMENTS Increasingly available clinical genetic testing has broadened the clinical spectrum of hereditary neuropathy subtypes and demonstrated a significant overlap of phenotypes associated with a single gene. New subtypes such as SORD-related neuropathy and CANVAS (cerebellar ataxia, neuropathy, vestibular areflexia syndrome) have emerged. The optimization of clinical management has improved gait and motor function in the adult and pediatric populations. Novel therapeutic approaches are entering clinical trials. ESSENTIAL POINTS Hereditary neuropathies constitute a spectrum of peripheral nerve disorders with variable degrees of motor and sensory symptoms, patterns of involvement, and clinical courses.

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Hereditary sensory autonomic neuropathy type VI in the age of genetic testing

Peringassery Sateesh,

Chitamanni,

Akinsanmi

et al. 2024

Annals of the Child Neurology Society

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BackgroundHereditary sensory and autonomic neuropathy type VI (HSAN VI) is a rare recessive genetic disorder caused by mutations in the human dystonin (DST) gene. We report a novel homozygous alternate transcript mutation in the DST gene causing a severe neonatal form of HSAN VI.Patient DescriptionThis baby boy was born with severe hypotonia, respiratory distress, dysmorphic features, and bilateral club feet. Imaging, karyotyping, Prader–Willi assay, spinal muscular atrophy genetic panel and myotonic dystrophy genetic panel were all negative. A comprehensive neuropathy panel detected a homozygous pathogenic variant in the DST gene—alternate transcript NM_015546.4:c.1357G>A (p.Trp4525*). Nerve conduction studies revealed mixed axonal and demyelinating sensorimotor neuropathy, suggesting the possibility of motor involvement in severe forms of this rare condition. The infant ultimately developed sepsis and died from cardiorespiratory arrest. Neuropathological findings of focal and mild spinal nerve axonal degeneration were nonspecific.ConclusionCollective analysis of these patients would help to further characterize the spectrum of disease pathology and could provide insight into the neurophysiology and neuropathology of this rare condition.

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A novel variant in the dystonin gene causing hereditary sensory autonomic neuropathy type VI in a male infant: Case report and literature review

Cited by 6 publications

References 8 publications

DST variants are responsible for neurogenic arthrogryposis multiplex congenita enlarging the spectrum of type VI hereditary sensory autonomic neuropathy

DST variants are responsible for neurogenic arthrogryposis multiplex congenita enlarging the spectrum of type VI hereditary sensory autonomic neuropathy

Hereditary Neuropathies

Hereditary sensory autonomic neuropathy type VI in the age of genetic testing

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