Disorders of DNA Maintenance, Transcription, and Translation



Disorders of DNA Maintenance, Transcription, and Translation





May be caused by abnormality in: (1) DNA repair following exposure to mutagens (nucleotide excision repair); (2) DNA duplication and transcription, (3) RNA splicing and translation; (4) cell cycle regulation.



  • Characteristic clinical features: neurodegeneration, impaired growth, premature aging, propensity to develop malignancies.

Specific conditions listed in Table 87.1.











Table 87.1 Clinical Features of Selected Disorders of DNA Synthesis, Maintenance, Transcription and Translation






























































Disorder Inheritance Specific features
DNA Maintenance and Transcription
Cockayne syndrome, Type 1 AR Mental retardation, accelerated aging, marked growth retardation, pigmentary retinopathy, optic atrophy, deafness, marble epiphyses, photosensitivity, calcification of basal ganglia, cerebellum.
Cerebro-oculofacioskeletal (COFS) syndrome AR Microcephaly, microphthalmia, cataracts, dysmorphism, failure to thrive, recurrent pneumonias, axial hypotonia, limb hypertonia, hyperreflexia, progressive contractures. Calcification in periventricular frontal white matter, basal ganglia.
Progeria AR Short stature, failure to thrive; accelerated aging, with loss of scalp hair and subcutaneous fat, joint stiffness, strokes, myocardial infarcts (due to early atherosclerosis), premature death. Cognition spared.
Xeroderma pigmentosum
(including de Sanctis-Cacchione syndrome)
AR Mental retardation, short stature, facial freckles, spasticity, hypogonadism, olivopontocerebellar atrophy.
Trichothiodystrophy (TTD 1) AR Mental retardation, hair shaft abnormalities, ichthyosis, immature sexual development, short stature, facial dysmorphism
Rett syndrome X-linked Classic phenotype restricted to females. Normal development for first six months, followed by acquired microcephaly, loss of hand skills and replacement by stereotypies, regression of skills, seizures, spasticity, scoliosis
Spinal muscular atrophy 1, 2, 3 AR Loss of anterior horn cells; limb weakness, loss of tendon jerks; visible fasciculation may be limited to tongue in infantile type 1.
DNA Translation and Post-translational Modification
CACH, Cree leukoencephalopathy, ovarioleukodystrophy AR Slowly progressive ataxia with diffuse loss of white matter. Episodes of coma with fever, minor trauma
Congenital disorder of glycosylation 1a (CDG 1a) AR Mental retardation, short stature, progressive ataxia, peripheral neuropathy, stroke-like episodes, seizures, immune dysfunction, intermittent hepatic failure, coagulopathies
Cell Cycle Regulation
Angelman syndrome Multiple mechanisms (see Ch 81) Psychomotor retardation, ataxia, hypotonia, epilepsy, absence of speech, large mandible, tongue thrusting. Optic atrophy, albinism in some.
Ataxia telangiectasia AR Progressive ataxia, choreoathetosis, anterior horn cell loss, immune deficiency, scleral telangiectasia.
Seckel syndrome 1 AR Short stature, dysmorphism (congenital microcephaly, mental retardation. No immune deficiency or cancers.
CACH, childhood ataxia with CNS hypomyelinization (formerly vanishing white matter disease).

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Jul 27, 2016 | Posted by in NEUROLOGY | Comments Off on Disorders of DNA Maintenance, Transcription, and Translation
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