Decreased level of consciousness in a toddler with overgrowth syndrome

Physicians caring for patients with rare diseases face unique challenges in managing symptoms, ordering diagnostic tests, and providing patients and families with anticipatory guidance. We describe the case of a toddler with overgrowth syndrome, and previously known ophthalmological and neurological findings, presenting with decreased level of consciousness (LOC) following a fall. We highlight the extensive workup undertaken in a patient with symptoms spanning multiple systems but lacking a unifying diagnosis. In this case, rapid whole exome sequencing identified a de novo CACNA1A gene mutation encoding a calcium channel subunit, located within chromosome region 19p13.13. We explore 19p13.13 Microdeletion Syndrome and compare our patient’s presentation to the cases described in the literature. Although our patient had several symptoms consistent with 19p13.13 Microdeletion Syndrome, others remain unexplained. This highlights the difficulty in determining a definitive diagnosis or treatment plan in the realm of rare diseases and emphasizes the need for further research into the disease process and development of novel therapies.

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Pain

10.1093/med/9780190466268.003.0012 ◽

2018 ◽

Author(s):

Marc Brodsky ◽

Ann E. Hansen

Keyword(s):

Quality Of Life ◽

Older People ◽

Emotional Experience ◽

Treatment Plan ◽

Disease Process ◽

Persistent Pain ◽

Negative Effects ◽

Multiple Systems ◽

Therapeutic Modalities

Persistent pain is an unpleasant sensory and emotional experience that continues for a prolonged period of time and that may or may not be associated with a recognizable disease process. Older people may suffer from conditions such as knee osteoarthritis, low back pain, neck pain and headache, neuropathic pain, fibromyalgia, and cancer-related pain. Pain may impact physical function, psychological function, and other aspects of quality of life. A thorough history and physical examination may optimally assess a person with a persistent pain complaint in the context of a multifactorial pathway from accumulated impairments in multiple systems. Older people may perceive that integrative medicine treatments based on lifestyle and lower-risk therapies may help them get relief from pain and improve quality of life. Follow-up evaluation of positive and negative effects of therapeutic modalities and medications may guide the treatment plan.

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Identification and molecular characterization of de novo translocation t(8;14)(q22.3;q13) associated with a vascular and tissue overgrowth syndrome

Cytogenetic and Genome Research ◽

10.1159/000059343 ◽

2001 ◽

Vol 95 (3-4) ◽

pp. 183-188 ◽

Cited By ~ 42

Author(s):

Q. Wang ◽

A.A. Timur ◽

P. Szafranski ◽

A. Sadgephour ◽

V. Jurecic ◽

...

Keyword(s):

Molecular Characterization ◽

De Novo ◽

Overgrowth Syndrome ◽

De Novo Translocation

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Identification of a patient with intellectual disability and de novo 3.7Mb deletion supports the existence of a novel microdeletion syndrome in 2p14–p15

Gene ◽

10.1016/j.gene.2012.12.027 ◽

2013 ◽

Vol 516 (1) ◽

pp. 158-161 ◽

Cited By ~ 9

Author(s):

Miroslava Hancarova ◽

Sarka Vejvalkova ◽

Marie Trkova ◽

Jana Drabova ◽

Alzbeta Dleskova ◽

...

Keyword(s):

Intellectual Disability ◽

De Novo ◽

Microdeletion Syndrome

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Multiple Dural Arteriovenous Fistulas

Interventional Neuroradiology ◽

10.1177/159101990200800210 ◽

2002 ◽

Vol 8 (2) ◽

pp. 183-191 ◽

Cited By ~ 4

Author(s):

A.J.P. Goddard ◽

M.S. Khangure

Keyword(s):

De Novo ◽

Disease Process ◽

Venous Drainage ◽

Transverse Sinus ◽

Dural Sinus ◽

External Carotid ◽

Unique Case ◽

Arteriovenous Fistulas ◽

Type Iv ◽

Dural Arteriovenous Fistulas

Dural arteriovenous fistulas are most probably acquired lesions. However, they have been rarely encountered de novo. We present a unique case of a 71-year-old woman who initially presented with right-sided dural arteriovenous fistula (DAVF), which spontaneously resolved after diagnostic arteriography. She later developed asymptomatic occlusion of the left transverse sinus. Five years after her initial presentation she developed left-sided pulse-synchronous tinnitus. MRA and catheter angiography showed a complex type IV DAVF between the left transverse sinus and multiple dural branches arising from both left and right external carotid arteries. The left transverse sinus was isolated from the torcula herophili, with stenosis of the sigmoid sinus. Extensive cortical venous drainage was demonstrated. Endovascular cure was effected by polyvinyl alcohol particle and absolute alcohol occlusion of the dominant dural supply, and transvenous coil occlusion of the left transverse sinus. The patient's symptoms resolved almost immediately. This unique case demonstrates that dural sinus occlusion and DAVFs may co-exist, but there may not be a causal relationship. It is likely that both DAVFs and sinus occlusion are manifestations of the same disease process characterised by a pro-thrombotic state and secondary angiogenesis. It is important to recognise that changes in symptomatology, even long after apparent disappearance of a lesion may indicate recurrence, and careful follow up is advocated.

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A Case With 4 de Novo Copy Number Variations With Clinical Features That Overlap 1q43q44 Microdeletion and 3q29 Microduplication Syndromes

Child Neurology Open ◽

10.1177/2329048x18798200 ◽

2018 ◽

Vol 5 ◽

pp. 2329048X1879820

Author(s):

Miriam Kessi ◽

Jing Peng ◽

Lifen Yang ◽

Haolin Duan ◽

Yulin Tang ◽

...

Keyword(s):

Intellectual Disability ◽

Corpus Callosum ◽

Copy Number ◽

De Novo ◽

Copy Number Variations ◽

Language Delay ◽

Global Developmental Delay ◽

Recurrent Infections ◽

Dental Anomalies ◽

Microdeletion Syndrome

1q43q44 microdeletion syndrome is characterized by intellectual disability/global developmental delay, epilepsy, dysmorphic facies, stereotypic movement, language delay, recurrent infections, dental anomalies, and hand and foot anomalies. Microcephaly and corpus callosum dysplasia are present in some cases depending on gene content. 3q29 microduplication syndrome is characterized by intellectual disability, language delay, microcephaly, and dental anomalies. We report the first case with 4 de novo copy number variations with clinical features which overlap 1q43q44 microdeletion and 3q29 microduplication syndromes. Our case presented with global developmental delay, epilepsy, recurrent infections, stereotypic movements, speech delay, microcephaly, facial dysmorphism, bilateral clinodactyly, and small puffy feet with metatarsus varus; however, she had no corpus callosum dysplasia. Our case highlights the role of multiple copy number variations in the occurrence of a certain phenotype. Moreover, it supports the theory that the loss of HNRNPU gene function cannot explain the occurrence of microcephaly and abnormalities of the corpus callosum in 1q43q44 microdeletion syndrome.

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A New Case of 13q12.2q13.1 Microdeletion Syndrome Contributes to Phenotype Delineation

Case Reports in Genetics ◽

10.1155/2014/470830 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5

Author(s):

Giorgia Mandrile ◽

Eleonora Di Gregorio ◽

Alessandro Calcia ◽

Alessandro Brussino ◽

Enrico Grosso ◽

...

Keyword(s):

Clinical Features ◽

Critical Region ◽

Array Cgh ◽

De Novo ◽

Genetic Disorder ◽

Phenotypic Expression ◽

Microdeletion Syndrome ◽

Complex Rearrangement

A recently described genetic disorder has been associated with 13q12.3 microdeletion spanning three genes, namely,KATNAL1, LINC00426, andHMGB1. Here, we report a new case with similar clinical features that we have followed from birth to 5 years old. The child carried a complex rearrangement with a double translocation: 46,XX,t(7;13)(p15;q14),t(11;15)(q23;q22). Array-CGH identified ade novomicrodeletion at 13q12.2q13.1 spanning 3–3.4 Mb and overlapping 13q12.3 critical region. Clinical features resembling those reported in the literature confirm the existence of a distinct 13q12.3 microdeletion syndrome and provide further evidence that is useful to characterize its phenotypic expression during the 5 years of development.

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Terminal microdeletions of 13q34 chromosome region in patients with intellectual disability: Delineation of an emerging new microdeletion syndrome

Molecular Genetics and Metabolism ◽

10.1016/j.ymgme.2016.03.007 ◽

2016 ◽

Vol 118 (1) ◽

pp. 60-63 ◽

Cited By ~ 6

Author(s):

Eyal Reinstein ◽

Meytal Liberman ◽

Michal Feingold-Zadok ◽

Tamar Tenne ◽

John M. Graham

Keyword(s):

Intellectual Disability ◽

Chromosome Region ◽

Microdeletion Syndrome

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Critical illness

10.1093/med/9780199568741.003.0147 ◽

2018 ◽

Author(s):

Matt Wise ◽

Paul Frost

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Critical Illness ◽

Respiratory Rate ◽

Early Warning ◽

Urine Output ◽

Disease Process ◽

Medical Review ◽

Clinical Observations ◽

Level Of Consciousness

Critical illness can be considered to be any disease process which causes physiological instability that leads to disability or death within minutes or hours. Fortunately, physiological instability associated with critical illness is easily detected by perturbations of simple clinical observations such as blood pressure, heart rate, respiratory rate, oxygen saturations, level of consciousness, and urine output. Individual abnormalities in these observations are sensitive for the presence of critical illness but non-specific. Specificity for critical illness improves as the number of abnormal clinical observations increases. Over recent years, a greater appreciation of the importance of deviations in simple clinical observations as a method of detecting critical illness has led to the development of a number of ‘early warning’ or ‘track and trigger’ systems. These systems attribute a score according to the magnitude and number of abnormal observations that are present, and a high score prompts immediate medical review. Although intuitively sensible, the evidence that these systems are effective in ameliorating or preventing critical illness is currently lacking. This chapter looks at the approach to diagnosis of critical illness, including the pitfalls in diagnosis.

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A Private 16q24.2q24.3 Microduplication in a Boy with Intellectual Disability, Speech Delay and Mild Dysmorphic Features

Genes ◽

10.3390/genes11060707 ◽

2020 ◽

Vol 11 (6) ◽

pp. 707 ◽

Cited By ~ 1

Author(s):

Orazio Palumbo ◽

Pietro Palumbo ◽

Ester Di Muro ◽

Luigia Cinque ◽

Antonio Petracca ◽

...

Keyword(s):

Intellectual Disability ◽

De Novo ◽

Chromosome Region ◽

Snp Array ◽

Supporting Evidence ◽

Speech Delay ◽

Dysmorphic Features ◽

Phenotype Comparison ◽

Molecular Comparison ◽

Snp Array Analysis

No data on interstitial microduplications of the 16q24.2q24.3 chromosome region are available in the medical literature and remain extraordinarily rare in public databases. Here, we describe a boy with a de novo 16q24.2q24.3 microduplication at the Single Nucleotide Polymorphism (SNP)-array analysis spanning ~2.2 Mb and encompassing 38 genes. The patient showed mild-to-moderate intellectual disability, speech delay and mild dysmorphic features. In DECIPHER, we found six individuals carrying a “pure” overlapping microduplication. Although available data are very limited, genomic and phenotype comparison of our and previously annotated patients suggested a potential clinical relevance for 16q24.2q24.3 microduplication with a variable and not (yet) recognizable phenotype predominantly affecting cognition. Comparing the cytogenomic data of available individuals allowed us to delineate the smallest region of overlap involving 14 genes. Accordingly, we propose ANKRD11, CDH15, and CTU2 as candidate genes for explaining the related neurodevelopmental manifestations shared by these patients. To the best of our knowledge, this is the first time that a clinical and molecular comparison among patients with overlapping 16q24.2q24.3 microduplication has been done. This study broadens our knowledge of the phenotypic consequences of 16q24.2q24.3 microduplication, providing supporting evidence of an emerging syndrome.

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