Directly Transmitted 12.3-Mb Deletion with a Consistent Phenotype in the Variable 11q21q22.3 Region

2020 ◽  
Vol 160 (4) ◽  
pp. 185-192
Author(s):  
Beth Kirk ◽  
Mira Kharbanda ◽  
Mark S. Bateman ◽  
David Hunt ◽  
Emma-Jane Taylor ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Dosage Compensation ◽  
Learning Difficulties ◽  
Failure To Thrive ◽  
Interstitial Deletion ◽  
Speech Delay ◽  
Normal Range ◽  
Feeding Difficulties ◽  
Mother And Daughter ◽  
Normal Cognition

A phenotype is emerging for the proximal pair of G-dark bands in 11q (11q14.1 and q14.3) but not yet for the distal pair (11q22.1 and q22.3). A mother and daughter with the same directly transmitted 12.3-Mb interstitial deletion of 11q21q22.3 (GRCh37: 93,551,765-105,817,723) both had initial feeding difficulties and failure to thrive, speech delay, learning difficulties, and mild dysmorphism. Among 17 patients with overlapping deletions, developmental or speech delay, dysmorphism, hypotonia, intellectual disability or learning difficulties, short stature, and coloboma were each found in 2 or more. These results may provide the basis for a consistent phenotype for this region. Among the 53 deleted and additional breakpoint genes, CNTN5, YAP1, and GRI4 were the most likely candidates. Non-penetrance of haploinsufficient genes and dosage compensation among related genes may account for the normal cognition in the mother and variable phenotypes that can extend into the normal range.

Delineating the Clinical Spectrum Associated With Xq25q26.2 Duplications: Report of 2 Families and Review of the Literature

2018 ◽  
Vol 34 (2) ◽  
pp. 86-93 ◽  
Author(s):  
John C. Herriges ◽  
Ellen M. Arch ◽  
Pamela A. Burgio ◽  
Erin E. Baldwin ◽  
Danielle LaGrave ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Learning Difficulties ◽  
Growth Failure ◽  
Speech Delay ◽  
Review Of The Literature ◽  
Phenotype Correlation ◽  
Additional Insight ◽  
Dysmorphic Features ◽  
Phenotypic Spectrum ◽  
Insight Into

To date, 13 patients with interstitial microduplications involving Xq25q26.2 have been reported. Here, we report 6 additional patients from 2 families with duplications involving Xq25q26.2. Family I carries a 5.3-Mb duplication involving 26 genes. This duplication was identified in 3 patients and was associated with microcephaly, growth failure, developmental delay, and dysmorphic features. Family II carries an overlapping 791-kb duplication that involves 3 genes. This duplication was identified in 3 patients and was associated with learning disability and speech delay. The size and gene content of published overlapping Xq25q26.2 duplications vary, making it difficult to define a critical region or establish a genotype-phenotype correlation. However, patients with overlapping duplications have been found to share common clinical features including microcephaly, growth failure, intellectual disability, learning difficulties, and dysmorphic features. The 2 families presented here provide additional insight into the phenotypic spectrum and clinical significance of duplications in this region.

scholarly journals Comprehensive study of 28 individuals with SIN3A-related disorder underscoring the associated mild cognitive and distinctive facial phenotype

2021 ◽  
Author(s):  
Meena Balasubramanian ◽  
Alexander J. M. Dingemans ◽  
Shadi Albaba ◽  
Ruth Richardson ◽  
Thabo M. Yates ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Protein Function ◽  
Autism Spectrum ◽  
Loss Of Function ◽  
Mild Intellectual Disability ◽  
Related Disorder ◽  
Feeding Difficulties ◽  
Facial Phenotype ◽  
Novel Variants ◽  
Common Behaviour

AbstractWitteveen-Kolk syndrome (OMIM 613406) is a recently defined neurodevelopmental syndrome caused by heterozygous loss-of-function variants in SIN3A. We define the clinical and neurodevelopmental phenotypes related to SIN3A-haploinsufficiency in 28 unreported patients. Patients with SIN3A variants adversely affecting protein function have mild intellectual disability, growth and feeding difficulties. Involvement of a multidisciplinary team including a geneticist, paediatrician and neurologist should be considered in managing these patients. Patients described here were identified through a combination of clinical evaluation and gene matching strategies (GeneMatcher and Decipher). All patients consented to participate in this study. Mean age of this cohort was 8.2 years (17 males, 11 females). Out of 16 patients ≥ 8 years old assessed, eight (50%) had mild intellectual disability (ID), four had moderate ID (22%), and one had severe ID (6%). Four (25%) did not have any cognitive impairment. Other neurological symptoms such as seizures (4/28) and hypotonia (12/28) were common. Behaviour problems were reported in a minority. In patients ≥2 years, three were diagnosed with Autism Spectrum Disorder (ASD) and four with Attention Deficit Hyperactivity Disorder (ADHD). We report 27 novel variants and one previously reported variant. 24 were truncating variants; three were missense variants and one large in-frame gain including exons 10–12.

scholarly journals Successful Management of Feeding Difficulties in Patient with Severe Bilateral Cleft Lip and Palate

2014 ◽  
Vol 4 (2) ◽  
pp. 124-126
Author(s):  
Dimple Padawe ◽  
Vilas Takate ◽  
Tanay Gunjikar
Keyword(s):  
Cleft Lip ◽  
Developmental Disorder ◽  
Cleft Lip And Palate ◽  
Failure To Thrive ◽  
Later Life ◽  
Successful Management ◽  
Feeding Difficulties ◽  
Psychological Maladjustment ◽  
Bilateral Cleft Lip ◽  
Feeding Plate

ABSTRACT Cleft lip and palate is one of the most common developmental disorder found in humans. A child born with cleft lip and palate has plethora of complex problems, such as feeding difficulties, middle ear diseases, dentofacial abnormalities, slow weight gain, and even failure to thrive. Feeding difficulties are the main cause of distress for both the child and mother, and may also lead to psychological maladjustment of child in later life. Various methods have been described to overcome feeding difficulties faced child and mother. This case report describes a case of severe bilateral cleft lip and palate (Veau's class IV cleft) successfully managed by fabrication of simple feeding plate and counseling of mother. How to cite this article Padawe D, Takate V, Gunjikar T. Successful Management of Feeding Difficulties in Patient with Severe Bilateral Cleft Lip and Palate. J Contemp Dent 2014; 4(2):124-126.

scholarly journals MED13L-related intellectual disability due to paternal germinal mosaicism

2021 ◽  
pp. mcs.a006124
Author(s):  
Beata Bessenyei ◽  
Istvan Balogh ◽  
Attila Mokanszki ◽  
Aniko Ujfalusi ◽  
Rolph Pfundt ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
De Novo ◽  
Mediator Complex ◽  
Facial Dysmorphism ◽  
Facial Features ◽  
Speech Delay ◽  
Motor Delay ◽  
First Case ◽  
Intragenic Deletion ◽  
Germinal Mosaicism

The MED13L-related intellectual disability or MRFACD syndrome (Mental retardation and distinctive facial features with or without cardiac defects; MIM # 616789) is one of the most common form of syndromic intellectual disability with about a hundred cases reported so far. Affected individuals share overlapping features comprising intellectual disability, hypotonia, motor delay, remarkable speech delay, and a recognizable facial gestalt. De novo disruption of the MED13L gene by deletions, duplications or sequence variants has been identified deleterious. Siblings affected by intragenic deletion transmitted from a mosaic parent have been reported once in the literature. We now present the first case of paternal germinal mosaicism for a missense MED13L variant causing MRFACD syndrome in one of the father's children and be the likely cause of intellectual disability and facial dysmorphism in the other. As part of the Mediator complex, the MED proteins have an essential role in regulating transcription. 32 subunits of the Mediator complex genes have been linked to congenital malformations that are now acknowledged as transcriptomopathies. The MRFACD syndrome has been suggested to represent a recognizable phenotype.

Aryepiglottoplasty for laryngomalacia: 100 consecutive cases

2001 ◽  
Vol 115 (1) ◽  
pp. 35-38 ◽  
Author(s):  
S. C. Toynton ◽  
M. W. Saunders ◽  
C. M. Bailey
Keyword(s):  
Complication Rate ◽  
Neurological Disease ◽  
Failure To Thrive ◽  
Indications For Surgery ◽  
Airway Compromise ◽  
Feeding Problems ◽  
Street Hospital ◽  
Feeding Difficulties ◽  
Great Ormond Street Hospital ◽  
Feeding Difficulty

A retrospective review of the notes of 100 consecutive patients who had undergone aryepiglottoplasty for laryngomalacia, at Great Ormond Street Hospital for Children, was undertaken. Fifty-six were male, 44 female and 47 were under three months of age. Indications for surgery were oxygen desaturation below 92 per cent and feeding difficulties causing failure to thrive. Forty-seven patients had other pathology contributing to their airway compromise or feeding problems. Improvement in stridor after one month was achieved in 86/91 (94.5 per cent) being abolished completely in 50/91 (55 per cent). Of the 25 per cent of patients whose symptoms took more than one week to resolve, 16/22 (63.6 per cent) were later found to have a serious neurological condition. Feeding was improved in 42 of 58 patients (72.4 per cent) who had a pre-operative feeding difficulty. The complication rate was low, with only five out of 86 (10 per cent) experiencing initial worsening of the airway and six per cent having aspiration of early feeds before improvement occurred.Endoscopic aryepiglottoplasty remains the operation of choice for patients with severe laryngomalacia, however, in the presence of neurological disease surgery is less likely to be successful.

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