Maternal uniparental isodisomy (iUPD) of chromosome 4 in a subject with mild intellectual disability and speech delay

Abstract Floating-Harbor syndrome (FHS) is a rare autosomal dominant syndrome characterized by short stature with delayed bone age, retarded speech development, intellectual disability and dysmorphic facial features. Recently, dominant mutations almost exclusively clustered in the final exon of the Snf2-related CREBBP activator protein (SRCAP) gene were identified to cause FHS. Here, we report a boy with short stature, speech delay, mild intellectual disability, dysmorphic features, and with genetically confirmed FHS. To the best of our knowledge, this is the first molecularly confirmed case with this syndrome reported in Romania. An intensive program of cognitive and speech stimulation, as well as yearly neurological, psychological, ophthalmological, otorhinolaryngological, pediatric and endocrinological monitoring for our patient were designed. We propose a checklist of clinical features suggestive of FHS, based on the main clinical features, in order to facilitate the diagnosis and clinical management of this rare condition.

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Segregation of a 4p16.3 duplication with a characteristic appearance, macrocephaly, speech delay and mild intellectual disability in a 3-generation family

American Journal of Medical Genetics Part A ◽

10.1002/ajmg.a.36099 ◽

2013 ◽

Vol 161 (9) ◽

pp. 2358-2362 ◽

Cited By ~ 6

Author(s):

Bitten Schönewolf-Greulich ◽

Kirstine Ravn ◽

Bente Hamborg-Petersen ◽

Karen Brøndum-Nielsen ◽

Zeynep Tümer

Keyword(s):

Intellectual Disability ◽

Speech Delay ◽

Mild Intellectual Disability ◽

Characteristic Appearance ◽

Generation Family ◽

4P16.3 Duplication

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

European Journal of Human Genetics ◽

10.1038/s41431-020-00769-7 ◽

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.

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