cleft palate and intellectual disability

BACKGROUND: Mandibulofacial dysostosis with microcephaly (MFDM, OMIM# 610536) is a rare monogenic disease that is caused by a mutation in the elongation factor Tu GTP binding domain containing 2 gene (EFTUD2, OMIM* 603892). It is characterized by mandibulofacial dysplasia, microcephaly, malformed ears, cleft palate, growth and intellectual disability. MFDM can be easily misdiagnosed due to its phenotypic overlap with other craniofacial dysostosis syndromes. The clinical presentation of MFDM is highly variable among patients...

OBJECTIVE: This study analyzed the systemic and oral abnormalities in individuals with Kabuki syndrome (KS) that might be investigated to enhance the early diagnosis and treatment by a multidisciplinary team, minimizing the consequences to the individual's health. STUDY DESIGN: Clinical examination was conducted on 15 individuals to investigate orodental alterations such as tooth abnormalities and cleft lip and/or palate, and the patient records were also reviewed to investigate systemic diseases such as cardiopathies, infectious and immunologic diseases, nephropathies, and delayed neuropsychomotor development...

BACKGROUND: Attention to the issue of intelligence and its promotion in children with cleft lip and cleft palate (CL and CP) is necessary to reduce their injuries in life. This study aimed to determine the intelligence quotient (IQ) and emotional intelligence (EQ) in children with CL and CP in comparison to healthy children. MATERIALS AND METHODS: In this descriptive study, 140 children, including 70 children with CL and CP, were selected from the Children treated in Craniofacial and Cleft Research Center, Spearman correlation, ANOVA and 70 healthy children were selected from the Pediatric Dentistry Department of Isfahan University, in the age range of 5-9 years...

OBJECTIVE: Auriculocondylar syndrome (ARCND) is a set of rare craniofacial malformations characterized by variable micrognathia, ear malformations, and mandibular condyle hypoplasia, and other accompanying features with phenotypic complexity. ARCND2 caused by pathogenic variants in the PLCB4 gene is a very rare disease with less than 50 patients reported and only 36 different variants of the PLCB4 gene recorded in HGMD. This study aims to enrich the patient resources, clinical data and mutational spectrum of ARCND2...

Neurodevelopmental disorders (NDDs) result from impaired development and functioning of the brain. Here, we identify loss-of-function (LoF) variation in ZFHX3 as a cause for syndromic intellectual disability (ID). ZFHX3 is a zinc-finger homeodomain transcription factor involved in various biological processes, including cell differentiation and tumorigenesis. We describe 42 individuals with protein-truncating variants (PTVs) or (partial) deletions of ZFHX3, exhibiting variable intellectual disability and autism spectrum disorder, recurrent facial features, relative short stature, brachydactyly, and, rarely, cleft palate...

Patau syndrome (trisomy 13) is a chromosomal abnormality with multiple malformations due to an additional copy of chromosome 13. This genetic condition has a systemic impact on the development of the human body, which can result in, but is not limited to, microphthalmia, microcephaly, low-set ears, cleft palate, cardiac abnormalities, and abdominal wall defects. It is associated with severe physical and intellectual disabilities and a limited lifespan. Here, we present a 29-year-old female with a high suspicion of the mosaic form of Patau syndrome...

Lenz-Majewski hyperostotic dwarfism (LMHD) is a rare condition characterized by intellectual disability, sclerosing bone dysplasia, dysmorphic facial features, brachydactyly, symphalangism and cutis laxa. Nineteen cases have been reported in the literature so far, eleven of them with PTDSS1 mutations. Although studies have had clinically similar findings, in some cases the authors have reported even rarer features such as hydrocephalus, facial paralysis, and cleft palate. We, hereby, report the case of the first patient with Lenz-Majewski syndrome (LMS) with molecular confirmation from Turkey...

INTRODUCTION: In contrast with the well-known and described deletion of the 22q11 chromosome region responsible for DiGeorge syndrome, 22q12 deletions are much rarer. Only a few dozen cases have been reported so far. This region contains genes responsible for cell cycle control, chromatin modification, transmembrane signaling, cell adhesion, and neural development, as well as several cancer predisposition genes. CASE PRESENTATION: We present a patient with cleft palate, sensorineural hearing loss, vestibular dysfunction, epilepsy, mild to moderate intellectual disability, divergent strabism, pes equinovarus, platyspondylia, and bilateral schwannoma...

OBJECTIVE: CDK13-related disorder (CDK13-RD) is a rare genetic condition first described in 2016 as involving congenital heart defects, dysmorphic facial features, and intellectual developmental disorder (CHDFIDD). Few studies have reported clinical presentations. There is very minimal information about cognitive and neuropsychological outcomes; however, developmental delays and intellectual disability are common. This study presents longitudinal neuropsychological outcomes of one adolescent with CKD13-RD...

Biallelic pathogenic variants in PGAP3 cause a rare glycosylphosphatidyl-inositol biogenesis disorder, PGAP3-CDG. This multisystem condition presents with a predominantly neurological phenotype, including developmental delay, intellectual disability, seizures, and hyperphosphatemia. Here, we summarized the phenotype of sixty-five individuals including six unreported individuals from our CDG natural history study with a confirmed PGAP3-CDG diagnosis. Common additional features found in this disorder included brain malformations, behavioral abnormalities, cleft palate, and characteristic facial features...

Chromosome 2p (chr2p) duplication, also known as trisomy 2p, is a rare chromosome abnormality associated with developmental delay, intellectual disability, behavioral problems, and distinctive facial features. Most of the reported cases involving trisomy 2p include additional copy number variants (CNVs) in other regions of the genome and are usually small in size. Little is known about the clinical outcomes of large duplications of chromosome 2p as the sole cytogenetic abnormality. In this study, 193 samples at the Greenwood Genetic Center (GGC) with CNVs involving chr2p were evaluated, out of which 86 had chromosome 2p duplications...

The recognition of syndromic forms of cleft palate is important for condition-specific management. Here, we report a patient with cleft palate, congenital heart disease, intellectual disability, and café-au-lait spots who had a deletion of chromosome 15q14. The identification of the precise breakpoints using a Nanopore-based long-read sequencer showed that the deletion spanned MEIS2 and SPRED1 loci. Cleft palate and café-au-lait spots can be ascribed to MEIS2 and SPRED1, respectively. Patients with cleft palate and café-au-lait spots should be encouraged to undergo a detailed genomic evaluation, including screening for a 15q14 deletion, to enable appropriate anticipatory medico-surgical management and genetic counseling...

BACKGROUND: Dental agenesis (DA) in the permanent dentition is one of the most common dental anomalies, with a prevalence up to 2-10%. Therefore, the aim of this retrospective study was to investigate the prevalence and therapeutic treatment of DA in healthy children (HC) compared to children with systemic disease or congenital malformation (SD/CM). METHODS: Out of 3407 patients treated at the Department of Paediatric Dentistry of the Justus Liebig University Giessen (Germany) between January 2015 and December 2020, a total of 1067 patients (594 female, 473 male) aged between 4...

INTRODUCTION: Chromosomal abnormalities are mostly found in 0.5-0.8% of live-born infants with developmental and morphological defects. Paracentric inversions are structural intrachromosomal rearrangements resulting in a risk of chromosomally unbalanced gametes in carriers. CASE PRESENTATION: Herein, we report a patient with dicentric rearrangement of chromosome 18 due to maternal paracentric inversion of chromosome 18. The patient was a girl, aged 3 years and 11 months...

Neurodevelopmental disorders (NDDs) result from impaired development and functioning of the brain. Here, we identify loss-of-function variation in ZFHX3 as a novel cause for syndromic intellectual disability (ID). ZFHX3, previously known as ATBF1, is a zinc-finger homeodomain transcription factor involved in multiple biological processes including cell differentiation and tumorigenesis. Through international collaboration, we collected clinical and morphometric data (Face2Gene) of 41 individuals with protein truncating variants (PTVs) or (partial) deletions of ZFHX3 ...

SATB2 -associated syndrome (SAS) is a rare condition, and it is characterized by severe developmental delay/intellectual disability, especially severe speech delay/or absence, craniofacial abnormalities, and behavioral problems. Most of the published reports are limited to children, with little information about the natural history of the disease and the possible novel signs and symptoms or behavioral changes in adulthood. We describe the management and follow-up of a 25-year-old male with SAS due to a de novo heterozygous nonsense variant SATB2 :c...

INTRODUCTION: Patients carrying interstitial deletions of the long arm of chromosome 9 show similar features. These phenotypes are often characterized by developmental delay, intellectual disability, short stature, and dysmorphism. Previously reported deletions differ in size and location spanning from 9q21 to 9q34 and were mostly detected by conventional cytogenetic techniques. METHODS: Based on clinical features suggesting primarily chromosomal diseases, aCGH analysis was indicated...

You-Hoover-Fong syndrome (YHFS) is an autosomal recessive condition caused by pathogenic variants in the TELO2 gene. Affected individuals were reported to have global developmental delay, intellectual disability, microcephaly, dysmorphic facial features, ocular involvement including cortical visual impairment, strabismus, cataract and rotatory nystagmus, movement disorder, hypertonia and spasticity, balance disturbance and ataxia, and abnormal sleep pattern. Other features reported include poor growth, cleft palate, cardiac malformations, epilepsy, scoliosis, and hearing loss...

This report presents a case of ring chromosome 7 syndrome with bilateral cleft lip and palate. A four-year-old boy presented with bilateral cleft lip and palate, microcephaly, clenched toes, cafe-au-lait spots, a history of epilepsy, and severe intellectual disability. Genetic karyotyping revealed 46 XY r(7) (p22q36). His cheiloplasty and delayed palatoplasty were successful. A review of 22 previous r(7) patients revealed that 22.7% had cleft lip and/or palate. This case demonstrates the importance of a multidisciplinary evaluation for cleft patients, particularly those with syndromic features and global developmental delay...

Many unbalanced large copy number variants reviewed in the paper are associated with syndromic orofacial clefts, including a 1.6 Mb deletion on chromosome 3q29. The current report presents a new family with this recurrent deletion identified via whole-exome sequencing and confirmed by array comparative genomic hybridization. The proband exhibited a more severe clinical phenotype than his affected mother, comprising right-sided cleft lip/alveolus and cleft palate, advanced dental caries, heart defect, hypospadias, psychomotor, and speech delay, and an intellectual disability...