Clinical and molecular spectrum along with genotype-phenotype correlation of 25 patients diagnosed with 3 M syndrome: a study from Turkey.

Unlabelled: 3 M syndrome is a well-known autosomal recessive skeletal genetic disorder caused by biallelic pathogenic variants in the CUL7, OBSL1, and CCDC8 genes. Affected individuals exhibit profound pre- and postnatal growth retardation, distinctive facial features with normal intelligence. This study aims to provide insight into the comprehensive evaluation of clinical, laboratory, and radiological findings, expand the mutational spectrum of the disease, and establish a genotype-phenotype correlation in the present cases.

From Desbuquois Dysplasia to Multiple Epiphyseal Dysplasia: The Clinical Impact of a CANT1 Variant Across Five Unrelated Families.

Multiple epiphyseal dysplasia (MED) is a heterogeneous group of chondrodysplasia characterized by arthralgia, early onset osteoarthropathy, and the radiographic findings of small, flat, and irregular-shaped epiphyses. Some patients with MED have mild short stature as well. MED is genetically heterogeneous caused by pathogenic variants in COMP, MATN3, COL9A1, COL9A2, COL9A3, and SLC26A2.

Many Faces of Diencephalic-Mesencephalic Junction Dysplasia Syndrome with and Variants.

Introduction: Diencephalic-mesencephalic junction dysplasia syndrome is a rare neurogenetic disorder reported to be caused by variants in several genes. Phenotypic presentation is characterized by clinical findings including developmental delay, hypotonia, spasticity, and dyskinetic movements in combination with distinctive imaging features on brain magnetic resonance imaging (MRI).

Methods: Whole exome sequencing was conducted to unveil the molecular etiology of patients presenting with neurological manifestations from two unrelated families.

Review of patients with achondroplasia: a single-center's experience with follow-up and associated morbidities.

Achondroplasia (ACH; MIM #100,800), caused by a heterozygous gain of function pathogenic variant in the fibroblast growth factor receptor 3 gene (FGFR3; MIM*134,934), is the most prevalent and most readily identifiable cause of disproportionate short stature that is compatible with life. In addition, individuals with achondroplasia face significant medical, functional, and psychosocial challenges throughout their lives. This study assessed associated morbidities in patients with achondroplasia at a single center in Turkey.

Further defining the molecular spectrum and long-term follow-up of 17 patients with Dyggve-Melchior-Clausen and Smith-McCort dysplasia type 2.

Dyggve-Melchior-Clausen dysplasia (DMC) and Smith-McCort dysplasia (SMC types 1 and 2) are rare spondylo-epi-metaphyseal dysplasias with identical radiological and clinical findings. DMC and SMC type 1 are allelic disorders caused by homozygous or compound heterozygous variants in DYM, while biallelic causative variants in RAB33B lead to SMC type 2. The terminology "skeletal golgipathies" has been recently used to describe these conditions, highlighting the pivotal role of these two genes in the organization and intracellular trafficking of the Golgi apparatus.

Early diagnostic clues of mucolipidosis type II: Significance of radiological findings.

Mucolipidosis type-II (ML-II) is an ultra-rare disorder caused by deficiency of N-acetylglucosaminyl-1-phosphotransferase enzyme due to biallelic pathogenic variants in GNPTAB gene. There are a few known about the natural history of ML-II. In this study, we presented the natural course of 24 patients diagnosed with ML-II.

-Associated Immunoskeletal Dysplasia with Neurodevelopmental Abnormalities: A Lethal Phenotype.

Immunoskeletal dysplasia with neurodevelopmental abnormalities (ISDNA) caused by biallelic mutations is a very rare syndrome with only 16 cases reported in the literature. Skeletal dysplasia, neurodevelopmental delay, immunodeficiency, liver, and kidney cysts are the most common findings of this syndrome. Here, we report on a patient who exhibited a lethal phenotype with clinical characteristics of this syndrome and had a homozygous pathogenic mutation in gene.

Clinical Evaluation of Pediatric Patients with Hereditary Angioedema.

Hereditary angioedema is a rare, potentially life-threatening disease. There is a lack of data describing the clinical course of hereditary angioedema (HAE) in children. We aimed to evaluate the clinical characteristics of pediatric patients with hereditary angioedema: The age of disease onset, age at diagnosis, the frequency of angioedema attacks, the total number of attacks before diagnosis, the regions where angioedema attacks were observed, accompanying abdominal pain, and serum levels of C4 and C1 esterase inhibitor were obtained and recorded.

Spondylo-meta-epiphyseal dysplasia (SMED), short limb-hand abnormal calcification type: Further expanding the mutational spectrum and dental findings of three new patients.

Genetic skeletal disorders are clinically and genetically heterogeneous group of disorders that affect the normal development, growth, and maintenance of the human skeleton. Spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type (SMED-SL/AC; MIM# 271665) is a rare autosomal recessive genetic skeletal disorder characterized by distinctive facial features, disproportionate short stature, vertebral, metaphyseal, and epiphyseal abnormalities. This unique phenotype is caused by biallelic loss-of-function variants in Discoidin domain receptor 2 gene (DDR2, MIM# 191311).

A Rare Autoinflammatory Disorder in a Pediatric Patient with Favorable Response to Etanercept: Sideroblastic Anemia with B Cell Immunodeficiency, Periodic Fevers, and Developmental Delay Syndrome.

Sideroblastic anemia with B cell immunodeficiency, periodic fevers, and developmental delay (SIFD) syndrome is caused by biallelic TRNT1 mutations. TRNT1 gene encodes a CCA-adding tRNA nucleotidyl transferase enzyme. Mutant TRNT1 results in immunodeficiency and anemia in various degrees, accompanied by several organ involvement.

Investigation of Genetic Causes in a Developmental Disorder: Oculoauriculovertebral Spectrum.

Objective: Oculoauriculovertebral spectrum (OAVS) is a genetically and clinically heterogeneous disorder that occurs due to a developmental field defect of the first and second pharyngeal arches. Even though recent whole exome sequencing studies (WES) have led to identification of several genes associated with this spectrum in a subset of individuals, complete pathogenesis of OAVS remains unsolved. In this study, molecular genetic etiology of OAVS was systematically investigated.

Two Siblings with Kaufman Oculocerebrofacial Syndrome Resembling Oculoauriculovertebral Spectrum.

Kaufman oculocerebrofacial syndrome is a rare autosomal recessive disorder which represents a phenotype mainly involving craniofacial and neurodevelopmental manifestations due to gene mutations. The vast majority of the affected individuals exhibit microcephaly, eye abnormalities, and typical facial gestalt including blepharophimosis, ptosis, telecanthus, upslanting palpebral fissures, dysplastic ears, and micrognathia. We encountered 2 siblings in whom severe psychomotor delay, distinctive facial features, hearing loss, and respiratory distress were observed.

Three new cases of Crisponi /cold induced sweating syndrome (CS/CISS1) in Turkish families.

Crisponi syndrome/Cold Induced Sweating Syndrome 1 (CS/CISS1) is a rare, autosomal recessive, multisystemic disease. Hyperthermia attacks, abnormal contractions in the muscles of the face and oropharynx, respiratory distress, camptodactyly, and swallowing difficulty are the main features of the condition in the neonatal period. Patients experience cold-induced sweating attacks and progressive kyphoscoliosis in childhood and adolescence.

Natural history of TRPV4-Related disorders: From skeletal dysplasia to neuromuscular phenotype.

TRPV4-related disorders constitute a broad spectrum of clinical phenotypes including several genetic skeletal and neuromuscular disorders, in which clinical variability and somewhat overlapping features are present. These disorders have previously been considered to be clinically distinct phenotypes before their molecular basis was discovered. However, with the identification of TRPV4 variants in the etiology, they are referred as TRPV4-related disorders (TRPV4-pathies), and are now mainly grouped into skeletal dysplasias and neuromuscular disorders.

Further defining the clinical and molecular spectrum of acromesomelic dysplasia type maroteaux: a Turkish tertiary center experience.

Acromesomelic dysplasia type Maroteaux (AMDM, OMIM #602875) is an autosomal recessive disorder characterized by severe short stature, shortened middle and distal segments of the limbs, redundant skin of fingers, radial head subluxation or dislocation, large great toes and cranium, and normal intelligence. Only the skeletal system appears to be consistently affected. AMDM is caused by biallelic loss-of-function variants in the natriuretic peptide receptor B (NPRB or NPR2, OMIM #108961) which is involved in endochondral ossification and longitudinal growth of limbs and vertebrae.

Further Phenotypic Delineation of Partial Trisomy 17q and Partial Monosomy 20q due to Rare t(17;20).

Copy number variations in subtelomeric regions of chromosomes 17 and 20 are associated with intellectual disability and various systemic manifestations. Microarray analysis allows identification of submicroscopic chromosomal abnormalities and is applicable to elucidate the etiology of cognitive impairment in approximately one-fifth of the cases. In the present study, we report on 3 male children from 2 sisters, who suffered from intellectual disability, facial dysmorphism, and epilepsy.

Peters Plus syndrome: a recognizable clinical entity.

Peters plus syndrome is a rare genetic condition wherein multiple systemic involvement with distinctive facial features are manifested, whilst the hallmark is Peters anomaly, occuring from anterior segment dysgenesis. Homozygous variants in the B3GLCT gene were identified to underlie this disorder. We here report on a onemonth- old female patient with typical features characteristic of Peters plus syndrome in whom a homozygous pathogenic mutation in the B3GLCT gene was detected.

Ophthalmo-acromelic syndrome in an infant.

Ophthalmo-acromelic syndrome is a rare autosomal recessive disorder characterized by ocular and skeletal abnormalities. Ocular findings present as a wide spectrum, ranging from mild microphthalmia to true anophthalmia. Short 5th finger, synostosis of 4th and 5th metacarpals, and oligodactyly in feet are frequent limb malformations.

Hyperphosphatasia with mental retardation syndrome type 4 In two siblings-expanding the phenotypic and mutational spectrum.

Hyperphosphatasia with mental retardation syndrome (HPMRS) (OMIM # 239300), is an autosomal recessive disease with phenotypic variability, ranging from mild nonsyndromic intellectual disability to syndromic form with severe intellectual disability, seizures, elevated alkaline phosphatase, brachytelephalangy and facial dysmorphism, Six subgroups of HPMRS were defined in which pathogenic mutations affect genes involved in either synthesis or remodeling of the anchor proteins. Among these, PGAP3 mutations are associated with HPMRS type 4. We report two siblings with a novel homozygous variant in PGAP3 expanding both the phenotypic findings and the mutational spectrum of HPMRS type 4.

Further delineation of spondyloepimetaphyseal dysplasia Faden-Alkuraya type: A RSPRY1-associated spondylo-epi-metaphyseal dysplasia with cono-brachydactyly and craniosynostosis.

Our understanding of the molecular basis of the genetic disorders of the skeleton has steadily increased, as the application of high-throughput sequencing technology has expanded. One of the newcomers is Spondyloepimetaphyseal dysplasia Faden-Alkuraya type. In this study, we aimed to further delineate the clinical, radiographic, and molecular findings of this entity in five affected individuals from two unrelated families.

Further expansion of the mutational spectrum of spondylo-meta-epiphyseal dysplasia with abnormal calcification.

Spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type, is a rare autosomal recessive disorder of the skeleton characterized by disproportionate short stature with narrow chest and dysmorphic facial features. The skeletal manifestations include platyspondyly, short flared ribs, short tubular bones with abnormal metaphyses and epiphyses, severe brachydactyly, and premature stippled calcifications in the cartilage. The abnormal calcifications are so distinctive as to point to the definitive diagnosis.