Year 2024, Volume 7 - Issue 1

There are many difficulties in managing genetic illnesses in the Middle East because of its complex genetic makeup and particular environmental conditions. Middle Eastern populations are characterized by high levels of inbreeding, large family sizes, and high mother and paternal ages. In the Middle East, genetic abnormalities are prevalent and contribute significantly to both physical and mental disabilities. In general, there are deficiencies in public health initiatives aimed at preventing genetic and congenital illnesses, which are further limited by legal and cultural constraints.

Background: Many uncommon metabolic disorders have a high prevalence in Arab countries due to the high rate of consanguineous marriages. This study aimed to assess the prevalence of Gaucher disease (GD) in patients with splenomegaly and/or thrombocytopenia of unknown cause in Saudi Arabia. Methods: This screening study was conducted in 13 hematology and hematopathology centers in Saudi Arabia over 2 years. Patients with splenomegaly and/or thrombocytopenia of unknown cause for at least a year were included. Enzyme activity in eligible patients was assessed using a dried blood spot sample. Results: Out of 390 patients, 87.4% had thrombocytopenia. In comparison, 8.8% had a history of splenectomy, and nearly 67.7% had splenomegaly. Fatigue, bone crises, and abdominal pain were commonly reported among adult patients. Anemia was the most common symptom among pediatric patients, followed by splenomegaly and easy bruising or bleeding. One patient was found to have GD. She was a Saudi toddler with no family history of GD, acid sphingomyelinase deficiency, or other genetic abnormalities. The GD patient's neurological, cardiac, and skeletal examinations were normal. Conclusion: This screening study paves the way for GD screening in Saudi Arabia. It also emphasizes the importance of early diagnosis, proper care, and positive outcomes for GD.

Background: Kohlschutter–Tonz syndrome (KTS) is a rare genetically heterogeneous autosomal recessive syn drome initially described in 1974 and characterized by the triad of infantile-onset epilepsy, amelogenesis imperfecta, and developmental delay. KTS patients share a common genetic trait, namely a variant in the ROGDI gene, a gene of unknown function that maps to chromosome 16p13.3. Methods: Following appropriate ethical and logistical measures, we reviewed literature cases with the ROGDI variant and presented one novel case diagnosed using whole exome sequencing. Clinical, genetic, developmental, and radiological data were reviewed and compared accordingly. Results: There were 22 studies involving the ROGDI variant, including one additional novel case we reported. Thirteen patients were males, and ten were females. The current age range was 2–24 years. The majority of patients had their first seizure episode between 6 and 12 months. Birth parameters were within normal limits. The majority had unspecified forms of seizures, followed by generalized tonic-clonic and focal tonic-clonic seizures with secondary generalization. Patients with controlled seizures were likely on leveti racetam. Amelogenesis imperfecta and yellowish teeth were distinctive hallmarks. Behavioral problems were observed in one-third of the cases. Electroencephalogram (EEG) and magnetic resonance imaging (MRI) were abnormal in nearly one-third of the cases. Conclusion: Identifying and drawing conclusive evidence for patients with the ROGDI variant was challenging. Conflicting reports on the efficacy of different anti-seizure medications and the adequate treatment modalities were observed. Potential hallmarks continue to be established. Current evidence can be validated, and a delineation of clinical and molecular findings can be achieved with additional cases.

Background: Brachydactyly A1 (BDA1) is an autosomal dominant disorder. It manifests as shortness/absence of the middle phalanges in the hands and feet. It is caused by a variation in the Indian hedgehog (IHH) gene. The IHH gene plays an important role in the development of limbs. IHH is expressed in the pre-hypertrophic chondrocytes of cartilage elements, where it regulates the rate of hypertrophic differentiation. A lack of IHH prevents proliferating chondrocytes from initiating the hypertrophic differentiation process. This study aimed to identify IHH gene variants in BDA1 individuals. Methods: The present study used Sanger sequencing to analyze IHH variants in three exons and in silico tools for detailed variant analysis. Results: A total of 44 individuals were sequenced - 14 BDA1 individuals and 30 healthy controls. Sanger sequencing revealed a novel variant in the IHH gene in exon 1 and exon 2. A variant was found to segregate affected individuals in a family. Conclusion: The present study findings further expand the mutation spectrum of the IHH gene, and provide detailed mutant protein changes by in silico methods. The study also provides additional evidence that IHH plays an important role in limb development and short stature.

Background: Down syndrome is one of the most common chromosomal abnormalities occurring in approximately 1 in 700 live births. The majority of cases are attributed to the presence of an additional copy of chromosome 21, resulting in a total chromosome count of 47, as opposed to the typical 46. Distinctive facial characteristics commonly associated with this condition include but are not limited to, upslanting palpebral fissures, epicanthal folds, protruding tongue, and brachycephaly. Other clinical manifestations encompass hypotonia, intellectual disability, and congenital heart defects, among others. Case Presentation: In this article, we present the case of a premature neonate delivered at 32 weeks of gestation via emergency cesarean section due to absent diastolic flow. The patient's prenatal history was significant for intrauterine growth restriction. Following birth, the patient displayed very subtle dysmorphic features, notably upslanting palpebral fissures, without additional features suggestive of Down syndrome (DS). Chromosomal analysis revealed an isodicentric chromosome 21 (46, XX idic(21)(q22.3). Array comparative genomic hybridization revealed a concurrent duplication of the majority of chromosome 21 [21p11.2q22.3(7761419_41294939)] and a 4.5 Mb deletion of the long arm of chromosome 21, specifically 21q22.3(41295017_46677460). Conclusion: Our study highlights a unique etiology of Down syndrome that is associated with a milder pheno-type. However, its limitations include the rarity of the case, which restricts the availability of comparative data, and potential influencing factors like prematurity and low birth weight.

Background: Identifying the cause of recurrent pregnancy loss (RPL) helps in the direct management of future pregnancies. In 3%-4% of cases, a chromosomal structural rearrangement is identified in the couple. Pre-implantation genetic testing - structural rearrangements (PGT-SR) is an accepted practice for such couples opting for pregnancy through in-vitro fertilization. However, the result interpretation and clinical outcome for mosaic embryo transfer have limited predictions. Case Presentation: In this case study, we describe the genetic tests involved in establishing the cause of RPL followed by management through PGT and prenatal diagnosis. The couple was identified with a structural rearrangement and opted for PGT-SR (structural rearrangement) which revealed a mosaic embryo involving multiple chromosomes. The case study describes the implication of the transfer of mosaic embryos, followed up with prenatal tests with complex results, its interpretation, and genetic counseling. Conclusion: The case reiterates the benefit of thorough genetic evaluation for pregnancy management by using multiple genetic tests for couples with RPL. It aids in decision-making for complex genetic results in prenatal scenarios.

Background: Waardenburg syndrome is a rare genetic disorder with distinct characteristics. Since their discovery, some types of WS have been reported only once. Type 2F, the subject of this article, has only eleven reported cases worldwide. Case Presentation: In this article, we report a 15-year-old female patient with type 2F who exhibited bilateral sensorineural hearing loss. It is the first reported case of WS type 2F with albinism since birth, type 1 diabetes mellitus (DM), absent internal female reproductive organs, and short stature. Conclusion: In the current case, it might be classified as a new type of WS with this distinguished and unique presentation. Consanguineous marriages might reveal hidden diseased genes. This condition requires a multidisciplinary team management.

Background: Ring chromosome 8 is a rare cytogenetic condition, with limited clinical and genetic characterization. Case Presentation: We hereby report a case of a 4-month-old male child with craniofacial dysmorphism (microcephaly, aural dysplasia, anteverted nares, micrognathia, and visuo-ocular manifestations), global developmental delay, hypotonia, cryptorchidism, and other skeletal abnormalities. Investigations further facilitated the detection of semilobar holoprosencephaly, non-obstructive hypertrophic cardiomyopathy, and mal-ascended ectopic kidney. Result: GTG-Banding revealed a Karyotype 46 XY, r(8) in the proband, while a normal parental karyotype suggesting non-inheritance of ring chromosome. Conclusion: A wide array of features accompany ring chromosome 8 which have not yet been delineated into a recognizable syndrome.

Background: Niemann-Pick disease Type C (NPC) is a rare genetic lipid storage disorder characterized by heterogeneous clinical presentations primarily affecting the neurological and visceral systems. This study aims to elucidate the clinical manifestations, radiological findings, and genetic characteristics of NPC, emphasizing the implications of familial aggregation and consanguinity. Case Presentation: We present two cases from a single family, detailing the clinical progression, radiological findings, and genetic mutations. Case 1 involves a 39-year-old male exhibiting symptoms such as dysarthria, cerebellar ataxia, and progressive neurological decline over eight years. Case 2, a relative aged five, displays similar early-onset neurological symptoms. Both cases demonstrate significant cerebellar atrophy on MRI and share a familial NPC1 gene mutation, suggesting a hereditary pattern influenced by consanguineous relationships. Whole Exome Sequencing identified a pathogenic homozygous mutation in the NPC1 gene, confirming the diagnosis of NPC. This finding underscores the genetic basis of the disease and highlights the role of familial genetics in its pathogenesis. Conclusion: These cases underscore the critical role of genetic testing, particularly whole exome sequencing, in diagnosing NPC, which can often present with diverse clinical symptoms. The familial clustering observed also draws attention to the genetic counseling needs in populations with high rates of consanguinity, emphasizing the importance of community genetic studies to understand and manage such rare disorders.