Case Reports in Genetics最新文献

Shprintzen-Goldberg craniosynostosis syndrome (SGS) is a rare autosomal dominant condition that was first documented in literature in 1982. The disorder is caused by pathogenic variants in the proto-oncogene SKI gene, a known suppressor of TGF-β activity, located on chromosome 1p36. There is considerable phenotypic overlap with Marfan and Loeys-Dietz syndromes. Common clinical features of SGS include craniosynostosis, marfanoid habitus, hypotonia, dysmorphic facies, cardiovascular anomalies, and other skeletal and connective tissue abnormalities. Ocular manifestations may include hypertelorism, downslanting palpebral fissures, proptosis, myopia, and ectopia lentis. We describe a 25-year-old male with the syndrome. Genetic analysis revealed a novel c.350G>A (p.Arg117His) de novo variant, which was predicted to be pathogenic by the CTGT laboratory. The patient presented with dysmorphic features, marfanoid habitus, severe joint contractures, mitral valve insufficiency, aortic root dilatation, and a history of seizures. His ocular manifestations included hypertelorism, downslanting palpebral fissures, bilateral ptosis, and high myopia. Ophthalmic manifestations are an integral component of the syndrome; however, they have not been well characterized in the literature. From a systematic review of previously published cases to date, we summarize the eye and ocular adnexa manifestations reported.

Amelogenesis imperfecta (AI) represents rare tooth anomalies that affect the quality and/or quantity of the enamel. Clinical phenotypes display a wide spectrum, ranging from mild color changes to severe structural alterations with daily pain. However, all affect the quality of life because of mechanical, psychological, esthetic, and/or social repercussions. Several gene mutations have been linked to AI as a nonsyndromic (isolated) phenotype or a wider syndrome. This case report aimed to present a family with dental structure anomalies followed up in the dental department of the Louis Mourier Hospital (APHP, France) for their extremely poor dental condition. The proband and his mother were clinically diagnosed with AI, and genetic analysis revealed an already described variant in DLX3. Then, the family was further examined for tricho-dento-osseous syndrome. This report illustrates the challenge of diagnosing dental structure anomalies, specifically AI, in adults and highlights the need for an accurate and accessible molecular diagnosis for those anomalies to discriminate between isolated and syndromic pathologies.

SATB2-associated syndrome is an autosomal dominant, multisystemic disorder with associated sleep and behavioral abnormalities. Evidence is limited on appropriate management strategies in this population. We describe the medical management of a four-year-old child with poor sleep and significant behavioral problems. After failing initial treatment with melatonin, we initiated treatment clonidine along with high doses of trazodone for sleep. Daytime treatment with quetiapine was added to successfully manage behavioral issues. We present the challenges associated with treatment strategies in children with this syndrome.

Copy number variations (CNVs) involving the JAG1 gene are rare and infrequently reported in the scientific literature. Recently, a generally healthy young patient presenting with a history of behavioural concerns was referred to us. Herein, we discuss the patient, a 7-year-old female possessing a 0.797 Mb microduplication within the short arm of chromosome 20 at band 12.2. The patient generates considerable curiosity due to the rarity of her case, which includes a de novo partial duplication involving the JAG1 gene. The patient exhibits a wide range of symptoms including facial dysmorphism (dolichocephaly, round face, tented philtrum, anteverted nares, and micrognathia), clinodactyly, and an inborn congenital heart defect. She presented with behavioural concerns including ADHD-I, SPD, motor clumsiness, and poor self-regulation. Deletions in JAG1 are often linked to Alagille Syndrome; however, complete duplications have not been specifically identified as disease-causing. JAG1 mutations are reported alongside various clinical features including facial dysmorphology, heart defects, vertebral abnormalities, and ocular dysmorphic features (strabismus, epicanthal folds, and slanted palpebral fissures). This particular microduplication is rare, and thus, limited data exist regarding its significance. To our knowledge, most reported duplications are larger than 0.797 Mb. This may define a critical region causing phenotypical changes in some patient cases.

While the urea cycle disorders (UCDs) classically present in the neonatal stage, they have become increasingly recognized as a rare cause of unexplained hyperammonemic encephalopathy in adults. Many metabolic triggers for late-onset UCDs have been described in the literature including excessive protein intake. In this case series, ten such documented cases are reviewed with analysis of patient demographic, protein load, treatment course, and patient outcome. Common delays in treatment include recognition of hyperammonemia as the cause of encephalopathy and initiation of hemodialysis. In only one case was a diet history used to raise suspicion for a metabolic derangement. Metabolic disorders remain an important consideration in adults presenting with encephalopathy not explained by more common etiologies, and recent and remote dietary history may provide valuable information.

Background: The ATP-binding cassette, subfamily D, member 1 (ABCD1) protein is a peroxisomal half-transporter that allows for very long chain fatty acid (VLCFA) degradation. Pathogenic variants of ABCD1 cause VLCFAs to build up in various tissues and bodily fluids, resulting in a disorder called X-linked adrenoleukodystrophy (X-ALD). This disorder is most commonly marked by adrenocortical insufficiency and high VLCFA concentration, and has varying levels of neurological involvement depending on phenotype. For example, the Addison-only form of X-ALD has no neurological impact, while the cerebral form of X-ALD often causes severe sensory loss, motor function impairment, cognitive decline, and death.

Methods: A newly characterized and suspected pathogenic variant in ABCD1 cause VLCFAs to build up in various tissues and bodily fluids, resulting in a disorder called X-linked adrenoleukodystrophy (X-ALD). This disorder is most commonly marked by adrenocortical insufficiency and high VLCFA concentration, and has varying levels of neurological involvement depending on phenotype. For example, the Addison-only form of X-ALD has no neurological impact, while the cerebral form of X-ALD often causes severe sensory loss, motor function impairment, cognitive decline, and death.

Results: A case of adult onset adrenomyeloneuropathy (AMN) and a novel ABCD1 cause VLCFAs to build up in various tissues and bodily fluids, resulting in a disorder called X-linked adrenoleukodystrophy (X-ALD). This disorder is most commonly marked by adrenocortical insufficiency and high VLCFA concentration, and has varying levels of neurological involvement depending on phenotype. For example, the Addison-only form of X-ALD has no neurological impact, while the cerebral form of X-ALD often causes severe sensory loss, motor function impairment, cognitive decline, and death.

Conclusions: Data fusion from multiple sources was combined in a comprehensive approach yielding an enriched assessment of the patient's disease and prognosis. Molecular modeling was performed on the variant to better characterize its clinical significance and confirm pathogenicity.

Ring chromosome 20 (r20) is characterized by intellectual impairment, behavioral disorders, and refractory epilepsy. We report a patient presenting nonmosaic ring chromosome 20 followed by duplication and deletion in 20q13.33 with seizures, delayed neuropsychomotor development and language, mild hypotonia, low weight gain, and cognitive deficit. Chromosomal microarray analysis (CMA) enabled us to restrict a chromosomal segment and thus integrate clinical and molecular data with systems biology. With this approach, we were able to identify candidate genes that may help to explain the consequences of deletions in 20q13.33. In our analysis, we observed five hubs (ARFGAP1, HELZ2, COL9A3, PTK6, and EEF1A2), seven bottlenecks (CHRNA4, ARFRP1, GID8, COL9A3, PTK6, ZBTB46, and SRMS), and two H-B nodes (PTK6 and COL9A3). The candidate genes may play an important role in the developmental delay and seizures observed in r20 patients. Gene ontology included microtubule-based movement, nucleosome assembly, DNA repair, and cholinergic synaptic transmission. Defects in these bioprocesses are associated with the development of neurological diseases, intellectual disability, neuropathies, and seizures. Therefore, in this study, we can explore molecular cytogenetic data, identify proteins through network analysis of protein-protein interactions, and identify new candidate genes associated with the main clinical findings in patients with 20q13.33 deletions.

The classic Rubinstein-Taybi syndrome Type 1 (RSTS1, OMIM 180849) is caused by heterozygous mutations or deletions of the CREBBP gene. Herein, we describe the case of a Saudi boy with chromosome 16p13.3 contiguous gene deletion syndrome (OMIM 610543) including the SLX4, DNASE1, TRAP1, and CREBBP genes, but presenting with a relatively mild RSTS1 syndrome phenotype. Compared with previously reported cases with severe phenotypes associated with 16p13.3 contiguous gene deletions, our patient had partial deletion of the CREBBP gene (with a preserved 5' region), which might explain his relatively mild phenotype.

Adrenoleukodystrophy (ALD) is an X-linked peroxisomal disorder with classical features, which can be also recognised in a low resource setting. It had been described in various populations across the globe, but very few cases have been reported from Africa. In a boy with features of a progressive central nervous system condition and adrenal failure, ABCD1 gene screening was performed based on a clinical history and basic radiological features which were compatible with ALD. A common ABCD1 mutation was identified in this patient, which is the first report of genetically confirmed ALD in Sub-Saharan Africa. ALD is likely under recognised in those areas where there is no neurologist. This genetic confirmation widens geographical distribution of ABCD1-associated disease, and illustrates recognisability of this disorder, even when encountered in a low-resource environment.