-
1.
Increased creatine demand during pregnancy in Arginine: Glycine Amidino-Transferase deficiency: a case report.
Alessandrì, MG, Strigini, F, Cioni, G, Battini, R
BMC pregnancy and childbirth. 2020;(1):506
Abstract
BACKGROUND Creatine (Cr), an amino acid derivative, is one of the most important sources of energy acting as both a spatial and temporal energy buffer through its phosphorylated analogue phosphocreatine (PCr) and creatine kinase (CK). Maternal Cr biosynthesis and metabolism seem to play an important role in pregnancy, as shown in preclinical and in healthy human pregnancy studies. Patients with Arginine:Glycine Amidino-Transferase deficiency (AGAT-d), due to the deficit of the first enzyme involved in Cr synthesis, are at a disadvantage due to their failure to synthesize Cr and their dependence on external intake, in contrast to normal subjects, where changes in Cr biosynthesis supply their needs. We report the outcomes of a pregnancy in an AGAT-d woman, and the challenge we faced in managing her treatment with oral Cr to ensure optimal conditions for her fetus. CASE PRESENTATION A 22-year-old AGAT-d woman referred to our Institute for the management of her first conception at 11 weeks of fetal gestational age. Sonographic monitoring at 20 w GA indicated a reduction of fetal growth, in particular of the head circumference that was below the 3rd centile. Biochemical monitoring of Cr in biological fluids of the mother revealed a decline of the Cr concentrations, in particular in the urine sample, requiring prompt correction of the Cr dose. At 35 weeks of gestation the patient delivered a male infant, heterozygous for GATM mutation, with normal brain Cr levels; at one year the baby achieved typical developmental milestones. CONCLUSIONS This rare pregnancy demonstrates that Cr levels in the blood and urine of the mother with AGAT-d decreased since the first months of gestation. The increase of the Cr daily dose administered to the mother seems to have produced beneficial effects also on the fetus.
-
2.
Bosch-Boonstra-Schaaf Optic Atrophy Syndrome Presenting as New-Onset Psychosis in a 32-Year-Old Man: A Case Report and Literature Review.
Hobbs, MM, Wolters, WC, Rayapati, AO
Journal of psychiatric practice. 2020;(1):58-62
Abstract
Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is a recently described autosomal dominant disorder caused by mutations in the nuclear receptor subfamily 2 group F member 1 (NR2F1) gene. Its common features include optic atrophy and/or hypoplasia, developmental delay, intellectual disability, attention deficit disorder, autism spectrum disorder, seizures, hearing defects, spasticity, hypotonia, and thinning of the corpus callosum. Mitochondrial involvement has also been described with BBSOAS. Currently, 31 cases of BBSOAS have been described in the literature. Here we report a case of undiagnosed BBSOAS presenting as psychosis in a 32-year-old man with a history of bilateral optic nerve atrophy, intellectual disability, epilepsy, and mitochondrial complex I abnormality on muscle biopsy. Whole-genome sequencing identified a heterozygous de novo nonsense mutation in the NR2F1 gene [c.253 G>T (guanine to thymine mutation in coding position 253) in exon 1, p.E85X variant (GAG>TAG) (glutamic acid to stop codon mutation; protein truncated to 85 amino acids)]. A pathogenic nonsense mutation has not previously been reported in the literature in association with BBSOAS and represents an expansion of clinically relevant variants. Psychosis has also not been previously reported in this syndrome and may represent a phenotypic expansion of BBSOAS, a manifestation of prolonged disease, or a result of disease management.
-
3.
One-month-old girl presenting with pseudohypoaldosteronism leading to the diagnosis of CDK13-related disorder: a case report and review of the literature.
Yakubov, R, Ayman, A, Kremer, AK, van den Akker, M
Journal of medical case reports. 2019;(1):386
Abstract
BACKGROUND It is not uncommon that an infant with a disease of unknown etiology is presented to a physician. Facial dysmorphic features lead to a different diagnosis. It is a challenge to link the presentation to the newfound diagnosis. CASE PRESENTATION A 37-day-old Yemenite Jewish girl was presented to our institution with a clinical picture of pseudohypoaldosteronism due to abnormal facial features and a psychomotor developmental delay. Further investigation led to the diagnosis of CDK13-related disorder. According to the literature, CDK13 has a key role in the cell cycle, but no interference with the aldosterone signaling pathway or electrolyte balance was described. No mutations in the previously described gene NR3C2 (cytogenetic location 4q31.23), encoding the mineralocorticoid receptor, were found. Although the clinical presentation corresponded to pseudohypoaldosteronism type 1, we could not genetically confirm this. CONCLUSIONS Probably pseudohypoaldosteronism was a coincidental finding in this girl with a CDK13 mutation, but because only limited information is known about CDK13-related disorders, further investigation could be more informative to clarify this presentation.
-
4.
Phenotypic heterogeneity of intellectual disability in patients with congenital insensitivity to pain with anhidrosis: A case report and literature review.
Liu, Z, Liu, J, Liu, G, Cao, W, Liu, S, Chen, Y, Zuo, Y, Chen, W, Chen, J, Zhang, Y, et al
The Journal of international medical research. 2018;(6):2445-2457
Abstract
Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive heterogeneous disorder mainly caused by mutations in the neurotrophic tyrosine receptor kinase 1 gene ( NTRK1) and characterized by insensitivity to noxious stimuli, anhidrosis, and intellectual disability. We herein report the first north Han Chinese patient with CIPA who exhibited classic phenotypic features and severe intellectual disability caused by a homozygous c.851-33T>A mutation of NTRK1, resulting in aberrant splicing and an open reading frame shift. We reviewed the literature and performed in silico analysis to determine the association between mutations and intellectual disability in patients with CIPA. We found that intellectual disability was correlated with the specific Ntrk1 protein domain that a mutation jeopardized. Mutations located peripheral to the Ntrk1 protein do not influence important functional domains and tend to cause milder symptoms without intellectual disability. Mutations that involve critical amino acids in the protein are prone to cause severe symptoms, including intellectual disability.
-
5.
[A novel mutation in KCNB1 gene in a child with neuropsychiatric comorbidities with both intellectual disability and epilepsy and review of literature].
Miao, P, Peng, J, Chen, C, Gai, N, Yin, F
Zhonghua er ke za zhi = Chinese journal of pediatrics. 2017;(2):115-119
Abstract
Objective: To explore the association between the phenotype and KCNB1 gene mutation. Method: Clinical information including physical features, laboratory and genetic data of one patient of mental retardation with refractory epilepsy from Department of Pediatrics, Xiangya Hospital in January 2016 was analyzed. This patient was discovered to have KCNB1 gene mutations through whole exome sequencing. Relevant information about KCNB1 gene mutation was searched and collected from Pubmed, CNKI, Human Gene Mutation Database(HGMD) and Online Mendelian Inheritance in Man(OMIM). Searching was done using "KCNB1" as a keyword. Result: A 3.5 years old boy who visited our hospital firstly at the age of 2 years because of development delay came for follow up as he developed seizures.The forms included tonic, clonic seizures and spasm. The condition became more severe 10 months later. Electroencephalogram(EEG) showed high frequency discharge (>85%). He had poor response to multiple anti-epileptic drugs, methylprednisolone and ketogenic diet. At the age of 3, he started to have mental regression. Whole exome-sequencing study (trios) identified a novel heterozygous mutation c. G1136T (p.G379V) in KCNB1, which is not available in the databases mentioned above. This is the first case report of KCNB1 gene mutation in China. Eight cases have been reported so far worldwide and all of them were diagnosed with refractory epilepsy. Those 8 reported cases of encephalopathy were all due to de novo mutation. Conclusion: The main clinical features of patients with KCNB1 mutations include severe to profound intellectual disability, intractable seizures, hypotonia and regression of cognition and motor activity which lead to poor prognosis.
-
6.
[Dravet syndrome as a cause of epilepsy and learning disability].
Lund, C, Bremer, A, Lossius, MI, Selmer, KK, Brodtkorb, E, Nakken, KO
Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke. 2012;(1):44-7
Abstract
BACKGROUND Dravet syndrome is a severe, genetic epileptic encephalopathy with seizures starting during the first year of life. We present a review of the genetic and clinical picture along with treatment aspects. MATERIAL AND METHODS This review is based on a non-systematic literature search in PubMed until April 2011 and the personal experiences of the authors. RESULTS Dravet syndrome should be suspected in children with febrile hemiconvulsions or tonic-clonic seizures in the first year of life. Non-febrile seizures also occur, and other seizure types gradually appear, e.g. myoclonic jerks, atypical absences or focal seizures. In adulthood the clinical picture is less characteristic. The clinical diagnosis is supported by genetic testing; 70-80% of the patients have mutations in the sodium channel subunit gene SCN1A. Seizure control is difficult to achieve, but valproate, benzodiazepines and stiripentol may cause improvement, whereas sodium channel blockers, such as lamotrigine and carbamazepine may aggravate the tendency towards seizures. INTERPRETATION Dravet syndrome appears to be an under-recognised condition among both children and adults with severe epilepsy and learning disability. Clinical information from the first years of life is essential in making the diagnosis. A correct diagnosis at an early age is essential for appropriate treatment and genetic counselling.
-
7.
Ring 21 chromosome presenting with epilepsy and intellectual disability: clinical report and review of the literature.
Specchio, N, Carotenuto, A, Trivisano, M, Cappelletti, S, Digilio, C, Capolino, R, Di Capua, M, Fusco, L, Vigevano, F
American journal of medical genetics. Part A. 2011;(4):911-4
-
8.
[Reflections on mental retardation and congenital hypothyroidism: effects of trace mineral deficiencies].
Sidibé, el H
Sante (Montrouge, France). 2007;(1):41-50
Abstract
While deficiencies of trace minerals and vitamins are rare in humans eating a variety of food, they can occur in premature infants and those with disturbances in dietary behavior for physical or psychological reasons and during parenteral or enteral nutrition. Some deficiencies - such as iron and iodine - cause such serious specific disorders that they must be considered separately. Congenital hypothyroidism induced by iodine deficiency is a major problem. Its public health importance comes from the neurological complications that lead to the most severe forms of endemic congenital hypothyroidism (cretinism). In areas without iodine deficiency, the standard incidence of this disease in the West is 1/4,500 live births. In areas with iodine deficiency, however, its incidence varies from 1 to 5%! It is nonetheless underestimated, because the screening methods revolutionized 20 years ago are still not applied systematically. Additional factors include the thiocyanates in cassava, the selenium deficiency resulting in selenium-dependent glutathione peroxidase deficiency, and the natural goitrogens in some foods: milk, millet, walnuts, and bacterial and chemical water pollutants. Adolescents and adults need 100 microg/day, children aged 1-10 years 60-100 microg, and babies under one year, 35-40 microg, but these daily requirements are not necessarily met. This threat weighs on a billion people, 50-100 million in Europe, especially pregnant women, fetuses, newborns, and young children whose cerebral development may be negatively affected in the womb and in early life. According to some authors, subjects with cretinism syndrome should be found in places where goiter prevalence exceeds 20%. Evaluation of diffuse intellectual impairment in the population would require tools too specific for most studies. Generations of children are the victims throughout wide swaths of the African ecosystem in which it is endemic and associated with poor adaptation to the environment. But studies of isolated places cannot be transposed to entire populations. Because pregnancy in women with hypothyroidism is often thought to have a very negative prognosis, the two cases we report merit attention. In one case, despite certainly insufficient thyroid hormone replacement treatment, the child was born alive and healthy. In the second case, where hypothyroidism followed a thyroidectomy in a woman with Graves disease, a hydrocephalic child was liveborn, without any replacement treatment. In her next pregnancy, she received optimal hormonal treatment and delivered a healthy liveborn child. The disorders due to severe iodine deficiency did not affect our two patients. In a series of 166 cases of congenital hypothyroidism in newborns, only two cases had maternal antithyroid antibodies. Elsewhere, 9 women with hypothyroidism had 11 pregnancies, 9 normal children, 1 premature child (mother had eclampsia), and 1 with Down syndrome and an Ostium primum defect (mother aged 41 years). Ontogenesis of the hypothalamo-pituitary-thyroid axis of the fetus still appears today to develop independently of the mother in cases of hypothyroidism. An important role is played by type III deiodinase, which is especially active in the placenta during pregnancy, probably involving the T3 activity on nuclear and also mitochondrial receptors. The maturation of these receptors is not well understood.
-
9.
Atypical ZFHX1B mutation associated with a mild Mowat-Wilson syndrome phenotype.
Zweier, C, Horn, D, Kraus, C, Rauch, A
American journal of medical genetics. Part A. 2006;(8):869-72
Abstract
Mowat-Wilson syndrome is a recently delineated severe mental retardation, multiple congenital anomalies syndrome caused by dominant nonsense or frameshift mutations, deletions or translocations of the zinc finger homeobox 1B gene (ZFHX1B). We report on a patient with exceptional mild phenotype caused by a novel and unusual splice mutation in the 5'UTR. The aberrant transcript leads to usage of an alternative upstream start codon. The resulting protein differs from the wild-type only in the first 24 amino acids. The aberrant protein therefore contains all known functional domains, but might lack a so far unrecognized putative N-terminal acylation site, which is probably important for neuronal function and facial structures.
-
10.
Clinical report of a pure subtelomeric 1qter deletion in a boy with mental retardation and multiple anomalies adds further evidence for a specific phenotype.
van Bever, Y, Rooms, L, Laridon, A, Reyniers, E, van Luijk, R, Scheers, S, Wauters, J, Kooy, RF
American journal of medical genetics. Part A. 2005;(1):91-5
Abstract
Deletions of the 1q telomere have been reported in several studies screening for subtelomeric rearrangements. However, an adequate clinical description is available from only a few patients. We provide a clinical description of a patient with a subtelomeric deletion of chromosome 1q, previously detected by us in a screening study. Comparison of the clinical presentation of our patient with rare cases reported previously provides further evidence for a specific phenotype of 1q patients, including mental retardation, growth retardation, sometimes with prenatal onset, progressive microcephaly, seizures, hand and foot abnormalities and a variety of midline defects, including corpus callosum, cardiac, genital and gastro-esophageal abnormalities. This clinical presentation is reminiscent of that of patients with larger, microscopically visible deletions of chromosome 1q (>3 Mb) characterized by growth and mental retardation, coarse faces with thin upper lip, epilepsy, and variable other anomalies. In addition, the breakpoint region was mapped to a 26 kb region within the RGS7 gene. Among the 17 known genes in the candidate region, are zinc-finger genes. Other members of this gene family have been implicated in different forms of mental retardation.