11 research outputs found
Novel Patched 1 mutations in patients with nevoid basal cell carcinoma syndrome - case report
Nevoid basal cell carcinoma syndrome (Gorlin syndrome) is a rare autosomal dominant disorder characterized by numerous basal cell carcinomas, keratocystic odontogenic tumors of the jaws, and diverse developmental defects. This disorder is associated with mutations in tumor suppressor gene Patched 1 (PTCH1). We present two patients with Gorlin syndrome, one sporadic and one familial. Clinical examination, radiological and CT imaging, and mutation screening of PTCH1 gene were performed. Family members, as well as eleven healthy controls were included in the study. Both patients fulfilled the specific criteria for diagnosis of Gorlin syndrome. Molecular analysis of the first patient showed a novel frameshift mutation in exon 6 of PTCH1gene (c.903delT). Additionally, a somatic frameshift mutation in exon 21 (c.3524delT) along with germline mutation in exon 6 was detected in tumor-derived tissue sample of this patient. Analysis of the second patient, as well as two affected family members, revealed a novel nonsense germline mutation in exon 8 (c.1148 C gt A)
Levodopa-refractory hyperprolactinemia and pituitary findings in inherited disorders of biogenic amine metabolism
Elevated serum prolactin concentrations occur in inherited disorders of biogenic amine metabolism because dopamine deficiency leads to insufficient inhibition of prolactin secretion. This work from the International Working Group on Neurotransmitter Related Disorders (iNTD) presents the results of the first standardized study on levodopa-refractory hyperprolactinemia (LRHP; >1000 mU/L) and pituitary magnetic resonance imaging (MRI) abnormalities in patients with inherited disorders of biogenic amine metabolism. Twenty-six individuals had LRHP or abnormal pituitary findings on MRI. Tetrahydrobiopterin deficiencies were the most common diagnoses (n = 22). The median age at diagnosis of LRHP was 16 years (range: 2.5-30, 1st-3rd quartiles: 12.25-17 years). Twelve individuals (nine females) had symptoms attributed to hyperprolactinemia: menstruation-related abnormalities (n = 7), pubertal delay or arrest (n = 5), galactorrhea (n = 3), and decreased sexual functions (n = 2). MRI of the pituitary gland was obtained in 21 individuals; six had heterogeneity/hyperplasia of the gland, five had adenoma, and 10 had normal findings. Eleven individuals were treated with the dopamine agonist cabergoline, ameliorating the hyperprolactinemia-related symptoms in all those assessed. Routine monitoring of these symptoms together with prolactin concentrations, especially after the first decade of life, should be taken into consideration during follow-up evaluations. The potential of slow-release levodopa formulations and low-dose dopamine agonists as part of first-line therapy in the prevention and treatment of hyperprolactinemia should be investigated further in animal studies and human trials. This work adds hyperprolactinemia-related findings to the current knowledge of the phenotypic spectrum of inherited disorders of biogenic amine metabolism
Assessment of intellectual impairment, health-related quality of life, and behavioral phenotype in patients with neurotransmitter related disorders: Data from the iNTD registry
Inherited disorders of neurotransmitter metabolism are a group of rare diseases, which are caused by impaired synthesis, transport, or degradation of neurotransmitters or cofactors and result in various degrees of delayed or impaired psychomotor development. To assess the effect of neurotransmitter deficiencies on intelligence, quality of life, and behavior, the data of 148 patients in the registry of the International Working Group on Neurotransmitter Related Disorders (iNTD) was evaluated using results from standardized age-adjusted tests and questionnaires. Patients with a primary disorder of monoamine metabolism had lower IQ scores (mean IQ 58, range 40-100) within the range of cognitive impairment (<70) compared to patients with a BH4 deficiency (mean IQ 84, range 40-129). Short attention span and distractibility were most frequently mentioned by parents, while patients reported most frequently anxiety and distractibility when asked for behavioral traits. In individuals with succinic semialdehyde dehydrogenase deficiency, self-stimulatory behaviors were commonly reported by parents, whereas in patients with dopamine transporter deficiency, DNAJC12 deficiency, and monoamine oxidase A deficiency, self-injurious or mutilating behaviors have commonly been observed. Phobic fears were increased in patients with 6-pyruvoyltetrahydropterin synthase deficiency, while individuals with sepiapterin reductase deficiency frequently experienced communication and sleep difficulties. Patients with BH4 deficiencies achieved significantly higher quality of life as compared to other groups. This analysis of the iNTD registry data highlights: (a) difference in IQ and subdomains of quality of life between BH4 deficiencies and primary neurotransmitter-related disorders and (b) previously underreported behavioral traits.Dietmar Hopp Stiftung (DE); Medical Faculty of the University of Heidelberg
Parasitic Twin Presenting Rudimentary Upper Limbs Causes a Unique Spectrum of Anomalies of Autosite
Autism and Hypoplastic Corpus Callosum in a Case of Monocentric Marker Chromosome 15
An 8-year-old boy was diagnosed with autism, along with development delay, seizures, and hypoplastic corpus callosum. His karyotype was 47, XY, +mar.ish (15) (D15Z1+, SNRPN+, GABRB3+, PML-(de novo?). The supernumerary marker chromosome 15 with euchromatin was monosatellited and monocentric. Although autism, seizures, and mental and developmental retardation are not rare in association with a dicentric, bisatellited supernumerary marker chromosome 15, the present case is novel for a monocentric, monosatellited supernumerary marker chromosome 15 and the additional feature of hypoplastic corpus callosum. The present case provides support for the hypotheses that additional copies of different segments of proximal 15q are related to autism and to malformations of corpus callosum. (C) 2009 by Elsevier Inc. All rights reserved
Assessment of intellectual impairment, health-related quality of life, and behavioral phenotype in patients with neurotransmitter related disorders: Data from the iNTD registry
Inherited disorders of neurotransmitter metabolism are a group of rare
diseases, which are caused by impaired synthesis, transport, or
degradation of neurotransmitters or cofactors and result in various
degrees of delayed or impaired psychomotor development. To assess the
effect of neurotransmitter deficiencies on intelligence, quality of
life, and behavior, the data of 148 patients in the registry of the
International Working Group on Neurotransmitter Related Disorders (iNTD)
was evaluated using results from standardized age-adjusted tests and
questionnaires. Patients with a primary disorder of monoamine metabolism
had lower IQ scores (mean IQ 58, range 40-100) within the range of
cognitive impairment (<70) compared to patients with a BH4 deficiency
(mean IQ 84, range 40-129). Short attention span and distractibility
were most frequently mentioned by parents, while patients reported most
frequently anxiety and distractibility when asked for behavioral traits.
In individuals with succinic semialdehyde dehydrogenase deficiency,
self-stimulatory behaviors were commonly reported by parents, whereas in
patients with dopamine transporter deficiency, DNAJC12 deficiency, and
monoamine oxidase A deficiency, self-injurious or mutilating behaviors
have commonly been observed. Phobic fears were increased in patients
with 6-pyruvoyltetrahydropterin synthase deficiency, while individuals
with sepiapterin reductase deficiency frequently experienced
communication and sleep difficulties. Patients with BH4 deficiencies
achieved significantly higher quality of life as compared to other
groups. This analysis of the iNTD registry data highlights: (a)
difference in IQ and subdomains of quality of life between BH4
deficiencies and primary neurotransmitter-related disorders and (b)
previously underreported behavioral traits