Cooccurrence of Two Different Genetic Diseases: A Case of Valproic Acid Hepatotoxicity in Nicolaides-Baraitser Syndrome (SMARCA2 Mutation)-Due to a POLG1-Related Effect?

Nicolaides-Baraitser syndrome (NCBRS) is a rare disease caused by a mutation in the SMARCA2 gene. Clinical features include craniofacial dysmorphia and abnormalities of the limbs, as well as intellectual disorder and often epilepsy. Hepatotoxicity is a rare complication of the therapy with valproic acid (VPA) and a mutation of the polymerase γ (POLG) might lead to a higher sensitivity for liver hepatotoxicity. We present a patient with the coincidence of two rare diseases, the NCBRS and additionally a POLG1 mutation in combination with a liver hepatotoxicity. The co-occurrence in children for two different genetic diseases is discussed with the help of literature review.

Further characterization of CAPOS/CAOS syndrome with the Glu818Lys mutation in the ATP1A3 gene: A case report.

A 38-year-old female patient experienced recurrent episodes of neurological deterioration during febrile illness at the age of 7 and 8 months, and 2, 4, and 37 years. Acute symptoms comprised unconsciousness, headache, abnormal ocular movements, flaccid paralysis with areflexia, ataxia, dysphagia, and movement disorders. Each episode of neurological deterioration was followed by partial recovery with residual symptoms of progressive disturbance of visual acuity with optic atrophy and hearing loss, moderate intellectual disability, strabismus, ophthalmoplegia, as well as fluctuating degree of gait ataxia, chorea, tremor, and myoclonus. In addition, electrocardiography revealed incomplete right bundle branch block. The genetic testing revealed a de novo heterozygous mutation of c.2452G > A (p.Glu818Lys) in the ATP1A3 gene, which was compatible with the clinical phenotype of CAPOS (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss)/CAOS syndrome. Here we discuss the significance of clinical features of a patient, overlapping with those of alternating hemiplegia of childhood, along with a literature review.

[Vismodegib for basal cell carcinoma: targeted therapy in case of locally advanced or metastasised disease]. / Vismodegib voor gevorderd basaalcelcarcinoom.

The development of the hedgehog pathway inhibitor vismodegib provides a new treatment option for metastasised and locally advanced basal cell carcinoma in which surgical excision or radiotherapy is contraindicated. Only a fraction of patients with basal cell carcinoma are eligible for this therapy, but it is effective in the majority of those who do receive vismodegib. However, development of tumour resistance is quite common and adverse events frequently lead to discontinuation of therapy. Intermittent treatment or combination therapy could reduce the occurrence of tumour resistance and diminish toxicity. We present three patients who were successfully treated with vismodegib: a 73-year-old man with locally advanced basal cell carcinoma, an 82-year-old man with basal cell carcinoma that had metastasised to the lungs, and a 42-year-old man with Gorlin syndrome.

Congenital dyserythropoietic anemia type I with bone abnormalities, mutations of the CDAN I gene, and significant responsiveness to alpha-interferon therapy.

Congenital dyserythropoietic anemia type I (CDA I) is a rare autosomal recessive disorder with ineffective erythropoiesis, characteristic morphological abnormalities of erythroblasts, and iron overloading. CDA I is caused by mutations in the CDAN I gene, encoding a protein named codanin-1. Complex bone abnormalities, especially syndactyly, have not been systematically described with this disease. We present two cases of morphologically and genetically confirmed CDA I with striking bone abnormalities and response to treatment with alpha-interferon. Our cases clearly document the association of skeletal anomalism with CDA I and indicate that codanin-1 may play a role in the development of the skeleton.

[Calcaneal spur]. / Shpora piatochnoi kosti.

The clinical picture, diagnosis, and treatment of calcaneal spurs are described on the basis of 190 cases (102 females and 88 males whose ages ranged from 38 to 79 years). All were treated by local administration of various steroid hormones. A good immediate result was produced by a single administration of the hormone in 90% of cases; the favourable result persisted in the late-term periods in 78 persons. The author claims hormone therapy to be the most effective among all the known methods of nonoperative treatment of calcaneal spurs and recommends it for a wide surgical practice.