Bleeding and non-bleeding phenotypes in patients with GGCX gene mutations

Functional limitations for the vitamin K cycle, caused either by mutations in gamma-glutamyl carboxylase or vitamin K epoxide reductase genes, result in hereditary deficiency of vitamin K-dependent coagulation factors (VKCFD1 and VKCFD2, respectively). Patients suffering from VKCFD often share several other anatomical irregularities which are not related to haemostasis. Here we report on nine patients, eight of them previously unreported, who presented with VKCFD1. All were examined with special attention to vitamin K-dependent coagulation factors as well as to bone and heart development and to other anatomical signs of embryonal vitamin K deficiency. In total, we detected ten mutations in the gamma-glutamyl carboxylase gene of which seven have not been previously reported. Most interestingly, additional non-bleeding phenotypes were observed in all patients including midfacial hypoplasia, premature osteoporosis, cochlear hearing loss, heart valve defects, pulmonary stenosis, or pseudoxanthoma elasticum-like phenotype. Undercarboxylated matrix Gla protein, osteocalcin, and periostin appear to be responsible for these defects which are also observed in cases of fetal warfarin syndrome.     

Clinical findings in patients with acoustic neurinoma

Herein we review the symptoms, physical findings, and test results in 131 patients with acoustic neurinoma. The earliest symptoms are unilateral hearing loss, tinnitus, and dysequilibrium. As the disease progresses, facial numbness, facial weakness, and headaches become more prominent. Physical findings other than hearing loss are uncommon; the most frequently observed are a decreased corneal reflex, nystagmus, and facial hypoesthesia. Routine audiometry provides objective information about the hearing loss. Some degree of asymmetry is found in the pure-tone tests. In addition, the speech discrimination scores are frequently lower than expected. Special audiometric tests should be performed on those patients with residual hearing; at the present time, acoustic reflex tests and the brainstem-evoked response yield the most information. Computed tomography with dye enhancement with or without the use of air contrast has become the most accurate roentgenographic test. Our goal is to identify acoustic neurinomas sufficiently early so that surgical removal is safe and leaves minimal deficit.     

Do children with Williams syndrome really have good vocabulary knowledge? Methods for comparing cognitive and linguistic abilities in developmental disorders

The comparison of cognitive and linguistic skills in individuals with developmental disorders is fraught with methodological and psychometric difficulties. In this paper, we illustrate some of these issues by comparing the receptive vocabulary knowledge and non‐verbal reasoning abilities of 41 children with Williams syndrome, a genetic disorder in which language abilities are often claimed to be relatively strong. Data from this group were compared with data from typically developing children, children with Down syndrome, and children with non‐specific learning difficulties using a number of approaches including comparison of age‐equivalent scores, matching, analysis of covariance, and regression‐based standardization. Across these analyses children with Williams syndrome consistently demonstrated relatively good receptive vocabulary knowledge, although this effect appeared strongest in the oldest children.