Congenital Hypotonia: Cracking a SAGA of consanguineous kindred harboring four genetic variants.

BACKGROUND: We aimed to determine the molecular and biochemical basis of an extended highly consanguineous family with multiple children presenting severe congenital hypotonia. METHODS: Clinical investigations, homozygosity mapping, linkage analyses and whole exome sequencing, were performed. mRNA and protein levels were determined. Population screening was followed. RESULTS: We have identified a novel nonsense variant in NGLY1 in two affected siblings, and compound heterozygosity for three novel RYR1 variants in two affected sisters from another nuclear family within the broad pedigree. Population screening revealed a high prevalence of carriers for both diseases. The genetic variants were proven to be pathogenic, as demonstrated by western blot analyses. CONCLUSIONS: Revealing the genetic diagnosis enabled us to provide credible genetic counselling and pre-natal diagnosis to the extended family and genetic screening for this high-risk population. Whole exome/genome sequencing should be the first tier tool for accurate determination of the genetic basis of congenital hypotonia. Two different genetic disorders within a large consanguineous pedigree should be always considered.

The significance of bradycardia in anorexia nervosa.

Anorexia nervosa (AN) is a life-threatening condition, with a significant risk for death, due to cardiovascular complications. It is characterized by abnormal eating behavior and has the highest mortality rate of all psychiatric disorders. It has been associated with bradycardia (a heart rate [HR] of less than 60 beats per minute) (up to 95%), hypotension, mitral valve prolapse, and heart failure. The diagnosis of AN can be elusive, and more than half of all cases are undetected. The purpose of this study was to raise and improve awareness to the possible diagnosis of AN in adolescent and young adult patients with weight loss displaying bradycardia and new cardiac disorders. Clinical characteristics, HR, and electrocardiographic data of 23 consecutive patients (20 females) with AN and of 10 young adults (8 females) without AN, between the years 2006 and 2009, were recorded and summarized. At presentation 16/23 (69.6%) showed HR < 50 bpm. The mean lowest HR of all patients was 44 ± 6 (range 26 to 68) bpm. No patient needed pacemaker therapy. Bradycardia in young adults, especially females with weight loss, should raise the possible diagnosis of AN, so it can be treated early in-time, and thus prevent premature death.

Diagnostic evaluation of foreign body aspiration in children: a prospective study.

AIM: The aim of this study was to evaluate the yield of clinical symptoms, signs, and radiological studies in the diagnosis of foreign body aspiration (FBA) in children. METHODS: During the 2-year study, we performed on all children admitted to the pediatric department for suspected FBA a protocol that included the following: thorough medical history, physical examination, radiological studies (chest x-ray and fluoroscopy), and rigid bronchoscopy by a senior otolaryngologist. The yield of these measures for the diagnosis of FBA was evaluated. RESULTS: Foreign bodies were found in 56 (57%) of the 98 children with suspected FBA. Thirty-three (59%) children were boys and 23 (41%) girls (P < .05), with a mean age of 24 months (range, 8-84 months). Main symptoms in the children with FBA were the following: choking (76.8%), prolonged cough (14.3%), dyspnea (3.6%), and nonresolving pneumonia (1.8%). Physical examination, chest x-ray, and fluoroscopy findings were abnormal in 80.4%, 67.9%, and 46.9% of the children with FBA, respectively. The diagnostic yield of physical examination and radiological studies increased 24 hours after the event of FBA. In 45.2% of the children with positive history but with normal findings from physical examination and radiological studies, foreign bodies were found. Of the children with "doubtful" history, physical examination, chest x-ray, and fluoroscopy findings were abnormal in 58%, 38%, and 12.5%, respectively. Foreign bodies were found in 9.5% of these children. CONCLUSION: Medical history is the key for the diagnosis of FBA. Choking followed by an acute episode of coughing is the most common presentation of FBA. The yield of physical examination and radiological studies in the diagnosis of FBA is relatively low but is increased when the presentation is delayed and when history is doubtful. If FBA is suspected, bronchoscopy should be performed.