A comprehensive review of reported heritable noggin‐associated syndromes and proposed clinical utility of one broadly inclusive diagnostic term: NOG ‐related‐symphalangism spectrum disorder ( NOG ‐SSD)

The NOG gene encodes noggin, a secreted polypeptide that is important for regulating multiple signaling pathways during human development, particularly in cartilage and bone. The hallmark of NOG ‐related syndromes is proximal symphalangism, defined by abnormal fusion of the proximal interphalangeal joints of the hands and feet. Many additional features secondary to NOG mutations are commonly but inconsistently observed, including a characteristic facies with a hemicylindrical nose, congenital conductive hearing loss due to stapes fixation, and hyperopia. The variable clinical presentations led to the designation of five different autosomal dominant syndromes, all subsequently found to have resulted from NOG mutations. These include (1) proximal symphalangism; (2) multiple synostoses syndrome 1; (3) stapes ankylosis with broad thumbs and toes; (4) tarsal‐carpal coalition syndrome; and (5) brachydactyly type B2. Herein, we review the phenotypic features associated with mutations in the NOG gene, demonstrating the overlapping characteristics of these syndromes. Due to the variable phenotypic spectrum within families and among families with the same mutation, we propose a unifying term, NOG ‐related symphalangism spectrum disorder ( NOG ‐SSD), to aid in the clinical recognition and evaluation of all affected individuals with these phenotypes. These NOG gene variants are available in a new locus‐specific database ( https://NOG.lovd.nl ).Hum Mutat 32:1–10, 2011. © 2011 Wiley‐Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87082/1/21515_ftp.pd

“My Plate is Full”: Reasons for Declining a Genetic Evaluation of Hearing Loss

The aim of this study was to obtain patient and parent perspectives on genetic evaluation of hearing loss, in order to identify motivators, expectations, and barriers. Three focus groups were conducted following a semi‐structured discussion guide, led by an independent moderator. Participants were hearing parents of children with permanent hearing loss or deaf adults. Qualitative content analysis was used to develop a codebook and identify major themes and subthemes. Participant views were compared to national guidelines. The 28 participants comprised 23 parents representing 21 unique families and 5 deaf adults. 13/21 families and 0/5 adults reported comorbidities, 4/21 families and 3/5 adults had a positive family history, and 12/21 families versus 0/5 adults had utilized genetics services. A common theme among adults and parents was a curiosity as to the cause of hearing loss. Parents were motivated to detect comorbidities and optimize care for hearing loss. Some parents felt overwhelmed by the hearing loss and unprepared to pursue early genetic evaluation as recommended in guidelines. Several reported positive experiences following genetics consultation, while others reported unease and unmet expectations. Notably, both parents and adults expressed ambivalence regarding the desire for genetic knowledge. Financial concerns and difficulties obtaining a referral were cited as extrinsic barriers. For parents of children with hearing loss, both the presence of comorbidities and a positive family history were drivers of genetics consultation and/or genetic testing. We identified educational opportunities for both patients and providers that would improve informed decision‐making and increase access to genetic services. Consideration of the patient/family perspective and their decision‐making processes, along with flexibility in the approach to genetics evaluation and its timing, will optimize both the development and implementation of guidelines.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147183/1/jgc40597.pd

Validity, discriminative ability, and reliability of the hearing‐related quality of life questionnaire for adolescents

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102684/1/lary24336.pd

Hairy polyp of the pharynx obscured on physical examination by endotracheal tube, but diagnosed on brain imaging

We report a case of hairy polyp of the pharynx diagnosed on brain MRI in order to stress the need to examine carefully all tissues included on an imaging study, even those outside the clinically stated region of interest, and to remind practitioners to consider unusual as well as common etiologies for neonatal respiratory distress. Our case is unique in that thorough examination of a brain MRI, ordered in the evaluation of presumed central apnea, led to the correct diagnosis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46715/1/247_2005_Article_1500.pd

A Dominantly Inherited Progressive Deafness Affecting Distal Auditory Nerve and Hair Cells

We have studied 72 members belonging to a large kindred with a hearing disorder inherited in an autosomal dominant pattern. We used audiological, physiological, and psychoacoustic measures to characterize the hearing disorders. The initial phenotypic features of the hearing loss are of an auditory neuropathy (AN) with abnormal auditory nerve and brainstem responses (ABRs) and normal outer hair cell functions [otoacoustic emissions (OAEs) and cochlear microphonics (CMs)]. Psychoacoustic studies revealed profound abnormalities of auditory temporal processes (gap detection, amplitude modulation detection, speech discrimination) and frequency processes (difference limens) beyond that seen in hearing impairment accompanying cochlear sensory disorders. The hearing loss progresses over 10–20 years to also involve outer hair cells, producing a profound sensorineural hearing loss with absent ABRs and OAEs. Affected family members do not have evidence of other cranial or peripheral neuropathies. There was a marked improvement of auditory functions in three affected family members studied after cochlear implantation with return of electrically evoked auditory brainstem responses (EABRs), auditory temporal processes, and speech recognition. These findings are compatible with a distal auditory nerve disorder affecting one or all of the components in the auditory periphery including terminal auditory nerve dendrites, inner hair cells, and the synapses between inner hair cells and auditory nerve. There is relative sparing of auditory ganglion cells and their axons.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41385/1/10162_2004_Article_5014.pd

Laryngotracheal stenosis in children

The diagnosis of laryngotracheal stenosis should be suspected in children with stridor, feeding difficulties, or atypical croup. Only half of the children with congenital laryngotracheal stenosis require tracheotomy, and many of these children can be decannulated following uncomplicated surgical therapy. In contrast, tracheotomy-dependent patients with acquired laryngotracheal stenosis require more extensive surgical intervention, which should be carried out as early as possible to provide the best opportunity for developing normal oral communication.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42215/1/405-255-1-12_82550012.pd

A PCR-RFLP Assay for the A716T Mutation in the WFS1 Gene, a Common Cause of Low-Frequency Sensorineural Hearing Loss

Nonsyndromic low-frequency sensorineural hearing loss (LFSNHL) is an unusual type of hearing loss that affects frequencies at 2,000 Hz and below. Recently, we reported five different heterozygous missense mutations in the Wolfram syndrome gene, WFS1, found to be responsible for LFSNHL in six families. One of the five mutations, A716T, may be a common cause of LFSNHL, as it has been reported in three families to date (Bespalova et al., 2001; Young et al., 2001). We have developed a PCR-based restriction fragment-length polymorphism (RFLP) assay to detect the A716T mutation in a simple, specific test. This method was evaluated with DNA samples from a family in which the A716T mutation was segregating with LFSNHL. This simple assay successfully detected the presence of the A716T mutation in all of the individuals predicted to be affected, based on audiologic results. Therefore, this assay can be routinely used for initial screening of the A716T mutation in patients with LFSNHL, before screening the entire coding region of the WFS1 gene.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63374/1/109065702761403423.pd

Cummings pediatrics otolaryngology

xii, 411 pages : illustrations ; 28 c