Location of facioscapulohumeral muscular dystrophy gene on chromosome 4

Disorders of Keratinization

The erythrokeratodermas (EKs) are a group of disorders characterized by erythematous plaques associated with variable features that include palmoplantar keratoderma. One type of EK is known as "progressive symmetric erythrokeratoderma" (PSEK). We studied members of a family of Japanese origin in which the index case with PSEK had had well-demarcated nonmigratory erythematous plaques on her extremities since birth. Sequence determination of the loricrin gene revealed an insertion of a C following nucleotide 709. The mutation results in a frameshift that changes the terminal 91 amino acids in the wild-type polypeptide into missense amino acids and adds 65 additional residues. This further implicates loricrin defects in the pathogenesis of disorders with palmoplantar keratoderma and pseudoainhum.

https://www.cell.com/ajhg/pdf/S0002-9297(07)64321-3.pdf

The Molecular Pathology of Progressive Symmetric Erythrokeratoderma: A Frameshift Mutation in the Loricrin Gene and Perturbations in the Cornified Cell Envelope

We have performed retinal fluorescein angiography and audiometry in 32 familial and 7 sporadic cases of facioscapulohumeral muscular dystrophy. A mild to moderate retinal vasculopathy, consisting of retinal teleangiectasis and microaneursyms, was present in 18 of 37 evaluable angiograms (49%); 5 patients had minimal changes and 14 angiograms (38%) were normal. High frequency hearing loss was found in 25 (64%) out of 39 patients. Retinal changes were absent in 5 of 18 families (6 cases examined), and after correction for age and sex, hearing function was normal in 5 of 19 families (7 cases examined). Age and severity of the myopathy did not have a clear relationship with the retinal vasculopathy or the hearing loss. There were no differences between families in which the myopathy was linked to chromosome 4q35 and families in which linkage could not be proven. Minimal retinal vascular changes and high tone hearing loss can be observed occasionally in the normal population. Therefore, although retinal vasculopathy and hearing loss are part of the clinical picture of FSHD, these signs cannot be accepted as decisive criteria for FSHD in clinically equivocal cases.

On the significance of retinal vascular disease and hearing loss in facioscapulohumeral muscular dystrophy

Clinical data are presented from a survey of 41 families with dominantly inherited facioscapulohumeral muscular dystrophy (FSHD) in which over 500 family members were examined, including 168 affected subjects. New mutation could account for six isolated cases. Results suggest that 33% of heterozygotes over 40 years are mildly affected and a majority develop significant lower limb weakness; 19% over 40 years require wheelchairs. Presymptomatic testing of serum creatine kinase level (CK) is limited as a raised level occurs in only 80% of affected males under 40 years and 48% of affected women. Distribution of weakness, severity, age at onset, and CK varied between subjects, but provided no clinical evidence for genetic heterogeneity in a comparison between the 11 largest families. The conclusion of genetic homogeneity in FSHD, including subjects previously diagnosed as FSH type spinal muscular atrophy, is strongly supported by recent genetic linkage data.

https://jmg.bmj.com/content/jmedgenet/28/10/655.full.pdf

Genetic counselling in facioscapulohumeral muscular dystrophy.

Bilateral sloping high frequency hearing loss of 20–90 dB was found in six out of ten patients with infantile or adolescent onset FSHD. In all cases the basic defect could be traced to the cochlea. The outer hair cells of the basal turn are predominantly affected. In 20 patients with various other forms of muscular dystrophy or neuromuscular disorders with an FSH distribution, no sensorineural hearing loss was found. Myopathology of FSHD patients extended from mild to severe, often showing inflammatory infiltrates and type I fibre atrophy, without unequivocal differences between the two groups with and without hearing loss. It is concluded that cochlear dysfunction is a specific and frequenct phenomenon of early onset FSHD.

Hearing loss in facioscapulohumeral dystrophy

Progressive erythrokeratodermia and cochlear hearing impairment. A case report and review of the literature

In 8 healthy probands, 6 patients with functional voice disorders, 3 singers and 3 deaf patients we studied the regulation of the voice parameters amplitude and fundamental frequency at the beginning of phonation. Analyses were performed under the following conditions: (1) normal conditions; (2) after troubling pharyngeal and/or glottic mucosal receptors by topical anaesthesia; (3) in the case of normal hearing during disturbance of the audiophonatory feedback mechanism by binaural masking, and (4) with a combination of the latter two situations. The results are discussed.

Untersuchungen zur Regelung von Stimmschallparametern zu Beginn der Phonation

Evoked otoacoustic emissions (EOAE) remain intraindividually similar in repeated measurements. After application of medication for general anesthesia no significant changes of EOAE could be seen. Damping of amplitude and energy, mostly seen in the late phase of general anesthesia, might be caused by possible middle ear pressure changes from nitrous oxide. The recording of EOAE under general anesthesia provides an additional method in objective infant hearing evaluation and expands our diagnostic tools in those cases when children do not cooperate.

Messung evozierter otoakustischer Emissionen zu verschiedenen Zeitpunkten einer Intubationsnarkose

Wir berichten Uber otologische und audiologische Befunde sowie phoniatrische Ergebnisse bei 69 Kindern im Alter von 8 bis 10 Jahren, bei denen im 2. Lebensjahr wegen einer durchgehenden Lippen-Kiefer-Gaumenspalte (n = 41) oder einer isolierten Gaumenspalte (n = 28) der harte und der weiche Gaumen einzeitig operativ verschlossen wurden. Die Sprachentwicklung ist befriedigend, eine schwergradige Rhinophonia aperta wurde lediglich bei 8% der Patienten mit Lippen-Kiefer-Gaumenspalten beobachtet. Die hohe Zahl (etwa 50%) der auffAlligen Ohr- und HOrbefunde weist erneut auf die Notwendigkeit einer konsequenten, mOglichst im Spaltzentrum durchzufUhrenden pAdaudiologischen Kontrolle und Therapie hin. Als Folge des frUhen Verschlusses auch des harten Gaumens waren bei den Kindern mit Lippen-Kiefer-Gaumenspalten transversale OberkieferwachstumsstOrungen erkennbar, die jedoch kieferorthopAdisch auszugleichen sind. Insgesamt erscheint aus phoniatrisch-pAdaudiologischer Sicht die einzeitige Gaumenspaltenplastik im Alter von 2 Jahren empfehlenswert.

Antoinette Lamprecht

Papers

Hearing loss in facioscapulohumeral dystrophy

Progressive erythrokeratodermia and cochlear hearing impairment. A case report and review of the literature

Untersuchungen zur Regelung von Stimmschallparametern zu Beginn der Phonation

Messung evozierter otoakustischer Emissionen zu verschiedenen Zeitpunkten einer Intubationsnarkose

Pädaudiologisch-phoniatrische Ergebnisse bei 8- bis 10jährigen Patienten nach einzeitig operierten Gaumenspalten