Female infant with oncocytic cardiomyopathy and microphthalmia with linear skin defects (MLS): A clue to the pathogenesis of oncocytic cardiomyopathy?

Abstract

A infant girl had red stellate skin lesions on the cheeks and neck, and mildly short palpebral fissures. Her skin abnormality was typical of microphthalmia with linear skin defects (MLS), a newly recognized syndrome consisting of congenital linear skin defects and ocular abnormalities in females monosomic for Xp22. She died suddenly and unexpectedly at age 4 months; the cause of death was ascribed to oncocytic cardiomyopathy. Oncocytic cardiomyopathy occurs only in young children, who present with refractory arrhythmias leading to cardiac arrest. The coexistence of two rare conditions, one of which is mapped to the X chromosome, and an excess of affected females with oncocytic cardiomyopathy, make it likely that oncocytic cardiomyopathy is also X-linked, with Xp22 being a candidate region. Overlapping manifestations in the two conditions (ocular abnormalities in cases of oncocytic cardiomyopathy and arrhythmias in MLS) offer additional support for this hypothesis.

A very high density microsatellite map (1 STR / 41 kb) of 1.7 Mb on Xp22 spanning the microphthalmia with linear skin defects (MLS) syndrome critical region

“…1 The availability of biopsy specimens taken from the linear skin lesions of this patient provided a unique opportunity to investigate by PCR the minimal region of deletion causing the MLS phenotype. During this study, a second 'normal karyotype' patient presenting with the characteristic facial skin lesions was brought to our attention (Dr A David, personal communication, 1996) and was incorporated in the analysis.…”

Another observation of microphthalmia in an XX male: microphthalmia with linear skin defects syndrome without linear skin lesions

“…congenital heart defects, cardiomyopathy, and conduction disturbances) have been reported. These have included intermittent junctional rhythm and wandering atrial pacemaker with congenital heart defects (Lindor et al 1992), ventricular fibrillation with hypertrophic cardiomyopathy (Happel et al 1992), Morbitz II atrioventricular block (Naritomi et al 1992), oncocytic cardiomyopathy with congenital heart defect and Wolf-Parkinson-White syndrome (Bird et al 1994), and secundum atrial septal defect (Stratton et al 1998). Schaefer et al (1996) speculated that the deficiency of human holocytochrome c-type synthetase may be related to conduction disturbances in MLS syndrome.…”

“…The phenotypic variations are significant and some patients possess only one of the two major anomalies. To date, 22 affected individuals have been reported (Ropers et al 1982;Al-Gazali et al 1988;Donnenfeld et al 1990;Temple et al 1990;Allanson and Richter 1991;Gericke et al 1991;Thies et al 1991;Lindor et al 1992;Naritomi et al 1992;Happle et al 1993;Schaefer et al 1993;1996;Bird et al 1994;Eng et al 1994;Lindsay et al 1994;Mucke et al 1995;Stratton et al 1998).…”

“…Cytogenetic studies of MLS syndrome have revealed a variety of sexchromosome aberrations, including del Xp22 (-pter) in 11 female patients, translocation between the X and an autosomal chromosome in five female patients, X;Y translocation in four female patients, 46,XX in two female patients, of whom one did not undergo high-resolution analysis (Happle et al 1993) and the other with a normal karyotype who did (Bird et al 1994), as well as two XX male patients. Recent molecular investigations of Xp microdeletions in MLS syndrome have detailed the critical region of the genetic map 1996).…”

Microphthalmia with linear skin defects (MLS), Aicardi, and Goltz syndromes: are they related X-linked dominant male-lethal disorders?

“…Some patients have seizures, skeletal defects, and cardiac abnormalities (Bird et al, 1994). All known patients with MLS syndrome are females or 46,XX males (Stratton et al, 1998).…”