Trichothiodystrophy Presenting with Cardiomyopathy and Recurrent Stroke Episodes

Background: The term trichothiodystrophy (TTD) (OMIM 601675) refers to a rare genetic syndrome, presenting with a heterogeneous clinical picture and variable prognosis. Main symptoms include a typical brittle hair texture, variable photosensitivity, xerosis cutis, short stature, and psychomotor retardation. In autosomal recessive forms, mutations in XPB, XPD, TTDA, and TTDN1 genes are described.

Case Report: Here, we report on a 3-year-old boy, who presented with acute onset of left hemiparesis with facial nerve palsy. In the past, developmental delay and dilated cardiomyopathy of unknown origin were diagnosed. He was pretreated with anticongestive drugs. Brain magnetic resonance imaging (MRI) showed acute ischemic infarction of the right middle cerebral artery. Intravenous thrombolysis within 3 hours after onset of symptoms led to recanalization and dramatic improvement in symptoms. In the following, low-dose aspirin treatment (2 mg/kg/d) was started for further stroke prevention. However, on day 7, he suffered from a prolonged focal epileptic seizure with altered consciousness. MRI was repeated and showed a filling defect in the left middle cerebral artery. On the basis of the successful lysis during the initial episode and after careful evaluation of contraindications, intravenous thrombolysis was administered again. However, in this situation, he did not show any benefit. Moreover, on day 8, he even suffered from reinfarction of his right middle cerebral artery and additional infarction of his left posterior cerebral artery. Treatment was continued with low-molecular heparin and later switched to warfarin. Unfortunately, the subsequent neurological outcome was unfavorable. There was no evidence of causal thrombophilia, dyslipidemia, sickle cell disease, metabolic, or autoimmune disorder. Echocardiography showed a dilated left ventricle and a significantly reduced- shortening fraction, while no thrombi could be detected. However, due to the infarct morphology (cardio-) embolic infarction was considered as probable underlying cause. Since birth, he had suffered from dry, scaly skin, and had a striking hair texture with brittle, short hair with patchy thinning and alopecic areas, suggesting TTD as the underlying disease. With electron and polarization microscopy of the hair, the diagnosis TTD could be confirmed. The hair abnormalities result from sulfur deficiency in hair matrix proteins. Seven months after the acute episode, the boy died due to cardiac insufficiency after severe status epilepticus.

Conclusion: This is the second documented case showing a possible association of TTD with dilated cardiomyopathy and strokes.¹ Cardiovascular events may at least in parts account for the high mortality in patients affected with this disease. In summary, uncommon hair structure in combination with cardiomyopathy and stroke should lead to an investigation of TTD.

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References

1 Toelle SP, Valsangiacomo E, Boltshauser E. Trichothiodystrophy with severe cardiac and neurological involvement in two sisters. Eur J Pediatr 2001;160(12):728–731.