Characterization of tiger tail banding and hair shaft abnormalities in trichothiodystrophy

Abstract

Trichothiodystrophy (TTD) is a rare disorder characterized by short brittle hair with low cystine content and alternating dark and light (tiger tail) bands under polarizing microscopy. Some TTD patients show Ichthyosis, Brittle hair, Intellectual impairment, Decreased fertility, and Short stature (IBIDS). Others also have Photosensitivity (PIBIDS), or immune or neurological abnormalities including leukodystrophy. TTD patients are not predisposed to skin cancer. Xeroderma pigmentosum (XP) is markedly different, with lentiginous pigmentation and a 1000-fold increase of UV-induced skin cancers associated with defective DNA repair. Most PIBIDS patients have a mutation in an XP DNA repair gene (XPD or XPB). Rarely, TTD occurs in combination with XP. We studied hairs from 14 TTD and 4 XP-TTD patients for tiger tail banding and hair shaft abnormalities. Using a rotating microscope stage, all hairs in each sample showed tiger tail banding under polarized light. A variety of hair shaft abnormalities (trichoschisis, trichorrhexis nodosa-like defects, surface irregularities, ribbonning) was seen in TTD hairs using light or scanning electron microscopy and documented by digital photography. These varied in severity from patient to patient. The severity of hair shaft abnormalities was quantified by microscopic examination of 50 hairs from each patient. Amino acid analysis was performed on hair from 10 TTD and 2 XP-TTD patients. We observed an inverse relationship between hair sulfur (cystine) content and the percent of hairs with shaft abnormalities (Rval = 0.9) in keeping with the key role sulfur plays in hair toughness. Hairs that show tiger tail banding without shaft abnormalities have higher sulfur content than those with shaft abnormalities. There was no correlation between the presence of photosensitivity, or neurological or immune abnormalities and the percent of hairs with abnormalities among these patients. As controls, we examined hairs from 15 normals, 12 XP patients, 101 patients with various cornification disorders, 10 family members of XP or TTD patients, and 32 leukodystrophy patients. None of these hairs showed tiger tail banding, and 5 of 174 donors had weathering hair shaft abnormalities. Tiger tail banding, seen in all hairs on polarizing microscopy, and determination of the percent of hairs with certain shaft abnormalities, provides a reliable TTD diagnostic test and an estimation of the reduction in cystine content. Trichothiodystrophy (TTD) is a rare disorder characterized by short brittle hair with low cystine content and alternating dark and light (tiger tail) bands under polarizing microscopy. Some TTD patients show Ichthyosis, Brittle hair, Intellectual impairment, Decreased fertility, and Short stature (IBIDS). Others also have Photosensitivity (PIBIDS), or immune or neurological abnormalities including leukodystrophy. TTD patients are not predisposed to skin cancer. Xeroderma pigmentosum (XP) is markedly different, with lentiginous pigmentation and a 1000-fold increase of UV-induced skin cancers associated with defective DNA repair. Most PIBIDS patients have a mutation in an XP DNA repair gene (XPD or XPB). Rarely, TTD occurs in combination with XP. We studied hairs from 14 TTD and 4 XP-TTD patients for tiger tail banding and hair shaft abnormalities. Using a rotating microscope stage, all hairs in each sample showed tiger tail banding under polarized light. A variety of hair shaft abnormalities (trichoschisis, trichorrhexis nodosa-like defects, surface irregularities, ribbonning) was seen in TTD hairs using light or scanning electron microscopy and documented by digital photography. These varied in severity from patient to patient. The severity of hair shaft abnormalities was quantified by microscopic examination of 50 hairs from each patient. Amino acid analysis was performed on hair from 10 TTD and 2 XP-TTD patients. We observed an inverse relationship between hair sulfur (cystine) content and the percent of hairs with shaft abnormalities (Rval = 0.9) in keeping with the key role sulfur plays in hair toughness. Hairs that show tiger tail banding without shaft abnormalities have higher sulfur content than those with shaft abnormalities. There was no correlation between the presence of photosensitivity, or neurological or immune abnormalities and the percent of hairs with abnormalities among these patients. As controls, we examined hairs from 15 normals, 12 XP patients, 101 patients with various cornification disorders, 10 family members of XP or TTD patients, and 32 leukodystrophy patients. None of these hairs showed tiger tail banding, and 5 of 174 donors had weathering hair shaft abnormalities. Tiger tail banding, seen in all hairs on polarizing microscopy, and determination of the percent of hairs with certain shaft abnormalities, provides a reliable TTD diagnostic test and an estimation of the reduction in cystine content.