Trichothiodystrophy: Ultrastructural Studies of Two Patients

Abstract

An 18-month-old and an 8-year-old girl had trichothiodystrophy (TTD). Microscopic observation of the hair under polarized light showed typical alternation of bright and dark bands; amino acid analysis of the hair demonstrated a marked reduction of cystine levels. Both patients had skin lesions consisting in the older child of diffuse follicular keratosis since birth, and in the younger of an ichthyosiform dermatitis on the lower legs that appeared at age 4 months. Ultrastructural studies of the skin showed striking similarities in both cases: perinuclear vacuoles with a unit membrane in the keratinocytes, and dispersed, irregularly arranged bundles of tonofilaments particularly at the desmosome junction. The origin of the vacuoles is unknown; the abnormalities of the tonofilaments could be explained on the basis of a generalized abnormality in sulfur-containing proteins, reflecting a disturbance in the synthesis of keratins. These electron microscopy findings could be considered as a peculiar feature of ichthyotic skin in patients with TTD.

Trichothiodystrophy: a systematic review of 112 published cases characterises a wide spectrum of clinical manifestations

“…All except one47 of these 46 patients also had neurologic abnormalities. Radiographic bone abnormalities were reported in 38% patients.…”

“…The most common tooth abnormality was caries (19%). Eleven of these 21 patients had severe caries 13 17 22 47 57 58 69 72 76 77 99…”

Diseases of cutaneous appendages

“…551 This causes splitting and breaking of the hairs and discrete patches of alopecia. 542,543 It has been suggested, and confirmed in mutant (TTD) mice, that the neurological features seen in some of these related syndromes are due to thyroid hormone deficiency resulting from XPD mutations. 542,543 It has been suggested, and confirmed in mutant (TTD) mice, that the neurological features seen in some of these related syndromes are due to thyroid hormone deficiency resulting from XPD mutations.…”

What’s new in trichothiodystrophy

“…Crovato and Rebora underlined that if ichthyosis developed in late infancy patients are affected by IBIDS, and if congenital ichthyosis is present Tay syndrome must be considered 14 . Ultrastructural studies of the ichthyotic skin showed that the reduction and irregularly arranged bundles of tonofilaments probably mean a generalized anomaly in high sulphur content protein, reflecting a synthesis abnormality of the sulphur containing keratins 15 …”

“…A more detailed examination reveals that their intelligence is impaired. Some studies showed decreased IQ in patients with TTD and PIBI(D)S 9–21 . Mental retardation and delayed or arrested physical maturation occur frequently in these patients 22 .…”