Trichothiodystrophy

Trichothiodystrophy or TTD is a heterogeneous group disorders characterized by short, brittle hair with low-sulphur content (due to an abnormal synthesis of the sulphur containing keratins).

Epidemiology

The exact prevalence of TTD is unknown, but it appears to be rather uncommon.

Clinical description

Within the spectrum of the TTD syndromes are numerous syndromes affecting mainly organs derived from the neuroectoderm. The clinical appearance is always characterized by brittle and fragile hair, often combined with growth retardation and intellectual deficit, congenital ichthyosis and nail abnormalities, among other symptoms. The abnormalities are usually obvious at birth, with variable clinical expression. The variants of TTD, depending on their different associations, are: BIDS syndrome (or TTD type D or Amish Brittle Hair syndrome), IBIDS syndrome (or Tay syndrome or TTD typeE), PIBIDS syndrome (or TTD type F), Sabinas syndrome (TTD type B), SIBIDS syndrome, ONMRS (Itin syndrome) and Pollitt syndrome (TTD type C).

Etiology

About half of the patients with TTD exhibit marked photosensitivity, due to abnormalities in excision repair of ultraviolet (UV)-damaged DNA. In most cases, the deficiency in DNA excision repair is indistinguishable from that observed in Xeroderma Pigmentosum type D. In this photosensitive group of patients, the majority of cases (95% of patients) are due to mutations within the XPD (ERCC2) gene (localized to 19q13.2-q13.3). The remaining cases are caused by mutations within the XPB gene. These genes encode the DNA-dependent ATPase/helicase subunits of TFIIH (transcription factor). So far, no gene has been isolated for the nonphotosensitive group.

Diagnostic methods

The diagnostic findings of TTD are short, unruly, brittle hair, with alternating dark and light bands under polarizing microscopy (tiger-tail pattern), trichoschisis (or trichorrhexis), and an absent or defective cuticle visualized by scanning electron microscopy.

Differential diagnosis

TTD is a differential diagnosis in congenital alopecias.

Antenatal diagnosis

Prenatal diagnosis, based on measurement of DNA repair in trophoblasts or amniotic cells, is available.

Genetic counseling

TTD is an autosomal recessive disorder.

Management and treatment

There is no specific treatment.