Trichothiodystrophy in Adult
- Brittle hair
- Intellectual impairment with low IQ
- Decreased fertility
- Short stature
Approximately half of TTD patients experience photosensitivity due to a defective nucleotide excision repair. Mutations in ERCC2, ERCC3, and GTF2H5 genes producing XPB, XPD, and p8/TTDA subunits of the general transcription factor IIH (TFIIH) are responsible for photosensitive TTD. The ineffective DNA repair likely leads to photosensitivity. Although less frequent, non-photosensitive TTD patients have been shown to have mutations in TTDN1 or MPLKIP, genes of unknown function.
Dry, scaly, and/or thickened skin was reported in 65% of patients (out of 112 in a review).
Short, brittle hair due to sulfur deficiency is a diagnostic characteristic of TTD. It results in "tiger tail" banding in the hair – alternating light and dark bands seen under polarizing light. Hair may be sparse and alopecia may be seen.
Most patients have a form of intellectual impairment, such as failure to reach developmental milestones and low IQ. Microcephaly, abnormal gait, and increased tendon reflexes have also been reported. On neuroimaging, some TTD patients demonstrated impaired development of the brain with features such as demyelination and cerebellar atrophy.
Up to 14% of patients experienced sexual / reproductive abnormalities, primarily hypogonadism. Fertility is decreased. Of those who achieved gestation, approximately half experienced pregnancy complications, such as preeclampsia, and around 50% of the infants had abnormal birth characteristics, such as low birth weight, premature birth, collodion membrane, and congenital cataracts, usually indicating TTD inheritance in the baby.
Short stature and facial abnormalities
TTD patients generally have a short stature and an unusual facial appearance, including a beaked nose, protruding ears, and a receding chin.
Additional systemic features observed
- Recurring infections, predominantly respiratory, contributing to increased neonatal and childhood morbidity and mortality
- Ocular abnormalities, primarily cataracts at all ages
- Seizure disorder, primarily in patients with a mutated TTDN1 gene
- Dental abnormalities and caries
- Cardiac and hepatic abnormalities
Q84.1 – Congenital morphological disturbances of hair, not elsewhere classified
723551003 – Trichothiodystrophy
- Trichorrhexis nodosa – The most common structural hair abnormality. With dermatoscope, weakened portions of the hair shaft with fraying causing breakage of the hair are observed.
- Pili annulati – An autosomal dominant disorder presenting with striped, light and dark patterning with dermatoscope. Not all hair is affected. Patients do not present with concomitant symptoms.
- Menkes disease – X-linked disorder associated with defective copper transport resulting in sparsely distributed, short, fragile hair with a wool-like quality. Pilli torti, flattened and twisted hairs, are seen under dermatoscope.
- Monilethrix – An autosomal dominant condition causing short, brittle hair due to defective keratin genes. Under dermatoscope, elliptical nodes are present on the hair shaft, resulting in a beaded appearance.
- Trichorrhexis invaginata – Intussusception within the hair shaft results in a ball and socket deformity causing short, sparse hair seen under dermatoscope. This is a finding in Netherton syndrome, which also has ichthyosis as a characteristic.
Xeroderma pigmentosum (XP) can resemble TTD due to photosensitivity and neurologic impairment. Both disorders are caused by mutations in DNA repair genes. XP lacks the brittle, sulfur-deficient hair characteristic of TTD.
Cockayne syndrome can resemble TTD due to similar features such as prominent ears, short stature, ocular abnormalities, and immature sexual development. Although Cockayne patients are sun sensitive, they are not as affected as photosensitive TTD patients. The differentiating factor in Cockayne is the normal presentation at birth and subsequent postnatal failure of brain growth. Cockayne syndrome does not present with brittle hair.