Inherited syndrome with mild psychomotor retardation, hypogonadism, short stature, and brittle hair.
Trichothiodystrophy (TTD); Amish Brittle Hair Syndrome; Hair-Brain Syndrome; BIDS Syndrome (Brittle Hair and Nails, Intellectual Deficit, Decreased Fertility, Short Stature Syndrome); PIBIDS (Photosensitivity, Ichthyosis, Brittle Hair and Nails, Intellectual Deficit, Decreased Fertility, Short Stature Syndrome); IBIDS (Ichthyosis, Brittle Hair and Nails, Intellectual Deficit, Decreased Fertility, Short Stature Syndrome); Pollitt Syndrome.
Initially described in 25 members of an Amish kindred. To date, more than 100 cases have been reported and the estimated incidence is in the range of 1:1,000,000 live births. Both genders are equally affected.
Autosomal recessive transmission. TTD results from mutations in one of several different DNA repair genes (XPB, XPD, or TTDA) and TTDN1, a gene whose function remains poorly defined.
Brittle hair affects all TTD patients, which in the majority of cases is due to markedly reduced cystine content resulting in a lack of sulfur-rich matrix proteins. Almost half of the patients also have sparse hair and alopecia. Electron- and lightmicroscopy examination of the hair show multiple shaft abnormalities with an irregular and grooved surface, transverse fractures (trichoschisis) and occasionally trichorrhexis nodosa or 180° twists similar to pili torti. Polarizing microscopy reveals a diagnostic pattern of alternating light and dark banding, which, due to its appearance, has been called “tiger tail banding” or “zig-zag” pattern. The same underlying defect seems to be responsible for onychodystrophy (brittle, dysplastic, dystrophic nails, with yellowish discoloration). A wide spectrum of other clinical manifestations include intellectual impairment (presenting as failing to achieve developmental milestones, such as sitting, talking, walking) in over 80% of patients, short stature (in 73%) and decreased fertility (in 14%) secondary to gonadal dysgenesis/hypogonadism. The most common skeletal findings are osteosclerosis (in 14%), delayed bone age (in 13%), and osteopenia (in 9%). Joint contractures and dislocations are rare. For unknown reasons, the height and weight in most patients tend to drop off the growth curve as they get older. A minority of patients shows dysmyelination (in 14%), cerebellar atrophy, and dilated ventricles (each in 4%) on neuroimaging scans. Ophthalmologic findings include microcornea (in 44%), microphthalmia (in 8%), cataracts (in 28%), nystagmus (14%), strabismus (10%), and xerophthalmia. Characteristic facial features such as microcephaly (in 50% of patients), micrognathia (in 29%), and prominent ears have been described. Cardiac anomalies are reported in less than 10% of patients and include cardiomyopathy, pulmonary valve stenosis, and ventricular septal defect. Anemia is reported in 12% of patients. About one-third of newborns with TTD are small for gestational age. Short stature and failure to thrive affects more than 70% of cases. TTD has a 20-fold increased incidence of death ...