Background

This is a rare disorder affecting the hair of patients. Its name is derived from greek words and literally means hair with faulty sulfur nourishment.

OUTLINE

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/Immunohistochemistry/Electron Microscopy
Differential Diagnosis
Prognosis
Treatment
Commonly Used Terms
Internet Links

DISEASE ASSOCIATIONS	CHARACTERIZATION
	Adopted from: J Am Acad Dermatol 2001;44:891-920
Hair	Sparse or absent eyelashes, eyebrows Sparse or absent axillary, pubic, body hair Few vibrissae and otic hair
Nails	Dysplasia (onychodystrophy) Splitting (onychoschezia) Koilonychia Ridging Thickening (onychogryphosis) Yellow discoloration Unguis inflexus
Skin	Ichthyosis Follicular keratosis Collodion baby Erythroderma Photosensitivity (defective DNA repair) Erythema Eczema Hypohidrosis Pruritus Freckles Telangiectasia Hemangioma Lipoatrophy Parchment-like skin Poikiloderma Folliculitis Cheilitis Hyperpigmented eyelids Hypopigmented macules Pyoderma Palmar pustules
Nervous system	Mental retardation Autism Dysmyelinization Spasticity/paralysis Ataxia Cerebellar deficiency Intention tremor Motor control impaired Pyramidal signs Muscle tone diminished Peripheral neuropathy Hyperreflexia Absent deep tendon reflexes Hemiparesis Tetraparesis Intracranial calcifications Partial agenesis of corpus callosum Gray matter heterotopia and necrotizing encephalopathy Jerky eye movements Seizures Neurosensory hearing impairment Dysarthria Irritability Lethargy Perimedullary fibrosis of spinal cord
Dysmorphology and miscellaneous abnormalities	Growth retardation Cranial dysplasia Microdolichocephaly/microcephaly Protruding ears Hypoplastic ears Preauricular pits Cleft ear lobes Ear deformation not specified Thin-beaked nose Obstruction of the nose Receding chin Maxillary hypoplasia Dental abnormalities Caries Enamel hypoplasia Gastrointestinal malabsorption by jejunal atrophy White plaques on tongue Gingival hyperplasia Bifid uvula Small mouth Cleft lips Macrocheilia Raspy high-pitched voice Frontal bossing Facial hemiatrophy Trunk-limb disproportion Polythelia Short neck Goiter Excessive palmar crease Single palmar creases Progeria
Ocular	Cataract Conjunctivitis Nystagmus Photophobia Epicanthal folds Retinal dystrophy Entropion Ectropion Hypotelorism Exophthalmus/enophthalmus Esotropia Myopia Astigmatism Retrobulbar hemangioma Chorioretinal atrophy Retinal pigmentation Antimongoloid eye slant Tortuosity of retinal vessels Diminished red-green discrimination Strabismus Hypertelorism Bacterial keratitis Meibomian gland inflammation Blepharitis Pale optic disc Microcornea
Genital/urologic	Hypoplasia Cryptorchism Hypospadias Hydronephrosis Ureteral duplication Pyelocalyceal ectasia
Pulmonary	Pulmonary adenomatosis Asthma Bronchiectasis
Skeletal	Genu valgum Coxa valga Valgus deformity of the great toe Pes valgus Cubital and tibial valgus deformity Ulnar deviation of fingers Contracture Zygodactyly Clinodactyly Limited range of motion Pectus excavatum Scoliosis Thoracic kyphosis Lumbosacral lordosis Metacarpal bones of the thumb reduced in size
Cardiovascular	Hemangioma Telangiectasia Impairment of peripheral circulation Angioepitheliomas of the liver Pulmonic stenosis Ventricular septal defect
Immunologic/hematologic	Recurrent infections Neutropenia Anemia Hypereosinophilia Impaired NK cell activity

 

PATHOGENESIS

CHARACTERIZATION

Trichothiodystrophy: Update on the sulfur-deficient brittle hair syndromes Peter H. Itin, etal.

J Am Acad Dermatol 2001;44:891-920. Abstract quote Trichothiodystrophy (TTD) refers to a heterogeneous group of autosomal recessive disorders that share the distinctive features of short, brittle hair and an abnormally low sulfur content. Within the spectrum of the TTD syndromes are numerous interrelated neuroectodermal disorders. The TTD syndromes show defective synthesis of high-sulfur matrix proteins. Abnormalities in excision repair of ultraviolet (UV)-damaged DNA are recognized in about half of the patients. Three distinct autosomal recessive syndromes are associated with nucleotide excision repair (NER) defects: the photosensitive form of TTD, xeroderma pigmentosum, and Cockayne syndrome. The unifying feature of these conditions is exaggerated sensitivity to sunlight and UV radiation. In contrast to patients with xeroderma pigmentosum, no increase of skin cancers in patients with TTD has been observed. Genetically, 3 complementation groups have been characterized among photosensitive patients with TTD. Most patients exhibit mutations on the two alleles of the XPD gene. Rarely, mutated XPB gene or an unidentified TTD-A gene may result in TTD. In UV-sensitive TTD, the TFIIH transcription factor containing XPB and XPD helicase activities necessary for both transcription initiation and DNA repair is damaged. Beyond deficiency in the NER pathway, it is hypothesized that basal transcription may be altered leading to decreased transcription of specific genes. Depressed RNA synthesis may account for some clinical features, such as growth retardation, neurologic abnormalities, and brittle hair and nails. Therefore the attenuated expression of some proteins in differentiated cells is most likely explained by a mechanism distinct from DNA repair deficiency. The first transgenic mouse models for NER deficiencies have been generated. The TTD mouse as well as related cell models will provide important tools to understand the complex relationships between defects in DNA repair, low-sulfur hair shaft disorders, and the genotype-phenotype correlates for this constellation of inherited disorders, including the lack of predisposition to cancer in patients with TTD.

 

GROSS APPEARANCE/CLINICAL VARIANTS	CHARACTERIZATION
General
VARIANTS	Pediatr Dermatol 1998;15:31-4. Petrin JH, Meckler KA, Sybert VP. A new variant of tricho-thiodystrophy with recurrent infections, failure to thrive, and death.
A	Hair +/– nails
B (Sabinas)	Hair +/– nails + mental retardation
C (Pollitt)	Hair +/– nails + mental retardation + folliculitis + retarded bone age +/– caries
D (BIDS)	Brittle hair +/– nails + infertility + developmental delay + short stature
E (Tay + BIDS)	Ichthyosis + BIDS Hair +/– nails + mental retardation + short stature +/– decreased gonadal function +/– lenticular opacities/cataracts + failure to thrive/“progeria” + microcephaly +/– ataxia +/– calcifications of the basal ganglia + erythroderma and scale
F (PIBIDS)	Photosensitivity + IBIDS
G (Itin)	TTD with immune defects. Hair +/– mental retardation + chronic neutropenia or immunoglobulin deficiency
H	Trichothiodystrophy with severe intrauterine growth retardation (IUGR). Hair + severe IUGR and failure to thrive + developmental delay + recurrent infections + cataracts + hepatic angioendotheliomas

Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.

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Last Updated 6/4/2001

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