Case Report A 3-year-old African-American boy presented for evaluation of failure to thrive, global developmental delay, and ichthyosis. [ajnr.org]

According to his parents’ description, infant presented with irregular hair loss after discharge. At 36 days of birth, he presented to hospital due to neonatal infectious pneumonia. [bmcpediatr.biomedcentral.com]

Hair, cilia, and nails were normal at this presentation. He presented two café-au-lait spots on his skin. Figure 1 A) Malar erythema with telangiectasia. B) Right eye retinography: A 0.9 × 0.9 cup-to-disc ratio is visible on the right eye. [scielo.br]

Case Presentation: Here, we report on an infant presenting with hypotonia, failure to thrive, microcephaly, dysmorphic features, brittle hair, hypertransaminasemia, and recurrent lower respiratory tract infections. [karger.com]

The documents contained in this web site are presented for information purposes only. The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment. [orpha.net]

• Nail Abnormality

  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. [orpha.net]

  abnormalities, dental abnormalities, and cryptorchidism. [ajnr.org]

  The nails may demonstrate koilynichia, a turning upward at the tips of the nails. Another term to describe this nail abnormality is ‘spooned’. It can be helpful to include the nails when moisturizing the skin of the hands and palms. [rarediseases.org]

• Fever

  The scalp hair is brittle and can be sparse; it breaks easily and, in some patients, will fall out during fever (febrile) illnesses. The hair may be ‘fine’ and feel soft or it may feel more course and dry. [rarediseases.org]

• Pneumonia

  At admission, chest X-ray showed infectious pneumonia. After 12 days treatment, due to unsatisfactory curative effect, thoracic spiral computed tomography reexamination was performed, showing multiple pneumonia episodes. [bmcpediatr.biomedcentral.com]

  During the neonatal and childhood period, there is substantial morbidity and mortality, with pneumonia and other infections (particularly sepsis) being the leading causes of death [1]. [dermnetnz.org]

  She had recurrent ear infections and pneumonias and died at the age of 9 years from acute infection following hip surgery.27 Figure 1 TTD and XP patients studied. (a) TTD patient TTD354BE at age 3 years. [nature.com]

  A significant number of TTD patients have abnormalities of the immune system and develop recurrent infections, including pneumonia and gastroenteritis. These infections can be difficult to manage leading to prolonged hospitalizations. [rarediseases.org]

• Failure to Thrive

  Case Presentation: Here, we report on an infant presenting with hypotonia, failure to thrive, microcephaly, dysmorphic features, brittle hair, hypertransaminasemia, and recurrent lower respiratory tract infections. [karger.com]

  Case Report A 3-year-old African-American boy presented for evaluation of failure to thrive, global developmental delay, and ichthyosis. [ajnr.org]

  The most severe form is characterized by very poor mental and motor performance and speech, failure to thrive and death during early childhood, most commonly due to (pulmonary) infections that account for an increased mortality rate in affected children [geneskin.org]

• Fracture

  In addition, the hair shafts appear ‘weathered’ having frayed ends and multiple fractures throughout the length of the shaft. The hair shafts easily break and some TTD patients rarely need haircuts. [rarediseases.org]

• Photosensitivity

  Trichothiodystrophy is classified into photosensitive and non-photosensitive sub-types [2]. Who gets trichothiodystrophy? The estimated incidence of trichothiodystrophy is one per million live births. Both sexes are affected equally. [dermnetnz.org]

  However, the observation that non-photosensitive TTD patients (who are NER-proficient) share with photosensitive cases all the clinical features except cutaneous photosensitivity indicates that the DNA repair defect may not be the main determinant of [geneskin.org]

  So-called photosensitive forms of TTD (with low level of in vitro UV-induced DNA repair, not constantly associated with marked clinical photosensitivity) are caused by mutations in genes encoding subunits of the transcription/repair factor IIH (TFIIH) [pubmed.ncbi.nlm.nih.gov]

  Mutations in at least one gene, MPLKIP, have been reported to cause a non-photosensitive form of trichothiodystrophy. Mutations in this gene account for fewer than 20 percent of all cases of non-photosensitive trichothiodystrophy. [medlineplus.gov]

  Etiology About half of the patients with TTD exhibit marked photosensitivity, due to abnormalities in excision repair of ultraviolet (UV)-damaged DNA. [orpha.net]

• Eczema

  Besides, infant presented with extensive eczema on the parietal region of his head skin (Fig. 1). At admission, chest X-ray showed infectious pneumonia. [bmcpediatr.biomedcentral.com]

  In a case report, efficacy of dupilumab (IL-4/IL-13 antibody) has been shown in a boy by significantly reducing the ichthyosis, eczema and pruritus.22 References 1. Takayama K, Danks DM, Salazar EP, Cleaver JE, Weber CA. [geneskin.org]

  Eczema occurs in a small percentage of patients and increases the problems with the pruritis. [rarediseases.org]

• Alopecia

  We report a 3-year-old boy with classic clinical features of TTD, including ichthyosis, alopecia, developmental delay, and tiger-tail banding of the hair shaft on polarizing microscopy. [ajnr.org]

  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. [orpha.net]

• Tremor

  In addition, TTD children can have tremors and difficulty coordinating fine and gross muscle coordination. A few patients have developed seizures. [rarediseases.org]

• Confusion

  We suggest a new clinico-genetic classification of TTD, which may help clinicians confused by the current acronyms used (IBIDS, PIBIDS...). [pubmed.ncbi.nlm.nih.gov]

• Neutropenia

  […] movements) approximately 50% of cases Rheumatological abnormalities including joint contractures and dislocations, axial osteosclerosis (abnormal hardening of bone), and distal osteopenia (bone weakening) Haematological abnormalities such as anaemia, neutropenia [dermnetnz.org]

  Less common are gonadal dysgenesis and abnormalities in the skeletal, cardiac, hepatic and hematologic (e.g. neutropenia) systems.9 Forty to 50% of patients show an abnormal sun reaction on minimal sun exposure with blistering and persistent erythema. [geneskin.org]

Management and treatment There is no specific treatment. The documents contained in this web site are presented for information purposes only. [orpha.net]

Successful treatment of trichothiodystrophy with dupilumab. 2021;46(7):1381-1383. [geneskin.org]

The peak of KLF9 mRNA induction ratio in normal cells after treatment was reached after about 6 h. However, the relative amount of KLF9 mRNA expression from cells with or without T3 treatment increased over time through 72 h. [nature.com]

During his 14 days of hospitalization, he was administrated with amoxicillin/sulbactam due to neonatal infectious pneumonia and other symptomatic treatments. [bmcpediatr.biomedcentral.com]

In the photosensitive TTD patients, the definition of the disease-gene and of the causative mutation(s) might be informative for the prognosis. [geneskin.org]

The prognosis is typically poor for children with severe disease and the median age of death is reported as 3 years. [dermnetnz.org]

Etiology About half of the patients with TTD exhibit marked photosensitivity, due to abnormalities in excision repair of ultraviolet (UV)-damaged DNA. [orpha.net]

No etiological diagnosis was determined at this point. The patient was initially medicated with topical timolol maleate and dorzolamide in both eyes. Latanoprost was further added, but IOP remained at 24 mmHg RE and 18 mmHg LE. [scielo.br]

Ichthyosis: etiology, diagnosis, and management. Am J Clin Dermatol 2003;4(2):81-95. Itin PH, Sarasin A, Pittelkow MR. Trichothiodystrophy: update on the sulfur-deficient brittle hair syndromes. [rarediseases.org]

Summary 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. [orpha.net]

We hope to be able to correlate these laboratory abnormalities with the clinical features to better understand the mechanism of cancer prevention by DNA repair. Patients will be offered counseling and education for cancer control.... [clinicaltrials.gov]

[…] gastrostomy tube placement for prevention of malnutrition, treatment of spasticity, management of hearing loss, cataracts, and other ophthalmologic complications and dental care to minimize dental caries. [geneskin.org]

Article CAS PubMed Google Scholar Kraemer KH, DiGiovanna JJ, Moshell AN, Tarone RE, Peck GL : Prevention of skin cancer in xeroderma pigmentosum with the use of oral isotretinoin. N Engl J Med 1988; 318: 1633–1637. [nature.com]

XPD mutations prevent TFIIH-dependent transactivation by nuclear receptors and phosphorylation of RARalpha. Cell 2002; 109:125–35. CrossRef PubMed CAS Google Scholar Liu J, He L, Collins I et al. [link.springer.com]

For the TTD patients who are photosensitive, UV protection is important to prevent severe burns. Patients should avoid being outside for prolonged periods without protection. [rarediseases.org]