麻豆传媒

What caused an infant with intrauterine growth restriction who was born at 31 weeks' gestation to present with mild erythema overlaid with a dry, parchment-like coating?

On examination, clinicians noted that the boy's "hairs were frizzy, coarse, and fragile, and his nails were normal," reported Laurence Garon, MD, of the Centre Hospitalier Universitaire Sainte-Justine in Montreal, and colleagues in .

His eyelids and mouth were not affected by ectropion or eclabium, respectively. He had low-set ears and blepharophimosis, characterized by wide-set eyes with under-developed eyelids, as well as three uncomplicated superficial hemangiomas. He also had osteopenia.

The team used polarized light microscopy to examine the patient's hair, which revealed alternating dark and light oblique bands in a distinct pattern known as tiger-tail banding.

These findings suggested a possible diagnosis of trichothiodystrophy (TTD), Garon and colleagues said. Genetic testing was performed, which confirmed the diagnosis. Specifically, the tests identified a heterozygous variant in the ERCC2 (XPD) gene.

Discussion

TTD -- which affects in the U.S. -- is an autosomal recessive genodermatosis characterized by dry and brittle hair; however, it can present with a wide range of additional systemic manifestations.

Genetic studies have shown that the ERCC2 (XPD) gene is the most common variant associated with TTD, but Garon and co-authors noted that " involving genes in the post-UV radiation DNA repair pathway have been identified."

Indeed, of at least 10 found to cause TTD, variants in one of three genes have been implicated in photosensitive forms of TTD, in which just a few minutes in the sun can cause a severe sunburn.

In addition to ERCC2, which was identified in this patient, other mutations include ERCC3 and GTF2H5; all of these produce proteins that work together as part of a group of proteins called the general transcription factor IIH (TFIIH) complex. Conversely, variants in the MPLKIP gene account for less than one in five of all cases of non-photosensitive TTD, and its proteins do not appear to be involved in DNA repair.

Signs of TTD may emerge prenatally, manifesting as maternal complications of pregnancy such as pre-eclampsia, HELPP (hemolysis, elevated liver enzymes, and low platelets) syndrome, and premature labor. Infants with TTD may be affected by intrauterine growth restriction; they "often have a low birth weight (<2,500 g) and are variably surrounded by a collodion membrane," the authors wrote.

Hair and nail abnormalities have been noted in all patients with TDD, according to a systematic review:

• Brittle hair (96%)
• Tiger-tail banding (73%)
• Nail anomalies (63%)
• Sulfur-deficient or cystine-deficient hair (71%)
• Sparse hair (48%)
• Alopecia (39%)

Skin is also affected in almost all patients with TTD, with ichthyosis of any type (65%) and photosensitivity (42%) observed most commonly, while eczema, ephelides, and erythroderma were relatively infrequent.

TTD usually has systemic, often neurologic effects, Garon and team wrote, "with most patients reporting some form of developmental delay or intellectual impairment."

TTD is also associated with microcephaly, ataxia, tremor, and seizures, the group noted. TTD usually results in growth deficiencies -- affected children tend to be of short stature and typically do not follow standard growth curves. The eyes are also affected in about 50% of children with TDD, most often presenting with abnormalities such as cataracts, nystagmus, and strabismus.

In the absence of any specific therapy for TTD, treatment should be multidisciplinary. "Pediatricians and special education professionals are needed to monitor the development and diagnose learning disabilities," Garon and colleagues wrote.

Ichthyosis should be treated on an as-needed basis with emollients, topical glucocorticoids, or topical tacrolimus, they added, and (Dupixent) has also been effective in one reported case.

"Sun protection is mandatory in UV-sensitive patients," they concluded.

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