Incontinentia pigmenti‐associated ocular anomalies of paediatric incontinentia pigmenti patients in China

Song

Experimental Dermatology

et al. 2021

Incontinentia pigmenti (IP) is a rare X‐linked skin disease caused by mutations in the IKBKG gene, which is required for activation of the nuclear factor‐kappa B signalling pathway. Multiple systems can be affected with highly variable phenotypic expressivity. We aimed to clarify the clinical characteristics observed in molecularly confirmed Korean IP patients. The medical records of 25 females confirmed as IP by molecular genetic analysis were retrospectively reviewed. The phenotypic score of extracutaneous manifestations was calculated to assess the disease severity. The IKBKG gene partial deletion or intragenic mutations were investigated using long‐range PCR, multiplex ligation‐dependent probe amplification and direct sequencing methods. Among the 25 individuals, 18 (72%) were sporadic cases. All patients showed typical skin manifestations at birth or during the neonatal period. Extracutaneous findings were noted in 17 (68%) patients; ocular manifestations (28%), neurological abnormalities (28%), hair abnormalities (20%), dental anomalies (12%), nail dystrophy (8%). The common exon 4–10 IKBKG deletion was observed in 20 (80%) patients. In addition, five intragenic sequence variants were identified, including three novel variants. The phenotype scores were highly variable, ranging from abnormal skin pigmentation only to one or more extracutaneous features, although no significant difference was observed for each clinical characteristic between the group with sequence variants and that with common large deletion. Our cohort with IP showed heterogeneity of extracutaneous manifestations and high incidence of sporadic cases. Long‐term monitoring with multidisciplinary management is essential for evaluating the clinical status, providing adequate genetic counselling and understanding the genotype‐phenotype correlation in IP.

Section: Discussionsupporting

confidence: 91%

Importance of extracutaneous organ involvement in determining the clinical severity and prognosis of incontinentia pigmenti caused by mutations in the IKBKG gene

Song

Experimental Dermatology

et al. 2021

Journal of VitreoRetinal Diseases

“…Peng and colleagues 9 published the largest IP case series in the known literature of a sample of 61 children referred to Xin Hua Hospital in China. Forty-seven of their 61 patients (77%) demonstrated abnormal retinal findings—28 with bilateral disease and 19 with unilateral anomalies.…”

Section: Discussionmentioning

confidence: 99%

“…It is unknown whether the presence of neurological disease increases the incidence of more advanced retinal disease, but Chen et al had discovered a trend toward RD in their series of patients with neurologic disease. 8 Peng and colleagues 9 published the largest IP case series in the known literature of a sample of 61 children referred to Xin Hua Hospital in China. Forty-seven of their 61 patients (77%) demonstrated abnormal retinal findings-28 with bilateral disease and 19 with unilateral anomalies.…”

Section: Discussionmentioning

confidence: 99%

Retinal Manifestations of Incontinentia Pigmenti: A Case Series of 14 Patients Highlighting the Importance of Intravenous Fluorescein Angiography and the Benefits of Early Laser Photocoagulation

Bryan

Issa

Bakall

et al. 2020

Purpose: This case series describes the nature and frequency of retinal manifestations in patients with incontinentia pigmenti (IP). Methods: This is a retrospective single-center case series of all known patients with IP who presented to Associated Retina Consultants (Phoenix, AZ) between May 2016 and April 2019. Twenty-eight eyes of 14 patients with a dermatologic diagnosis of IP were included (n = 28). Most patients underwent examination under anesthesia with fundus photographs and intravenous fluorescein angiography (IVFA). Results: Of the 28 eyes, 8 (28.6%) had abnormal retinal findings on fundus examination. Of the 26 eyes that had IVFA, 10 (38.5%) had abnormal findings: Seven eyes (26.9%) had peripheral ischemia, 2 (7.7%) had previous peripheral laser scarring, and 2 (7.7%) had active peripheral neovascularization. Three eyes with normal examination results were found to have mild ischemia by IVFA. Patients with ischemia confirmed by IVFA were treated with laser photocoagulation. During follow-up, 4 previously treated eyes received additional laser photocoagulation. No patients showed vision loss, vitreous hemorrhage, retinal detachment, or adverse effects of treatment. No patients required vitreoretinal surgery. Conclusions: IP is a potentially blinding disease. Our case series demonstrates the efficacy of early treatment and the importance of ancillary testing with IVFA and fundus photography.

American J of Med Genetics Pt C

“…Surviving males with loss of function alleles occur as the result of three mechanisms: a 47, XXY karyotype (Buinauskaite, Buinauskiene, Kucinskiene, Strazdiene, & Valiukeviciene, 2010;Fowell, Greenwald, Prendiville, & Jampol, 1992;Kenwrick et al, 2001;Prendiville, Gorski, Stein, & Esterly, 1989), low-level germline and somatic mosaicism with recurrence risk to future female offspring (Fusco et al, 2017;Rashidghamat et al, 2016), and segmental forms secondary to postzygotic mosaicism of the IKBKG/NEMO gene mutation (Hull et al, 2015;Matsuzaki et al, 2018). Ocular manifestations occur in one-third of patients with IP and include an avascular peripheral retina which leads to peripheral ischemia, neovascular and fibrovascular proliferation (Holmstrom & Thoren, 2000;Peng et al, 2019;Rosenfeld & Smith, 1985). Additional associated findings include strabismus, cataracts, secondary glaucoma, optic atrophy, severe myopia, retinal pigmentary abnormalities, and microphthalmia (Ehrenreich, Tarlow, Godlewska-Janusz, & Schwartz, 2007;Fusco, Fimiani, Tadini, Michele, & Ursini, 2007;Meuwissen & Mancini, 2012;Mini c, Novotny, Trpinac, & Obradovi c, 2006;Scheuerle & Ursini, 1993.…”

Section: Incontinentia Pigmentimentioning

confidence: 99%

Systemic and ocular manifestations of a patient with mosaic ARID1A‐associated Coffin‐Siris syndrome and review of select mosaic conditions with ophthalmic manifestations

Utz

Brightman

Sandoval

et al. 2020

Mosaic genetic mutations may be somatic, germline, or "gonosomal" and have the potential to cause genetic syndromes, disorders, or malformations. Mutations can occur at any point in embryonic development and the timing determines the extent of distribution of the mutation throughout the body and different tissue types. The eye and visual pathway offer a unique opportunity to study somatic and gonosomal mosaic mutations as the eye consists of tissues derived from all three germ layers allowing disease pathology to be assessed with noninvasive imaging. In this review, we describe systemic and ocular manifestations in a child with mosaic Coffin-Siris syndrome. The patient presented with a significant medical history of accommodative esotropia and hyperopia, macrocephaly, polydactyly, global developmental delay, hypotonia, ureteropelvic junction (UPJ) obstruction, and brain MRI abnormalities. The ophthalmic findings in this patient were nonspecific, however, they are consistent with ocular manifestations reported in other patients with Coffin-Siris syndrome. We also review ophthalmic findings of select mosaic chromosomal and single-gene disorders. Ophthalmic assessment alongside clinical genetic testing may play an important role in diagnosis of genetic syndromes as well as understanding disease pathology, particularly when mosaicism plays a role.