Transpupillary thermotherapy (TTT) for age-related macular degeneration

Purpose. To review the results of transpupillary thermotherapy (TTT) on choroidal neovascular membranes associated with age-related macular degeneration (AMD). Materials and Methods. 35 eyes of 35 patients with AMD and choroidal neovascularization and exudation were treated with TTT and had fundus photographs and fluorescein angiography (FA) before and at least six months after TTT. 28 eyes had predominantly occult lesions as seen on FA, while 7 demonstrated primarily classic lesions. All were treated with 650 mw power or less using the 810 nm diode laser (3000 micron spot, duration of 60 seconds). Visual acuity, lesion size, and amount of subretinal fluid were determined by results of examination and review of photographs and fluorescein angiograms. Results. A 50% reduction in subretinal fluid was achieved in 67% of treated eyes overall, with stabilization of vision (less than three lines of visual acuity lost) in 86%. Complications from treatment were infrequent (9%) and involved hemorrhage noted in the region of treatment upon follow-up. Conclusion. TTT promotes resolution of subretinal fluid and appears to stabilize visual acuity in patients with exudative AMD.     

NEMO mutation as a cause of familial occurrence of Behçet's disease in female patients

Takada H, Nomura A, Ishimura M, Ichiyama M, Ohga S, Hara T. NEMO mutation as a cause of familial occurrence of Behçet's disease in female patients. Behçet's disease is a chronic, relapsing, multisystem inflammatory disease of unknown etiology. Nuclear factor κB (NF‐κB) essential modulator (NEMO) that is required for the activation of NF‐κB plays an important role in inflammation. To investigate the role of NEMO in the pathogenesis of Behçet's disease, we analyzed NEMO gene and its expression pattern in tissues in a family with Behçet's disease. We found a heterozygous mutation (1217A> T, D406V) in a 6‐year‐old girl and her mother. Skewed X‐chromosome inactivation was not observed in the peripheral blood mononuclear cells as well as in oral and intestinal mucosa of the patients. Accordingly, there was a significant proportion of peripheral blood monocytes that did not produce sufficient intracellular tumor necrosis factor‐α with the stimulation of lipopolysaccharide. Heterozygous NEMO mutation is a cause of familial occurrence of Behçet's disease in female patients.     

Incontinentia pigmenti or Bloch-Sulzberger syndrome: a rare X-linked genodermatosis

Incontinentia pigmenti is a rare X-linked genodermatosis that affects mainlyfemale neonates. The first manifestation occurs in the early neonatal period andprogresses through four stages: vesicular, verruciform, hyperpigmented andhypopigmented. Clinical features also manifest themselves through changes in theteeth, eyes, hair, central nervous system, bone structures, skeletal musculatureand immune system. The authors report the case of a patient with cutaneouslesions and histological findings that are compatible with the vesicular stage,emphasizing the importance of early diagnosis and appropriate therapeuticmanagement.     

Resolving clinical diagnoses for syndromic cleft lip and/or palate phenotypes using whole‐exome sequencing

Individuals from three families ascertained in Bogota, Colombia, showing syndromic phenotypes, including cleft lip and/or palate, were exome‐sequenced. In each case, sequencing revealed the underlying causal variation confirming or establishing diagnoses. The findings include very rare and novel variants providing insights into genotype and phenotype relationships. These include the molecular diagnosis of an individual with Nager syndrome and a family exhibiting an atypical incontinentia pigmenti phenotype with a missense mutation in IKBKG. IKBKG mutations are typically associated with preterm male death, but this variant is associated with survival for 8–15 days. The third family exhibits unusual phenotypic features and the proband received a provisional diagnosis of Pierre Robin sequence (PRS). Affected individuals share a novel deleterious mutation in IRF6. Mutations in IRF6 cause Van der Woude and popliteal pterygium syndrome and contribute to nonsyndromic cleft lip phenotypes but have not previously been associated with a PRS phenotype. Exome sequencing followed by in silico screening to identify candidate causal variant(s), and functional assay in some cases offers a powerful route to establishing molecular diagnoses. This approach is invaluable for conditions showing phenotypic and/or genetic heterogeneity including cleft lip and/or palate phenotypes where many underlying causal genes have not been identified.     

A successful treatment of tadalafil in incontinentia pigmenti with pulmonary hypertension

We describe a female infant with incontinentia pigmenti complicated by severe pulmonary arterial hypertension that was markedly improved by tadalafil administration. The infant was referred to our institution because of neonatal seizures and generalized skin rash at the age of 1 day. She was diagnosed with incontinentia pigmenti on skin biopsy findings. In addition to incontinentia pigmenti, she had pulmonary arterial hypertension without structural heart disease. The pulmonary hypertension rapidly worsened at the age of 2 months and was confirmed by cardiac catheterization. The pulmonary artery pressure was equal to systemic pressure but it decreased in response to nitric oxide inhalation. We, therefore, initiated treatment with tadalafil of 1 mg/kg/day. The follow-up cardiac catheterization performed at 9 months revealed dramatic improvement in the pulmonary artery pressure. An IKBKG mutation with deletion of exons 4–10 was detected in the blood of both the patient and her mother. Our experience indicates that tadalafil may be beneficial in treating pulmonary arterial hypertension associated with incontinentia pigmenti.     

7例新生儿皮肤异常的临床特征及遗传分析

目的 分析新生儿期色素失禁症(IP)患儿的临床表型及遗传学特征。方法 回顾性分析2019年6月至2021年6月安徽省儿童医院7例IP的临床资料;利用gap-PCR及Sanger测序,对患儿IKBKG基因进行外显子缺失和点突变筛查,对结果阴性患儿续以外显子组测序(WES)检测。结果 7例中有5例经基因检测确诊为IKBKG变异导致的IP,其中p.Q120*和p.K277Nfs*4为未报导过的新变异。1例经WES检测考虑PLEC变异所致大疱性表皮松解症,1例因拒绝进一步WES检测结果诊断不明。结论 IKBKG基因靶向gap-PCR及Sanger测序是确诊IP的有效一线检测;新鉴定的2个致病性变异扩展了IKBKG致病性变异谱。     

A genetic cause for neonatal encephalopathy: incontinentia pigmenti with NEMO mutation

Incontinentia pigmenti (IP) is not generally recognized as a cause of neonatal encephalopathy. A full-term infant developed a rash and encephalopathy with lesions in the basal ganglia and periventricular white matter 3 days after a normal delivery. Typical skin changes of IP were confirmed by histology and mutation analysis of the NFkappaB essential modulator (NEMO) gene. CONCLUSION: The mechanism of brain injury appears to be increased apoptosis after inflammation and this condition should be included in differential diagnosis of neonatal encephalopathy if skin lesions are present.     

皮肤色素失禁症合并双眼视网膜病变1例

患儿女,1岁7个月。患儿四肢、躯干泛发性皮疹1年3个月。患儿出生即全身皮肤干燥;3个月时,躯干、四肢曾起过水疱;1岁时,出现疣状丘疹和斑片,呈涡轮状排列;4个月前,患儿因"视物不见1个月"到本院眼科就诊,诊断为"双眼视网膜病变"。1个月前,来本院皮肤科门诊就诊,诊断为皮肤色素失禁症合并双眼视网膜病变。目前仍在随访中。