Novel SETBP1 D874V adjacent to the degron causes canonical schinzel-giedion syndrome: a case report and review of the literature.

Schinzel-Giedion syndrome (SGS) is a severe multisystem disorder characterized by distinctive facial features, profound intellectual disability, refractory epilepsy, cortical visual impairment, hearing loss, and various congenital anomalies. SGS is attributed to gain-of-function (GoF) variants in the SETBP1 gene, with reported variants causing canonical SGS located within a 12 bp hotspot region encoding SETBP1 residues aa868-871 (degron). Here, we describe a case of typical SGS caused by a novel heterozygous missense variant, D874V, adjacent to the degron. The female patient was diagnosed in the neonatal period and presented with characteristic facial phenotype (midface retraction, prominent forehead, and low-set ears), bilateral symmetrical talipes equinovarus, overlapping toes, and severe bilateral hydronephrosis accompanied by congenital heart disease, consistent with canonical SGS. This is the first report of a typical SGS caused by a, SETBP1 non-degron missense variant. This case expands the genetic spectrum of SGS and provides new insights into genotype-phenotype correlations.

Effect of the Intralesional Forms of Methylprednisolone Acetate and Methotrexate on Psoriatic Nails.

Individuals with psoriatic nails often have a lower quality of life relative to their counterparts with healthy nails. Methotrexate (MTX), an anti-neoplastic agent, is a longstanding treatment option for nail psoriasis. In the current study, we compared the effects of MTX to that of a corticosteroid, namely, methylprednisolone acetate (i.e., Depo-Medrol®) across individuals with nail psoriasis. We used a cohort study design, and both agents were administered intralesionally. Outcome variables were based on the Nail Psoriasis Severity Index (NAPSI). We quantified the effect in terms of change in NAPSI, complete cure at week 16, and cure between 32 and 36 weeks. Our regressions demonstrated that reduced NAPSI scores with Depo-Medrol were, on average, greater than that with MTX by 2.27 (n = 48, P = 0.000255) at week 16. Similarly, the odds of complete cure at week 16 was greater with Depo-Medrol® than with MTX (odds ratio = 18.6, P < 0.0001). In terms of both complete cure and change in NAPSI, Depo-Medrol® was significantly more effective than MTX at a follow-up period of 32-36 weeks. Our study established that intralesional Depo-Medrol® is more effective than intralesional methotrexate for treating nail psoriasis.

An Atlas of the Human Nail.

Dermatologic literature describes nail abnormalities involving nail bed as linear erythronychia or onychomatricoma. The abnormality reflects cognitive content of the nail bed. A resourceful epidermis capable of manifesting in a variety of clinical appearances depends on initiating stimulus affecting remarkably its nail bed matrix cells. These cells are stem cells (NBMSC) migrating distally to cover remarkably the underlying nail bed dermal ridges that are homologous to finger print dermal ridges. Normally, adult nail bed epidermal cells are uniform and keratinize with the stratum corneum without a granular layer.

Onychocytic Matricoma: A Clinical, Dermoscopic, and Pathological Analysis of 14 Cases.

ABSTRACT: Onychocytic matricoma (OCM) is a benign neoplasm of the nail matrix. Only 18 cases of this tumor have been reported in the literature to date. We retrospectively analyzed the clinical features of 14 patients with OCM. The most common clinical feature was longitudinal xanthopachyonychia (n = 9), followed by longitudinal leukopachyonychia (=3) and longitudinal pachymelanonychia (n = 2). The most common clinical findings identified following dermoscopy and analysis at high magnification of classical photographs were free-edge thickening of the nail plate without pitting (n = 14), longitudinal ridging (n = 7), round white clods (n = 7), white dots (n = 7), and filiform hemorrhages (n = 7), followed by oval and linear white clods (n = 5), fuzzy lateral border (n = 5), and red-purple blood clods (n = 3). Nail clipping histopathology showed a thickened nail plate with multiple, small, round-to-oval spaces. The tumor expressed immunopositivity for LEF-1. Dermoscopy of the nail plate and nail clipping histology provides useful information with regards to the differential diagnosis with subungual squamous cell carcinoma and nail melanoma. Ex vivo-in vivo correlation facilitates a better dermoscopic assessment of this unique underrecognized disease. However, the differential diagnosis between OCM and onychocytic carcinoma requires biopsy of the tumor. LEF-1 as an onychogenic marker can be used to resolve the differential diagnosis between OCM and subungual longitudinal acanthoma/seborrheic keratosis.

Establishment and characterization of ZJUCHi003: an induced pluripotent stem cell line from a patient with Temple-Baraitser/Zimmermann-Laband syndrome carrying KCNH1 c.1070G > A (p.R357Q) variant.

Pathogenic variants of the KCNH1 gene can cause dominant-inherited Temple-Baraitser/Zimmermann-Laband syndrome with severe mental retardation, seizure, gingival hyperplasia and nail hypoplasia. This study established an induced pluripotent stem cell (iPSC) line using urinary cells from a girl with KCNH1 recurrent/hotspot pathogenic variant c.1070G > A (p.R357Q). The cell identity, pluripotency, karyotypic integrity, absence of reprogramming virus and mycoplasma contamination, and differential potential to three germ layers of the iPSC line, named as ZJUCHi003, were characterized and confirmed. Furthermore, ZJUCHi003-derived neurons manifested slower action potential repolarization process and wider action potential half-width than the normal neurons. This cell line will be useful for investigating the pathogenic mechanisms of KCNH1 variants-associated symptoms, as well as for evaluating novel therapeutic approaches.

Ophthalmic Manifestations of Heimler Syndrome in Two Siblings With PEX1 Variants.

PURPOSE: To report two new cases with confirmed diagnosis of Heimler syndrome and describe their systemic and ophthalmic phenotype and visual rehabilitation. METHODS: Retrospective review of medical records. RESULTS: Both siblings were diagnosed as having sensori-neural hearing loss and retinal dystrophy with exuberant intraretinal cystoid spaces and cone-rod dysfunction. The older sibling also had amelogenesis imperfecta and neither had nail abnormalities. Genetic analysis identified homozygosity for the pathogenic variant c.2528G>A p.(Gly843Asp) in the PEX1 gene in both siblings. The parents were heterozygous carriers of the variant. CONCLUSIONS: The authors report a familial case of Heimler syndrome due to biallelic PEX1 pathogenic variants that manifested as macular dystrophy characterized by cone-rod dysfunction and complicated by intraretinal cystoid spaces. Review of the literature shows that ocular phenotype is variable in patients with Heimler syndrome. [J Pediatr Ophthalmol Strabismus. 2024;61(1):59-66.].

Absent meibomian glands and cone dystrophy in ADULT syndrome: identification by whole exome sequencing of pathogenic variants in two causal genes TP63 and CNGB3.

BACKGROUND: Ectrodactyly is a rare congenital limb malformation characterized by a deep median cleft of the hand and/or foot due to the absence of central rays. It could be isolated or depicts a part of diverse syndromic forms. Heterozygous pathogenic variants in the TP63 gene are responsible for at least four rare syndromic human disorders associated with ectrodactyly. Among them, ADULT (Acro-Dermato-Ungual-Lacrimal-Tooth) syndrome is characterized by ectodermal dysplasia, excessive freckling, nail dysplasia, and lacrimal duct obstruction, in addition to ectrodactyly and/or syndactyly. Ophthalmic findings are very common in TP63-related disorders, consisting mainly of lacrimal duct hypoplasia. Absent meibomian glands have also been well documented in EEC3 (Ectrodactyly Ectodermal dysplasia Cleft lip/palate) syndrome but not in ADULT syndrome. METHODS: We report a case of syndromic ectrodactyly consistent with ADULT syndrome, with an additional ophthalmic manifestation of agenesis of meibomian glands. The proband, as well as her elder sister, presented with congenital cone dystrophy.The molecular investigation was performed in the proband using Whole Exome Sequencing. Family segregation of the identified variants was confirmed by Sanger sequencing. RESULTS: Two clinically relevant variants were found in the proband: the novel de novo heterozygous missense c.931A > G (p.Ser311Gly) in the TP63 gene classified as pathogenic, and the homozygous nonsense pathogenic c.1810C > T (p.Arg604Ter) in the CNGB3 gene. The same homozygous CNGB3 variation was also found in the sister, explaining the cone dystrophy in both cases. CONCLUSIONS: Whole Exome Sequencing allowed dual molecular diagnoses: de novo TP63-related syndromic ectrodactyly and familial CNGB3-related congenital cone dystrophy.

Shaken adult syndrome due to ocean wave: an autopsy case.

Severe intracranial trauma during torture or assault is reportedly caused by shaken adult syndrome. However, intracranial traumas caused by natural forces, excluding human factors and collision impact, are extremely rare. We report an autopsy case of shaken adult syndrome caused by ocean wave forces. A man in his 40s without any medical history was washed away by a wave during recreational fishing. He was found approximately 500 m away from the fishing point drifting on the ocean in a state of cardiopulmonary arrest and was confirmed dead, with no response to cardiopulmonary resuscitation, 3 h after the accident. The autopsy revealed no mechanical trauma to the entire body surface, including the head. Both lungs were inflated, and pleural effusion was observed. The brain was swollen and congested, and subarachnoid hemorrhage was observed in the interhemispheric fissure and the convexity of the parietal occipital lobe. Macroscopic and microscopic hemorrhage spots were found in the brain, and the results of the blood alcohol test and urinary toxicological screening were negative. The cause of death was determined as drowning. This case demonstrates a rare but notable mechanism of injury observed in immersed bodies.

Improvements in pincer nail deformity occur earlier and last longer when acetylcysteine gel is added to an overcurvature-correcting device: Results of a phase 3, multicenter, randomized, vehicle-controlled, investigator-blinded study.

Acetylcysteine (AC) destabilizes keratin and softens nails, reducing the time needed to correct pincer nail deformity with an overcurvature-correcting device. The objective of this phase 3, multicenter, randomized, investigator-blinded study was to evaluate the early and sustained therapeutic effectiveness and safety of 10% AC gel plus an overcurvature-correcting device to treat pincer nails. Patients aged 12 years and older with hallux pincer nail were fitted with an overcurvature-correcting device for 7 days, with a 24-h application of AC gel (n = 40) or vehicle (n = 39) on day 1. The primary end point (achievement of a distal narrowed nail width ratio ≥70% on day 8) was met by 47.5% in the 10% AC group and 25.6% in the vehicle group (difference 21.9%; p = 0.0439). Secondary end points showed a greater tendency towards improvement with 10% AC. The nail correction effect was maintained for at least 12 weeks in the majority of AC-treated patients, although the study duration was insufficient to assess the long-term probability of recurrence. No AC-related adverse events were reported. In conclusion, a single application of 10% AC gel combined with short-term device use facilitated earlier correction of pincer nails compared with the device alone, with improvements maintained after device removal.

Long-term results of nail correction with double wires for pincer nail deformity: A retrospective cohort study.

There is no consensus on the best treatment for pincer nail deformity. We developed a novel procedure that uses double wires to treat pincer nail deformity on the great toe. This study aimed to describe this technique for pincer nail deformity treatment and present the long-term findings/observations. After injecting a local anesthetic, a mini router was used to make holes on both sides of the nail plate edge, and the wire was inserted in two places, one proximal and the other distal to the great toenail. The wire was removed when it moved to the tip of the great toe as the nail grew. Patients who underwent this method were evaluated retrospectively from 2014 to 2020. Patients with less than 24 months of follow-up were excluded. If pain occurred again, it was deemed as a recurrence. A total of 27 patients (36 toes, mean age: 69.5 years) were evaluated. In all cases, the pain disappeared 1 week after the procedure. In the correction period (mean 2.7 months), six toes had complications (nail break, four toes and nail hold pain, two toes), while recurrence occurred in four toes within 2 years. Curvature (nail tip height/width of nail tip × 100%) improved significantly up to 1-year post-procedure (37.7 ± 14.4%, p < 0.05) as compared to pre-correction (53.8 ± 24.7%). The procedure time was short (approximately 10 minutes), and the treatment was completed with a single procedure. In addition, the recurrence rate was low.

FLOTCH Syndrome: A Case of Leukonychia Totalis and Multiple Pilar Cysts.

FLOTCH (leukonychia totalis-trichilemmal cysts-ciliary dystrophy syndrome) syndrome is a rare genetic cutaneous disorder primarily characterized by multiple recurrent trichilemmal pilar cysts and leukonychia. It may be associated with ciliary dystrophy, koilonychia, and/or less frequently renal calculi and pancreatitis inherited in an autosomal-dominant fashion. We report the case of a 25-year-old Black woman who presented with white-colored fingernails and enlarging cysts in multiple locations including the scalp, rib cage, and forearm and was diagnosed with suspected FLOTCH syndrome. Pilar cysts in unusual locations along with distinct nail changes should prompt clinicians to consider further investigation for conditions such as FLOTCH syndrome.

Nail Discoloration during the COVID-19 Pandemic.

A 45-year-old woman presented to the outpatient dermatology clinic during the COVID-19 pandemic with a painless green discoloration of several fingernails present for 1 week (Figure 1). The patient had no significant past medical history and was not taking any medication. No other findings were noted. There was no history of nail trauma or past fungal infection of the nail. The patient admitted that she had frequent hand washing, given the current pandemic, and never used protective gloves in everyday activities.