Gland Hypoplasia Research Articles

Severe dry eye due to isolated bilateral lacrimal gland agenesis in a child. A challenging case report and review of the literature

We present a challenging case of severe dry eye secondary to alacrimia due to bilateral lacrimal gland agenesis (LGA) in a child and its successful treatment. A 7-year-old girl presented with symptoms and findings of severe dry eye and keratitis. Systemic associations were excluded, and orbit imaging demonstrated bilateral LGA. Treatment with punctal occlusion, blood-derived and preservative-free eye drops, and PROSE® system/scleral contact lens proved an excellent clinical result. Lacrimal gland hypoplasia is a rare cause of severe dry eye in children. Prompt diagnosis and integral treatment are crucial to reverse ocular surface damage and allow patients to return to their daily activities.

The isl2a transcription factor regulates pituitary development in zebrafish.

ISL LIM homeobox 2, also known as insulin gene enhancer protein ISL-2 (ISL2), is a transcription factor gene that participates in a wide range of developmental events. However, the role of ISL2 in the hypothalamus-pituitary-thyroid axis is largely unknown. In the present study, we characterized the expression patterns of ISL2 and revealed its regulative role during embryogenesis using zebrafish. We used the CRISPR/Cas9 system to successfully establish homozygous ISL2-orthologue (isl2a and isl2b) knockout zebrafish. Moreover, we utilized these knockout zebrafish to analyze the pituitary and thyroid phenotypes in vivo. For further molecular characterization, in situ hybridization and immunofluorescence were performed. The isl2a mutant zebrafish presented with thyroid hypoplasia, reduced whole-body levels of thyroid hormones, increased early mortality, gender imbalance, and morphological retardation during maturity. Additionally, thyrotropes, a pituitary cell type, was notably decreased during development. Importantly, the transcriptional levels of pituitary-thyroid axis hormones-encoding genes, such as tshba, cga, and tg, were significantly decreased in isl2a mutants. Finally, the thyroid dysplasia in isl2a mutant larvae may be attributed to a reduction in proliferation rather than changes in apoptosis. In summary, isl2a regulates the transcriptional levels of marker genes in hypothalamus-pituitary-thyroid axis, and isl2a knockout causing low thyroid hormone levels in zebrafish. Thus, isl2a identified by the present study, is a novel regulator for pituitary cell differentiation in zebrafish, resulting in thyroid gland hypoplasia and phenotypes of hypothyroidism.

Isolated growth hormone deficiency and amenorrhea – Case report

Growth hormone (GH) deficiency is the most common hypopituitarism disorder. We highlight the challenges to its diagnosis and management in the setting of a developing country. A 14-year-old came with a chief complaint of inability to menstruate. Menarche was at 12-years old, lasted 7 days, soaking 2 pads/day which discontinued shortly after. Thelarche was at 12-years-old and her breast is at Tanner stage 3. Her axillary and pubic hair are at Tanner stage 1. Height was 120 cm, weight 34.8 kg, height for age z-score<-3. Her lab results were normal for estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin. Bone age was suitable for age. Magnetic resonance imaging revealed pituitary gland hypoplasia (5.3 mm). A hormonal panel 3 years prior showed abnormally low GH level but normal cortisol and thyroid hormone levels. She was diagnosed with isolated growth hormone deficiency (IGHD) with delayed puberty. She was treated with medroxyprogesterone tablets once daily, after which her menstruation restarted. However, due to her economic background, she declined genetic tests, discontinued her medication and amenorrhea recurred. Amenorrhea present after a brief menarche should alert gynaecologists of a possible multi-hormone disorder with an underlying structural abnormality. IGHD may be due to a structural abnormality, such as pituitary gland hypoplasia. Unfortunately, economic reasons prevented the patient from receiving optimal treatment. IGHD rarely presents with a gynaecological complaint. Hormonal and genetic tests along with imaging should be undertaken. Growth hormone supplementation is the treatment of choice.

Canine hypoadrenocorticism: Case report

Hypoadrenocorticism is an uncommon endocrinopathy which leads to nonspecific, chronic and progressive clinical signs, varying according to the intensity of the disease. The present paper reports the case of a dog with signs of anorexia, greenish-yellow emesis, hypodipsia, hypoglycemia, mild dehydration, abdominal pain and body score 8, which underwent medical care in a private veterinary clinic located in Itu, São Paulo. Laboratory tests were within reference values, but abdominal ultrasonography revealed adrenal gland hypoplasia. Therefore, the patient was referred to an endocrinologist with the diagnostic hypothesis of hypoadrenocorticism and a veterinary nutritionist due to his persistent obesity. Laboratory tests were performed, sodium: potassium ratio and ACTH (adrenocorticotrophic hormone) test, which confirmed the diagnosis of hypoadrenocorticism. The prescribed treatment was fludrocortisone acetate, prednisolone, bezafibrate and silymarin, in which the patient had a considerable improvement in his clinical condition and post-treatment tests. It was concluded that the clinical signs presented, laboratory tests, hormonal dosages and ultrasonographic evaluation were imperative factors for the early diagnosis of this reported case.

Novel Variants and Phenotypes in NEUROG3-Associated Syndrome.

Biallelic pathogenic variants in the NEUROG3 gene cause malabsorptive diarrhea, insulin-dependent diabetes mellitus (IDDM), and rarely hypogonadotropic hypogonadism. With only 17 reported cases, the clinical and mutational spectra of this disease are far from complete. To identify the underlying genetic etiology in 3 unrelated Thai patients who presented with early-onset malabsorptive diarrhea, endocrine abnormalities, and renal defects and to determine the pathogenicity of the newly identified pathogenic variants using luciferase reporter assays and western blot. Three unrelated patients with congenital diarrhea were recruited. Detailed clinical and endocrinological features were obtained. Exome sequencing was performed to identify mutations and in vitro functional experiments including luciferase reporter assay were studied to validate their pathogenicity. In addition to malabsorptive diarrhea due to enteric anendocrinosis, IDDM, short stature, and delayed puberty, our patients also exhibited pituitary gland hypoplasia with multiple pituitary hormone deficiencies (Patient 1, 2, 3) and proximal renal tubulopathy (Patient 2, 3) that have not previously reported. Exome sequencing revealed that Patient 1 was homozygous for c.371C > G (p.Thr124Arg) while the other 2 patients were homozygous for c.284G > C (p.Arg95Pro) in NEUROG3. Both variants have never been previously reported. Luciferase reporter assay demonstrated that these 2 variants impaired transcriptional activity of NEUROG3. This study reported pituitary gland hypoplasia with multiple pituitary hormone deficiencies and proximal renal tubulopathy and 2 newly identified NEUROG3 loss-of-function variants in the patients with NEUROG3-associated syndrome.

Becker’s nevus syndrome: A new case series

Becker’s nevus syndrome (BNS) is a rare epidermal nevus syndrome characterized by Becker’s nevi and other, often unobtrusive, systemic symptoms and/or skin lesions, often ipsilateral. A Becker’s nevus (BN) is a hamartoma that is unilateral, hyperpigmented, and often hairy. Systemic symptoms typically involve breast gland hypoplasia and skeletal and muscular disorders. Herein, we describe three rare cases of Becker’s nevus syndrome. In the first case, the BN coexisted with ipsilateral breast gland hypoplasia; in the second case, the BN coexisted on both sides with breast gland hypoplasia and keratosis pilaris only in the left antecubital region and with scoliosis; in the third case, we found two Becker’s nevi in the left and right hip area associated with hypoplasia of the third canine tooth on the right side and with scoliosis. Our three cases were sporadic and all occurred in males. Coexisting symptoms of BN were found accidentally. We describe two new coexisting symptoms: atypical keratosis pilaris and hypoplasia of the canine teeth.

The EDA-deficient mouse has Zymbal's gland hypoplasia and acute otitis externa.

ABSTRACTIn mice, rats, dogs and humans, the growth and function of sebaceous glands and eyelid Meibomian glands depend on the ectodysplasin signalling pathway. Mutation of genes encoding the ligand EDA, its transmembrane receptor EDAR and the intracellular signal transducer EDARADD leads to hypohidrotic ectodermal dysplasia, characterised by impaired development of teeth and hair, as well as cutaneous glands. The rodent ear canal has a large auditory sebaceous gland, the Zymbal’s gland, the function of which in the health of the ear canal has not been determined. We report that EDA-deficient mice, EDAR-deficient mice and EDARADD-deficient rats have Zymbal’s gland hypoplasia. EdaTa mice have 25% prevalence of otitis externa at postnatal day 21 and treatment with agonist anti-EDAR antibodies rescues Zymbal’s glands. The aetiopathogenesis of otitis externa involves infection with Gram-positive cocci, and dosing pregnant and lactating EdaTa females and pups with enrofloxacin reduces the prevalence of otitis externa. We infer that the deficit of sebum is the principal factor in predisposition to bacterial infection, and the EdaTa mouse is a potentially useful microbial challenge model for human acute otitis externa.

Cutaneous Effects of In Utero and Lactational Exposure of C57BL/6J Mice to 2,3,7,8-Tetrachlorodibenzo-p-dioxin.

To determine the cutaneous effects of in utero and lactational exposure to the AHR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), pregnant C57BL/6J mice were exposed by gavage to a vehicle or 5 μg TCDD/kg body weight at embryonic day 12 and epidermal barrier formation and function were studied in their offspring from postnatal day 1 (P1) through adulthood. TCDD-exposed pups were born with acanthosis. This effect was AHR-dependent and subsided by P6 with no evidence of subsequent inflammatory dermatitis. The challenge of adult mice with MC903 showed similar inflammatory responses in control and treated animals, indicating no long-term immunosuppression to this chemical. Chloracne-like sebaceous gland hypoplasia and cyst formation were observed in TCDD-exposed P21 mice, with concomitant microbiome dysbiosis. These effects were reversed by P35. CYP1A1 and CYP1B1 expression in the skin was increased in the exposed mice until P21, then declined. Both CYP proteins co-localized with LRIG1-expressing progenitor cells at the infundibulum. CYP1B1 protein also co-localized with a second stem cell niche in the isthmus. These results indicate that this exposure to TCDD causes a chloracne-like effect without inflammation. Transient activation of the AhR, due to the shorter half-life of TCDD in mice, likely contributes to the reversibility of these effects.

ADAMTS18 deficiency leads to preputial gland hypoplasia and fibrosis in male mice

ADAMTSs (A disintegrin and metalloproteinase with thrombospondin motifs) are a family of 19 secreted zinc metalloproteinases that play a major role in the assembly and degradation of the extracellular matrix (ECM) during development, morphogenesis, tissue repair, and remodeling. ADAMTS18 is a poorly characterized member of the ADAMTS family. Previously, ADAMTS18 was found to participate in the development of female reproductive tract in mice. However, whether ADAMTS18 also plays a role in the development of male reproductive system remains unclear. In this study, Adamts18 mRNA was found to be highly expressed in the basal cells of the developing preputial gland. Male Adamts18 knockout (Adamts18−/−) mice exhibit abnormal preputial gland morphogenesis, including reduced size and sharp outline. Histological analyses of preputial gland from 2-week-old male Adamts18−/− mice showed significant atrophy of the whole gland. Preputial glands from 7 months and older Adamts18−/− mice appeared macroscopic swelling on their surface. Histologically, preputial gland swelling is characterized by tissue fibrosis and thicker keratinized squamous cell layer. Preputial gland lesions in age-matched male Adamts18+/+ mice were barely detected. ADAMTS18 deficiency does not lead to significant changes in morphogenesis of prostate and testis in male mice. These results indicate that ADAMTS18 is required for normal morphogenesis and homeostasis of the preputial gland in male mice.

Congenital Hypothyroidism: Space-Time Clustering of Thyroid Dysgenesis Indicates a Role for Environmental Factors in Disease Etiology.

Background: The etiology of most cases of congenital hypothyroidism (CHT) due to thyroid dysgenesis (DG) is unknown. If transient environmental factors can impact on thyroid gland development, then clustering of cases in time and/or space may occur, and this would be more likely in thyroid DG than dyshormonogenesis (DHG).Methods: The newborn screening program for CHT in Scotland is linked to a central database that includes case details such as postcode. The etiology of CHT is investigated in many cases of CHT using scintigraphy and/or ultrasonography. We looked for evidence of a change in CHT incidence with year of birth and according to season of the year. We then undertook space–time clustering analysis (using a method based on K-functions, with nearest neighbor thresholds) of CHT in Scotland between 1979 and 2015. We also looked for evidence of overall changes associated with sex and area-based birth density.Results: Of 531 cases with CHT during the study period, 290 cases had been categorized as DG (n = 229) or DHG (n = 61) following more detailed investigation. The incidence of CHT increased with year of birth and was in part linked to changing methodology, but there was no seasonality. There was no evidence of overall space–time clustering (p = 0.06), but there was evidence of clustering in babies with DG (p = 0.007). This picture appeared to be most closely linked to underlying thyroid gland hypoplasia rather than thyroid gland agenesis or ectopia. There was significant space–time clustering for both males and females, but clustering was restricted to lesser birth density areas. There was also evidence of clustering for unknown cases (p < 0.001). Clustering of these cases was restricted to females but was present for cases from both greater and lesser birth density areas. There was no evidence of clustering in cases of DHG.Conclusions: These data suggest that an unidentified environmental factor or factors may be involved in the etiology of thyroid DG in Scotland. The variation in CHT incidence observed internationally may reflect environmental as well as genetic factors.

Is There an Association Between Breast Hypoplasia and Breastfeeding Outcomes? A Systematic Review.

Introduction: Insufficient milk supply is the most common reason for premature breastfeeding cessation. Breast hypoplasia is one reason why women may be inherently unable to make a full milk supply. This review aimed to systematically explore the relationship between breast hypoplasia and breastfeeding duration, milk supply, and lactation onset. Materials and Methods: Medline, CINAHL, ProQuest Central, and the Cochrane Library databases were searched using the keywords "insufficient glandular tissue" or "mammary hypoplasia" or "breast hypoplasia" or "mammary gland hypoplasia" or "droopy breasts" or "snoopy deformity" or "tubular breast*" or "tuberous breast*" AND breastfeeding or "breast feeding" or breast-feeding or lactation. After initially screening 20 records, including reference lists, 9 full texts were assessed for eligibility; 2 were excluded as no breastfeeding outcomes were reported, leaving 7 studies (N = 42 women). Results: The studies in this review drew on results from the oldest included study and plastic surgery literature to define breast hypoplasia. Most women in this review (40/42) ceased exclusive breastfeeding before 1 month postpartum. One case study reported 24-hour milk production, which was 52 mL at 26 weeks postpartum. Conclusion: The relationship between breast hypoplasia and breastfeeding outcomes is underresearched. The co-occurring medical conditions (e.g., polycystic ovary syndrome) of some women provide avenues for future research into the possible pathogenesis of breast hypoplasia resulting in insufficient milk supply. Research is needed to evaluate the reliability of measuring and classifying markers of breast hypoplasia, and prospective studies can help determine the role of breast hypoplasia in milk production. PROSPERO registration number CRD42020191228.

Genotypic and phenotypic variability of 22q11.2 microdeletions - an institutional experience.

Patients with chromosome 22q11.2 deletion syndromes classically present with variable cardiac defects, parathyroid and thyroid gland hypoplasia, immunodeficiency and velopharyngeal insufficiency, developmental delay, intellectual disability, cognitive impairment, and psychiatric disorders. New technologies including chromosome microarray have identified smaller deletions in the 22q11.2 region. An increasing number of studies have reported patients presenting with various features harboring smaller 22q11.2 deletions, suggesting a need to better elucidate 22q11.2 deletions and their phenotypic contributions so that clinicians may better guide prognosis for families. We identified 16 pediatric patients at our institution harboring various 22q11.2 deletions detected by chromosomal microarray and report their clinical presentations. Findings include various neurodevelopmental delays with the most common one being attention deficit hyperactivity disorder (ADHD), one reported case of infant lethality, four cases of preterm birth, one case with dual diagnoses of 22q11.2 microdeletion and Down syndrome. We examined potential genotypic contributions of the deleted regions.

Long-term postnatal outcome of fetuses with prenatally suspected septo-optic dysplasia.

ABSTRACTObjectivesSepto‐optic dysplasia (SOD) is a clinical syndrome characterized by varying combinations of optic nerve hypoplasia, pituitary gland hypoplasia and abnormal cavum septi pellucidi. It is suspected on prenatal imaging when there is non‐visualization or hypoplasia of the septal leaflets. Long‐term postnatal outcomes of fetuses with prenatally suspected SOD have been documented poorly. The aims of this study were to describe the natural history of deficient septal leaflets, to quantify the incidence of postnatally confirmed SOD and to document the visual, endocrine and long‐term neurodevelopmental outcomes of these infants.MethodsThis was an observational retrospective study of all fetuses with prenatal imaging showing isolated septal agenesis, assessed at a single tertiary center over an 11‐year period. Pregnancy, delivery and neonatal outcomes and pre‐ and postnatal imaging findings were reviewed. Neonatal evaluations or fetal autopsy reports were assessed for confirmation of SOD. Ophthalmologic, endocrine, genetic and long‐term developmental evaluations were assessed. Imaging findings and outcome were compared between infants with and those without postnatally confirmed SOD.ResultsOf 214 fetuses presenting with septal absence on prenatal ultrasound and magnetic resonance imaging (MRI), 18 (8.4%) were classified as having suspected isolated septal agenesis suspicious for SOD. Uniform prenatal MRI findings in cases with suspected SOD included remnants of the leaflets of the cavum septi pellucidi, fused forniceal columns, normal olfactory bulbs and tracts and a normal optic chiasm. Twelve fetuses were liveborn and five (27.8%) had postnatally confirmed SOD. Only two of these five fetuses had additional prenatal imaging features (pituitary cyst, microphthalmia and optic nerve hypoplasia) supporting a diagnosis of SOD. The other three confirmed SOD cases had no predictive prenatal or postnatal imaging findings that reliably differentiated them from cases without confirmed SOD. Visual and endocrine impairments were present in two (40%) and four (80%) cases with confirmed SOD, respectively. In those with visual and/or endocrine impairment, developmental delay (median age at follow‐up, 2.5 (interquartile range, 2.5–7.0) years) was common (80%) and mostly severe. Neonates with isolated septal agenesis and a lack of visual or endocrine abnormalities to confirm SOD had normal development.ConclusionsOnly a quarter of fetuses with isolated septal agenesis suggestive of SOD will have postnatal confirmation of the diagnosis. Clinical manifestations of SOD are variable, but neurodevelopmental delay may be more prevalent than thought formerly. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Novel phenotype of syndromic premature ovarian insufficiency associated with TP63 molecular defect.

There is growing evidence that TP63 is associated with isolated as well as syndromic premature ovarian insufficiency (POI). We report two adolescent sisters diagnosed with undetectable ovaries, uterine hypoplasia, and mammary gland hypoplasia. A novel paternally inherited nonsense variant in TP63 [NM_003722.4 c.1927C > T,p.(Arg643*)] in exon 14 was identified by exome sequencing. One of the syndromes linked to TP63 is limb mammary syndrome (LMS), an autosomal dominant inherited disorder characterized by ectrodactyly, hypoplasia of mammary-gland and nipple, lacrimal duct stenosis, nail dysplasia, dental anomalies, cleft palate and/or cleft lip and absence of skin and hair defects. The TP63 variant segregated with symptoms of LMS in the family, however, no affected individual had limb defects. The phenotype reported here represents a novel syndromic phenotype associated with TP63. Reported cases with TP63 associated POI are reviewed.

Combined Mastopexy and Augmentation with Autologous Fat Grafting: First Results with Lipopexy.

The treatment of breast ptosis and gland hypoplasia in a single surgery is a challenging procedure and the result is less predictable. In this surgery, the complications mainly concern the prosthesis, such as implant deflation, capsular contracture, palpability, or malposition. We, therefore, propose a different and new technique that avoids breast prosthesis, combining mastopexy and autologous augmentation with fat grafts. Combined mastopexy and autologous fat graft augmentation (lipopexy) was performed in women affected by breast ptosis and asymmetric breast or hypomastia. The breast lift technique was determined due to the ptosis level. The process of fat grafting was executed according to the PureGraft and, in some cases, to GID System, to Celution System or Carraway's techniques. Thirty-four patients affected by breast ptosis and hypomastia underwent lipopexy from January 2010 to May 2017. The mean volume of adipose tissue injected for each breast was 225.98 ml. After surgery, the patients were followed for an average of 22.8 months. A mild ptosis relapse with partial fat absorption was observed in 4 cases (11.76%) and the presence of oily cysts was diagnosed in 2 patients (5.88%). One severe complication was recorded (hematoma drainage). All the patients healed uneventfully in 2 weeks. This technique allows the surgeon to distribute the desired fat volume along the breasts, avoids implants, and displayed stable results. This treatment has been demonstrated not to interfere with follow-up breast imaging. We, therefore, consider lipopexy a valuable and safe alternative to mastopexy and mild to moderate breast volume augmentation.

Septo-optic dysplasia with amniotic band syndrome sequence: a case report

IntroductionDe Morsier syndrome, or septo-optic dysplasia, is a rare, heterogeneous, complex condition with a highly variable phenotype. It is characterized by optic nerve hypoplasia, pituitary gland hypoplasia, and midline brain abnormalities, including absence of septum pellucidum and corpus callosum dysgenesis. Diagnosis is made clinically by the presence of any two or more features from the clinical triad.Case presentationWe report a case of a premature African newborn male baby born to nonconsanguineous parents who presented to our institution with agenesis of the septum pellucidum, unilateral optic nerve hypoplasia, and pituitary stalk hypoplasia. However, he had intact central endocrine function. He also presented with limb defects due to constricting amniotic band syndrome. Other dysmorphic features were low-set ears, microcephaly, and bilateral talipes equinovarus. He otherwise had a normal neurological examination result. Over time, he had an adequate weight gain and was managed by a multidisciplinary team.ConclusionDe Morsier syndrome still represents a diagnostic challenge, despite advances in neuroimaging and genetic studies, due to the heterogeneous nature of the disorder. This case adds to existing knowledge on the vascular pathogenesis of septo-optic dysplasia.

Septo-optic dysplasia caused by a novel FLNA splice site mutation: a case report

BackgroundSepto-optic dysplasia (SOD), also known as de-Morsier syndrome, is a rare disorder characterized by any combination of optic nerve hypoplasia, pituitary gland hypoplasia, and midline abnormalities of the brain including absence of the septum pellucidum and corpus callosum dysgenesis. The variable presentation of SOD includes visual, neurologic, and/or hypothalamic-pituitary endocrine defects. The unclear aetiology of a large proportion of SOD cases underscores the importance of identifying novel SOD-associated genes.Case presentationTo identify the disease-causing gene in a male infant with neonatal hypoglycaemia, dysmorphic features, and hypoplasia of the optic nerve and corpus callosum, we designed a targeted next-generation sequencing panel for brain morphogenesis defects. We identified a novel hemizygous deletion, c.6355 + 4_6355 + 5delAG, in intron 38 of the FLNA gene that the patient had inherited from his mother. cDNA studies showed that this variant results in the production of 3 aberrant FLNA transcripts, the most abundant of which results in retention of intron 38 of FLNA.ConclusionsWe report for the first time a case of early-onset SOD associated with a mutation in the FLNA gene. This finding broadens the spectrum of genetic causes of this rare disorder and expands the phenotypic spectrum of the FLNA gene.

656 Psoriasis and obesity: Stearoyl-CoA desaturase 1 deficient mice are resistant to imiquimod-induced psoriasiform dermatitis

Psoriasis is a chronic inflammatory skin condition whose severity has been linked with obesity. In patients with psoriasis, the likelihood of developing new-onset obesity is higher than those without psoriasis. Stearoyl-CoA desaturase (SCD), is an endoplasmic reticulum resident desaturase, that acts as a catalyst in the synthesis of monounsaturated fatty acids. Mice lacking SCD1 are insulin sensitive, resistant to development of obesity and exhibit suppressed fatty acid synthesis. We have earlier shown that skin specific deletion of SCD1 in mice (SKO) results in epidermal proliferation, sebaceous gland hypoplasia and elevated interleukin 6 levels. We hypothesized that SCD1 deficiency will render mice susceptible to imiquimod (IMQ)-induced psoriasiform dermatitis. A topical dose of 62.5 mg IMQ cream was applied daily to the shaved back region of SKO and SCD1 proficient FLOX counterparts for 14 days after which the mice were euthanized. Cumulative average skin thickness in SKO animals following IMQ application, measured prior to excision was significantly (36%) less than that in FLOX animals. Quantitation of epidermal thickness in H&E stained skin sections validated this observation. Further, histological analysis revealed that in spite of skin inflammation and hair follicle dysplasia associated with their genetic background, the degree of IMQ associated inflammatory changes in the SKO mice were remarkably less than that in FLOX counterparts. Keratin 14, the prototypic marker of dividing basal keratinocytes was elevated in IMQ-treated FLOX skin. Moreover, fatty acid binding protein 5, upregulated in psoriasis tissue was reduced in SKO skin. Our data suggests a complex relationship between fatty acid metabolism and cytoskeletal proteins driving aberrant cell proliferation in psoriatic skin. We propose that SCD1 inhibition could be a novel approach for the management of psoriasis, especially in obese individuals.

Hypogonadotropic hypogonadism and pituitary hypoplasia as recurrent features in Ulnar-Mammary syndrome.

Ulnar-mammary syndrome (UMS) is characterized by ulnar defects, and nipple or apocrine gland hypoplasia, caused by TBX3 haploinsufficiency. Signs of hypogonadism were repeatedly reported, but the mechanisms remain elusive. We aim to assess the origin of hypogonadism in two families with UMS. UMS was suspected in two unrelated probands referred to an academic center with delayed puberty because of the evident ulnar ray and breast defects in their parents. Clinical, biochemical and genetic investigations proved the existence of congenital normosmic IHH (nIHH) associated with pituitary hypoplasia in the two probands who were heterozygous for novel TBX3 pathogenic variants. The mutations co-segregated with delayed puberty, midline defects (nose, teeth and tongue anomalies) and other variable features of UMS in the two families (absent axillary hairs and nipple hypoplasia, asymmetrical features including unilateral ulnar or renal abnormalities). The combined analysis of these findings and of the previous UMS reports showed delayed puberty and other signs of hypogonadism in 79 and 37% of UMS males, respectively. Proband 1 was followed up to adulthood with persistence of nIHH. In conclusion, UMS should be suspected in patients with delayed puberty and midline defects, including pituitary hypoplasia, in the presence of mild cues for TBX3 mutation, even in the absence of limb malformations. In addition, TBX3 should be included among candidate genes for congenital nIHH.

New insights into the phenotypic spectrum of 14q22q23 deletions: a case report and literature review

BackgroundMutations occurring in the orthodenticle homeobox 2 gene (OTX2) are responsible for a rare genetic syndrome, characterized mainly by microphthalmia/anophthalmia associated with extra-ocular defects such as brain malformations, pituitary abnormalities, short stature and intellectual disability. To date, the spectrum of radiological features observed in patients with OTX2 mutations has never been summarized.Case presentationIn this report, we describe a case of large microdeletion encompassing OTX2 but not BMP4 presenting with a syndromic anophthalmia with corpus callosum hypoplasia, pituitary gland hypoplasia and vermian hypoplasia.ConclusionOur case report provides an illustration of the neuroradiological spectrum in a case of OTX2-related syndrome and the first radiological evidence of 14q22.2q23.1 deletion associated posterior cranial fossa anomalies.