Testicular Temperature and the Effects of Orchiopexy in Infants with Cryptorchidism.

PURPOSE: Testicular temperature should remain low to maintain optimal function of germ cells; however, information regarding testicular temperature in infants and the effect of cryptorchidism and its correction, including laparoscopic staged Fowler-Stephens orchiopexy (LSFSO), is limited. MATERIALS AND METHODS: A total of 82 infants with unilateral palpable cryptorchidism, 24 with nonpalpable testes who underwent unilateral LSFSO and 20 with scrotal hydrocele were included. Ultrasonographic determination of testicular volume and measurement of testicular temperature but not scrotal surface temperature using a Coretemp CTM204® (Terumo, Tokyo) were performed before and 12 months after orchiopexy. The effects of the route of testicular delivery, conventionally through a new hiatus medial to the inferior epigastric vessels or through the transinguinal approach, were investigated in the LSFSO cases. RESULTS: Undescended testicular volume was significantly increased after orchiopexy (0.80 ml to 0.92 ml, p <0.0001). The preoperative testicular temperature (35.1C) was significantly higher than that of the control (34.4C, p <0.0001), and significant decreases in testicular temperature occurred after orchiopexy (34.3C, p <0.0001). A multivariate analysis showed that a decrease in testicular temperature was a factor associated with postoperative testicular development. Twelve months after LSFSO, transinguinal approach was shown to be more effective in decreasing the testicular temperature than the conventional approach (34.4 and 35.3C, respectively, p <0.05). CONCLUSIONS: Orchiopexy is effective in correcting the high-temperature environment caused by cryptorchidism. In the case of nonpalpable testes treated by LSFSO, transinguinal fixation is more effective than the conventional approach in reducing testicular temperature, but a longer followup period is necessary to draw a final conclusion.

Testicular torsion and climate changes in macroregions of São Paulo, Brazil.

OBJECTIVE: To analyze the association between climate changes in the macroregions in the state of São Paulo and testicular torsion treated cases. METHODS: The cases were selected in the Brazilian Public Health Data System Database from January 2008 to November 2016. All surgical procedure records were identified by the Hospital Admission Authorization document. Two codes were selected to process the search: testicular torsion (surgical cure code) and acute scrotum (exploratory scrototomy code). The macroregions were grouped in five areas linked to climate characteristics by International Köppen Climate Classification. RESULTS: A total of 2,351 cases of testicular torsion were registered in the period. For the areas B, C and E (testicular torsion n=2,130) there were statistical differences found in association of testicular torsion cases and decreased temperature (p=0.019, p=0.001 and p=0.006, respectively), however, in analyses for the areas A and D statistical differences were not observed (p=0.066 and p=0.494). CONCLUSION: Decrease in temperature was associated with testicular torsion in three macroregions of São Paulo. The findings support the theory of cold weather like a trigger in occurrence of testicular torsion in a tropical climate region.

Testicular torsion and climate changes in macroregions of São Paulo, Brazil / Torção testicular e diferenças climáticas nas macrorregiões do estado de São Paulo, Brasil

ABSTRACT Objective: To analyze the association between climate changes in the macroregions in the state of São Paulo and testicular torsion treated cases. Methods: The cases were selected in the Brazilian Public Health Data System Database from January 2008 to November 2016. All surgical procedure records were identified by the Hospital Admission Authorization document. Two codes were selected to process the search: testicular torsion (surgical cure code) and acute scrotum (exploratory scrototomy code). The macroregions were grouped in five areas linked to climate characteristics by International Köppen Climate Classification. Results: A total of 2,351 cases of testicular torsion were registered in the period. For the areas B, C and E (testicular torsion n=2,130) there were statistical differences found in association of testicular torsion cases and decreased temperature (p=0.019, p=0.001 and p=0.006, respectively), however, in analyses for the areas A and D statistical differences were not observed (p=0.066 and p=0.494). Conclusion: Decrease in temperature was associated with testicular torsion in three macroregions of São Paulo. The findings support the theory of cold weather like a trigger in occurrence of testicular torsion in a tropical climate region.

RESUMO Objetivo: Analisar a associação entre mudanças climáticas nas macrorregiões do estado de São Paulo e os casos tratados com torção testicular registrados. Métodos: Os casos foram selecionados no Banco de Dados do Sistema de Dados de Saúde Pública do Brasil de janeiro de 2008 a novembro de 2016. Todos os registros de procedimentos cirúrgicos foram identificados pelo documento de Autorização de Internação Hospitalar. Dois códigos foram selecionados para processar a busca: torção testicular (código de cura cirúrgica) e escroto agudo (código de escrototomia exploratória). As macrorregiões foram agrupadas em cinco áreas ligadas às características climáticas pela Classificação Internacional de Clima Köppen. Resultados: Foram registrados 2.351 casos de torção testicular no período. Para as áreas B, C e E (torção testicular n=2.130), foram encontradas diferenças estatísticas na associação dos casos de torção testicular e diminuição da temperatura (p=0,019, p=0,001 e p=0,006, respectivamente), mas nas análises das áreas A e D não foram observadas diferenças estatísticas (p=0,066 e p=0,494). Conclusão: A diminuição da temperatura foi associada à torção testicular em três macrorregiões de São Paulo. Os resultados apoiam a teoria do clima frio como um gatilho para ocorrência de torção testicular em uma região de clima tropical.

[Clinical effect of a scrotal rapid recovery dressing device in the treatment of acute epididymitis].

OBJECTIVE: To study the protective effect of a scrotal rapid recovery dressing device, scrotal girdle, on the scrotum of the patient with acute epididymitis, so as to improve the prognosis and the patient's satisfaction. METHODS: A total of 120 patients with acute epididymitis were treated in our hospital from December 2018 to November 2019, 60 with the scrotal girdle plus local cold compress in addition to antibiotics administration (the scrotal girdle group) and the other 60 with antibiotics only (the control group), all for 6 days. Then, comparisons were made between the two groups of patients in the improvement of scrotal swelling, total effectiveness rate and the patients' satisfaction with therapeutic outcomes. RESULTS: After 6 days of treatment, the patients in the scrotal girdle group, compared with the controls, showed significantly lower scrotal swelling scores (1.01 ± 0.34 vs 1.38 ± 0.20, P < 0.05), a higher total effectiveness rate (83.33% vs 65%, P < 0.05) and higher satisfaction with the therapeutic outcomes (86.67% vs 56.67%, P < 0.05). CONCLUSIONS: For the treatment of acute epididymitis, the application of the scrotal girdle for protection can significantly relieve scrotal pain and discomfort, improve the therapeutic effect and patients' satisfaction, and enhance the patients' recovery and quality of life.

Frequent and mild scrotal heat stress in mice epigenetically alters glucose metabolism in the male offspring.

Several studies have reported that health problems occur in assisted reproductive technology (ART)-conceived offspring. Recently, investigations have demonstrated that paternal environmental conditions influence offspring health. However, it is unclear whether the factors that cause male infertility per se affect offspring health and contribute to health problems in ART-born children. Scrotal heat stress represents a common cause for oligoasthenozoospermia, and in these cases, in vitro fertilization-embryo transfer (IVF-ET) is typically recommended for those individuals trying to conceive. We exposed C57BL/6J male mice to frequent and mild scrotal heat stress (fmSHS) (39°C for 30 min once weekly for 5 consecutive wk). Sperm was subjected to IVF-ET with oocytes of untreated C57BL/6J females to produce offspring mice. Glucose intolerance and insulin resistance was observed in the male offspring mice derived from fmSHS-exposed fathers. Islets, after evaluation, remained unchanged. Genes involved in glucose metabolism, especially, those in insulin signaling pathways, showed dysregulation in the liver of the fmSHS-derived male offspring. Differentially methylated regions were found in the sperm of fmSHS-exposed mice by whole genome bisulfite sequencing. Interestingly, abnormal methylation of some genes with altered expression in offspring was observed in both the sperm of fmSHS fathers and the liver of their male offspring. Our results suggest that the factors that cause male infertility can affect male offspring health by an epigenetic mechanism.

Assessment of Age and Duration of Symptoms on Outcomes of Emergency Scrotal Exploration for Acute Scrotal Pain.

OBJECTIVE: To study the effects of age and duration of symptoms on the outcomes of scrotal explorations for acute scrotal pain at our institution. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Bradford Teaching Hospital NHS Trust, from January 2006 to December 2017. METHODOLOGY: Retrospective data was collected from electronic case records of the patients who required scrotal exploration for suspected torsion of the testis. Group difference between continuous variables (age and duration of symptoms) were assessed by Kruskal Wallis and independent samples Mann-Whitney U-tests. The Fisher Exact and Chisquare tests were used to analyse relationships between categorical data. RESULTS: In total, 502 patients required scrotal exploration. The median age (years) and duration of symptoms (hours) were 16.4 years (1.3 - 77) and 4 hours (1 - 336), respectively. Torsion of the testis was found in 231 (46%), torsion of the testicular appendix in 126 (25%), epididymal inflammation in 46 (9.2%), and no cause identified in 99 (19.7%). Immediate orchidectomy for non-viable testis performed in 34 (14.7% of TT group and 6.8% of the overall cohort). Duration of symptoms was significantly associated with risk of orchidectomy in torsion patients 4 vs. 27 hours (p <0.0001). Overall 47 (9.3%) patients presented after 12 hours, 22 (46.8%) had TT. There were 13 (2.6%) patients older than 40 years and 8 (61.5%) of these had torsion. CONCLUSION: The most commonest diagnosis for patients presenting with acute scrotal pain was torsion of the testis followed by torsion of appendix testis. Testicular salvage was inversely related to the duration of symptoms. Patient's age did not predict the need for orchidectomy. This data supports the practice of urgent scrotal exploration for acute scrotal pain with a clinical suspicion of torsion regardless of age and duration of symptoms.

Inguinal Ring RNA Sequencing Reveals Downregulation of Muscular Genes Related to Scrotal Hernia in Pigs.

Scrotal hernias (SH) are common congenital defects in commercial pigs, characterized by the presence of abdominal contents in the scrotal sac, leading to considerable production and animal welfare losses. Since the etiology of SH remains obscure, we aimed to identify the biological and genetic mechanisms involved in its occurrence through the whole transcriptome analysis of SH affected and unaffected pigs' inguinal rings. From the 22,452 genes annotated in the pig reference genome, 13,498 were expressed in the inguinal canal tissue. Of those, 703 genes were differentially expressed (DE, FDR < 0.05) between the two groups analyzed being, respectively, 209 genes upregulated and 494 downregulated in the SH-affected group. Thirty-seven significantly overrepresented GO terms related to SH were enriched, and the most relevant biological processes were muscular system, cell differentiation, sarcome reorganization, and myofibril assembly. The calcium signaling, hypertrophic cardiomyopathy, dilated cardiomyopathy, and cardiac muscle contraction were the major pathways possibly involved in the occurrence of the scrotal hernias. The expression profile of the DE genes was associated with the reduction of smooth muscle differentiation, followed by low calcium content in the cell, which could lead to a decreased apoptosis ratio and diminished muscle contraction of the inguinal canal region. We have demonstrated that genes involved with musculature are closely linked to the physiological imbalance predisposing to scrotal hernia. According to our study, the genes MYBPC1, BOK, SLC25A4, SLC8A3, DES, TPM2, MAP1CL3C, and FGF1 were considered strong candidates for future evaluation.

Calcinose idiopática escrotal: uma inabitual desordem de pele / Idiopathic scrotal calcinosis: an unusual skin disorder

A calcinose escrotal idiopática é uma entidade rara, benigna. Não costuma ter outros sintomas associados. O caso reportado se trata de um paciente de 30 anos com diversos nódulos calcificados em bolsa escrotal, com 15 anos de evolução. Como medida terapêutica, foi realizada excisão cirúrgica completa dos nódulos, apresentando boa evolução cirúrgica e resultados estético e funcional satisfatórios.

Idiopathic scrotal calcinosis is a rare benign entity. Patients affected by scrotal calcinosis usually do not have other associated symptoms. We report the case of a 30-yearold man with several calcified nodules in the scrotal sac with onset at age 15 years. A complete surgical excision of the nodules was performed, and the patient recovered well with satisfactory aesthetic and functional results.

[Acquired undescended testes: treatment and consequences for future fertility]. / Verworven niet-scrotale testis.

1-3% of boys develop an acquired undescended testes (UDT), meaning that the testes cannot be returned into the scrotum after previously having been located in a stable scrotal position. Fertility issues for patients with acquired UDT are comparable to those for patients with congenital UDT. Hypothetically speaking, patients with acquired UDT are at lower risk of testicular cancer than patients with congenital UDT. The appearance of an asymmetrical scrotum, which is associated with UDT, may negatively influence quality of life. Over 50% of the acquired UDTs will spontaneously descend at the start of puberty, thereby justifying conservative management of the condition. Orchidopexy directly after diagnosis does not have any advantages over awaiting spontaneous descent until puberty when fertility in later life of patients with unilateral acquired UDT is concerned; however, it may be beneficial in bilateral acquired UDT.

Novel truncating variants expand the phenotypic spectrum of KAT6B-related disorders.

Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS) and Genitopatellar syndrome (GTPTS) are very rare conditions caused by KAT6B truncating variants. Because of both syndromes often share common features the associated phenotypes are usually grouped under the term "KAT6B-related disorders." However, particular signs of each syndrome have been reported and their appearance seems to be dependent on where the KAT6B variant is located. Thus, whereas truncating variants associated with SBBYSS have their highest density in the distal part of exon 18, those resulting in GTPTS are distributed between the end of exon 17 and beginning of exon 18. Here, we reported two de novo heterozygous KAT6B truncating variants. The first variant (c.5802delA; p.A1935Pfs*16), identified in a boy with SSBYSS phenotype, resulting in the most distal KAT6B truncating variant reported up-to-date in the scientific literature. The second variant (c.3152delG; p.S1051Tfs*63), located in a region hitherto defined as specific of SBBYSS, seems to cause an overlapping SBBYSS/GTPTS phenotype. The clinical and genetic characterization of these patients could contribute to the understanding of the KAT6B-related disorders.

Linfedema crónico escrotal / Chronic scrotal lymphedema

Introducción: el linfedema crónico es una afección de los vasos linfáticos. Puede ser primario debido a hipoplasia linfática, o secundario por obstrucción o rotura de los vasos linfáticos. Entre sus complicaciones están las de tipo infeccioso como la linfangitis, los trastornos tróficos y las neoplasias.Objetivo: presentar el caso de un paciente con linfedema crónico primario escrotal y elefantiasis en la extremidad inferior izquierda, de importancia por la repercusión de las condiciones sociofamiliares de vida en su evolución.Presentación del caso: paciente masculino, blanco, de 57 años, con aumento de volumen en ambas extremidades inferiores -mayor en la izquierda- y en el escroto. Presenta una lesión ulcerosa en los testículos, con secreción maloliente de color verde amarillento, fiebre, pérdida de peso e inapetencia. Fue tratado con antibióticos, curas locales y la nutrición adecuada. Ante la mejoría de la lesión se decidió darle el alta hospitalaria, con recomendaciones profilácticas.Discusión: la enfermedad de este paciente se inició a los siete años de edad, por lo que se trata de un linfedema primario precoz. No se le realizaron los estudios genético ni genealógico familiar. El padecimiento de linfangitis aguda recidivante y la gravedad de la enfermedad, causante de invalidez total, fueron los rasgos clínicos más sobresalientes.Conclusiones: el tratamiento del linfedema crónico no es curativo, y en el caso de este paciente sus condiciones de aislamiento sociofamiliar dificultan una mejoría sostenida. De ahí que se le indicaran medidas profilácticas para evitar la progresión y el empeoramiento de su enfermedad(AU)

Introduction: chronic lymphedema is a condition of the lymphatic vessels. It can be primary due to lymphatic hypoplasia, or secondary due to obstruction or rupture of the lymphatic vessels. Among its complications are those of infectious type such as lymphangitis, trophic disorders and neoplasms.Objective: to present the case of a patient with chronic primary scrotal lymphedema and elephantiasis in the left lower limb, of importance due to the repercussion of socio-family living conditions in its evolution.Case presentation: male patient, white, 57 years old, with increased volume in both lower extremities -major in the left- and in the scrotum. It presents an ulcerous lesion in the testes, with malodorous yellowish-green secretion, fever, weight loss and inappetence. He was treated with antibiotics, local cures and proper nutrition. In view of the improvement of the lesion, it was decided to discharge him, with prophylactic recommendations.Discussion: the disease of this patient began at seven years of age, so it is an early primary lymphedema. No genetic or genealogical family studies were carried out. The condition of recurrent acute lymphangitis and the severity of the disease, causing total disability, were the most outstanding clinical features.Conclusions: the treatment of chronic lymphedema is not curative, and in the case of this patient its socio-familiar isolation conditions hinder a sustained improvement. Hence, prophylactic measures were indicated to prevent the progression and worsening of his disease(AU)

How to Treat Chronic Idiopathic Testicular Pain? Scrotoscopy with a Novel Percutaneous Endoscopy Equipment.

BACKGROUND: Management of chronic idiopathic testicular pain may be difficult because of problems identifying the causes. We evaluated "AUTOKLAV", a novel endourological nephrolithotomy device to diagnose and treat chronic idiopathic testicular pain. METHODS: We divided 103 patients to either scrotoscopy group (SG, n = 64) or open exploration group (OEG, n = 39) between September 2014 and March 2017 at Zhongnan Hospital. Perioperative information, like operating time, length of incision, and wound infections, was carefully recorded during in hospital. Follow-up data, like pain scores improvement, satisfaction with penis appearance, and adverse event, were collected at one month postoperatively. RESULTS: Finally, both the operating time and length of incision showed better performance for SG (43.6 ± 4.7 versus 51.5 ± 9.0 min; 0.7 ± 0.2 versus 4.1 ± 0.8 cm; both P <0.01). Though the pain improvement had no significant differences between the two groups (2.92 ± 0.99 and 2.14 ± 1.02, p>0.05), SG showed obvious advantages in incidence of wound infections and satisfaction with wound/scrotum appearance (0% versus 2.9%; 96.4% versus 85.3%, both P<0.05). CONCLUSIONS: In conclusion, scrotoscopy using the novel AUTOKLAV device is feasible, has an acceptable complication rate, and can be effective and safe in men with idiopathic chronic testicular pain. Etiologically, secondary inflammatory changes caused by the complete or incomplete torsion of testicular or epididymis appendices or by the existence of stones in the tunica sac might be responsible for the pain.

Surgical management of chronic genital lymphoedema.

A 44-year-old man with a spinal cord injury was referred to a specialist urology service with a 7-year history of significant genital swelling. His condition had eluded diagnosis and was refractory to all previous treatments. The considerable swelling both impacted his quality of life and prevented the patient from adequately managing his neurogenic bladder. He was diagnosed with chronic idiopathic genital lymphoedema and underwent total scrotectomy, wide penile skin excision and split skin graft to the penile shaft. The patient made an excellent recovery. We present this unusual case with preoperative, intraoperative and postoperative images.

Case Report: Filaria or Megasperm? A Cause of an Ultrasonographic "Filarial Dance Sign".

Bancroftian filariasis can cause genital abnormalities related to chronic inflammation and obstruction of the afferent lymphatic vessels, and may demonstrate a "filarial dance sign" on scrotal ultrasound with mobile echogenic particles observed. We present a patient with a positive "filarial dance sign," travel within Latin America, and negative filarial serology.

Ovotesticular Disorder of Sex Development Presenting as an Acute Scrotum.

Hermaphroditism is known as ovotesticular disorder of sex development. A 14-year-old boy was admitted with right acute scrotum. Exploration revealed tunica rupture and hematoma, with no viable tissue. After 1 month, he was admitted again with left hemiscrotal pain. Microscopic examination of the left gonad demonstrated foci of hemorrhagic cysts, primordial follicles, and regions of seminiferous tubules. We preserved a testicular tissue and the ovarian part was extracted completely. Long-term follow-up with his hormonal profile is reported. This is a case of ovotesticular disorder presented with acute scrotum and we also tried to reduce long-term hormone therapy, with preservation of testicular part.

Acute scrotum in setting of acute pancreatitis.

Acute scrotum is a urologic emergency with many aetiologies. Acute scrotum in setting of acute pancreatitis is a rare occurrence and results from an effusion of pancreatic juices into the inguinal canal along a retroperitoneal tract. Knowledge regarding the existence of this obscure condition is essential for its diagnosis. It is thus important for medical professionals, particularly internists, surgical trainees and emergency physicians, to be aware of the condition and the options for its management.

Acute appendicitis mimicking acute scrotum: a rare complication of a common abdominal inflammatory disease / Apendicite aguda mimetizando escroto agudo: uma complicação rara de uma doença inflamatória abdominal comum

ABSTRACT Introduction: Acute appendicitis is the most common surgical disease of the abdomen in clinical practice, affecting mainly young adults. It has a wide variety of clinical presentations, due to the anatomical variation of the cecal appendix. Its presentation as acute scrotum and scrotal abscess is quite rare and atypical, occurring mainly in young male patients with patent processus vaginalis. Case presentation: An 18-years-old male patient attended the emergency unit complaining of diffuse abdominal pain, fever and hyporexia for four days followed by inflammatory signs in the scrotum. He was taken to the operation room after diagnosis of scrotal and abdominal sepsis. During scrotum exploration, pus was found inside the right hemiscrotum coming down from the groin and communicating with the abdominal cavity. The laparotomy found perforated appendicitis and peritonitis leading to the scrotal abscess. The abscess was drained, appendectomy was performed and the scrotal and abdominal cavity were washed with saline solution. Despite postoperative complications such as pneumonia and intra-abdominal abscess, the reported patient recovered and was discharged in the 44th postoperative day. Conclusion: Acute appendicitis can mimic acute scrotum and surgeons must have a high index of suspicion of this complication for diagnosing. This unusual clinical presentation may be challenging and can delay the diagnosis leading to perforated peritonitis.

RESUMO Introdução: A apendicite aguda é a doença cirúrgica mais comum do abdome na prática clínica, afetando principalmente adultos jovens. Tem uma grande variedade de apresentações clínicas, devido à variação anatômica do apêndice cecal. Sua apresentação como escroto agudo e abscesso escrotal é bastante rara e atípica, ocorrendo principalmente em pacientes jovens do sexo masculino com túnica vaginalis patente. Apresentação do caso: um paciente do sexo masculino de 18 anos de idade compareceu à unidade de emergência queixando dor abdominal difusa, febre e hiporexia por quatro dias que se seguiram de sinais inflamatórios no escroto. Ele foi levado para centro cirúrgico após o diagnóstico de sepse de origem escrotal e abdominal. Durante a exploração da bolsa escrotal, secreção purulenta foi encontrada do lado direito oriunda do canal inguinal e comunicando-se com a cavidade abdominal. Durante a laparotomia observou-se sinais de apendicite aguda perfurada e peritonite levando ao abscesso escrotal. O abscesso foi drenado, a apendicectomia foi realizada e as cavidades escrotal e abdominal foram lavadas com solução salina. Apesar de complicações pós-operatórias como pneumonia e abscesso intra-abdominal, o paciente recuperou-se bem, recebendo alta hospitalar no 44° dia pós-operatório. Conclusão: A apendicite aguda pode simular o escroto agudo e os cirurgiões devem ter um alto grau de suspeição dessa complicação para o diagnóstico. Esta apresentação clínica incomum pode ser desafiadora e retardar o diagnóstico levando à peritonite por perfuração.

A novel truncating variant within exon 7 of KAT6B associated with features of both Say-Barber-Bieseker-Young-Simpson syndrome and genitopatellar syndrome: Further evidence of a continuum in the clinical spectrum of KAT6B-related disorders.

KAT6B sequence variants have been identified in both patients with the Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS) and in the genitopatellar syndrome (GPS). In SBBYSS, they were reported to affect mostly exons 16-18 of KAT6B, and the predicted mechanism of pathogenesis was haploinsufficiency or a partial loss of protein function. Truncating variants in KAT6B leading to GPS appear to cluster within the proximal portion of exon 18, associated with a dominant-negative effect of the mutated protein, most likely. Although SBBYSS and GPS have been initially considered allelic disorders with distinctive genetic and clinical features, there is evidence that they represent two ends of a spectrum of conditions referable as KAT6B-related disorders. We detected a de novo truncating variant within exon 7 of KAT6B in a 8-year-old female who presented with mild intellectual disability, facial dysmorphisms highly consistent with SBBYSS, and skeletal anomalies including exostosis, that are usually considered component manifestations of GPS. Following the clinical diagnosis driven by the striking facial phenotype, we analyzed the KAT6B gene by NGS techniques. The present report highlights the pivotal role of clinical genetics in avoiding clear-cut genotype-phenotype categories in syndromic forms of intellectual disability. In addition, it further supports the evidence that a continuum exists within the clinical spectrum of KAT6B-associated disorders.