Multicystic dysplastic kidney (MCDK) is a congenital renal anomaly identified on prenatal ultrasound. They often arise sporadically and unilaterally. Our case involves an isolated unilateral MCDK in a fetus born to a mother with generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), and gastroesophageal reflux disease (GERD), with the father having chronic occupational lead exposure and a congenital disorder of glycosylation type 1A (PMM2-CDG). Our case highlights the multifactorial etiology of renal dysplasia and its potential role of glycosylation defects and environmental toxicity in abnormal kidney development. Contributions from genetic, environmental, and metabolic influences during nephrogenesis contribute to MCDK.

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a rare congenital anomaly of the Müllerian ducts and represents the second most common cause of primary amenorrhea, accounting for 10%-15% of cases. Despite its significance, limited data exist regarding its clinical profile and associated anomalies in the Indian population. This study aims to determine the prevalence of MRKH syndrome among women presenting with primary amenorrhea at a tertiary care center in South India and to describe their clinical profiles and associated anomalies using the Vagina Cervix Uterus Adnexa-associated Malformation (VCUAM) classification system. A retrospective study was conducted over 15 years (January 2008 to December 2022) including women diagnosed with MRKH syndrome based on inclusion criteria: primary amenorrhea, normal secondary sexual characteristics, 46-XX karyotype, and normal serum follicle-stimulating hormone levels. Data were extracted from medical records and analyzed using SPSS v25.0. Out of 340 women with primary amenorrhea, 181 (60%) were diagnosed with MRKH syndrome. The mean age at presentation was 21 years. The predominant complaint was non-attainment of menarche (66.8%), with 16.5% reporting cyclical abdominal pain. Type 1 MRKH was most common (78.9%), followed by Müllerian duct aplasia-renal agenesis-cervicothoracic somite dysplasia (MURCS) association (16.5%). Renal anomalies (15.5%) were the most frequent extragenital malformations. All women had vaginal and cervical agenesis (V5bC2b). Uterine anomalies included bilateral aplasia (89.1%), unilateral aplasia (0.6%), and hypoplasia (10.5%). MRKH syndrome is a significant cause of primary amenorrhea, with notable extragenital anomalies, especially renal. Systematic evaluation using the VCUAM classification enables comprehensive assessment, aiding in individualized and multidisciplinary care strategies.

There is no clear guidance on prenatal diagnostic testing strategies for congenital renal anomalies. Therefore, this study aims to investigate the retrospective analysis of ultrasound and genetic diagnostic results in cases of fetal renal abnormalities and to establish genotype-phenotype correlations. A total of 329 fetuses with renal abnormalities that underwent prenatal diagnostic testing from January 2020 to April 2023 were recruited in this study. These cases were classified into 11 subgroups based on their ultrasound diagnosis. All cases underwent chromosomal microarray analysis (CMA) or copy number variation sequencing (CNV-seq), with subsequent whole exome sequencing (WES) conducted on select CMA/CNV-seq negative cases, subject to parental consent for further testing targeting monogenic variations. Of the 329 cases analyzed, CMA/CNV-seq detected chromosomal abnormalities in 31 cases, with a detection rate of 9.4% (31/329). The most common abnormality was 17q12 deletion, accounting for 29% of the positive cases (9/31) and 2.7% of the total cases (9/329). WES was conducted on 76 cases (76/298, 25.5%), revealing 16 monogenic variants, and 2 CNVs in 12 cases (15.8%). An overall positive diagnostic yield of 13.1% (43/329) was obtained in the pipeline of combinational CMA/CNV-seq and WES analysis. Ciliary genes (TMEM67, NPHP3, CEP290, BBS2, and TTC8) were frequently implicated by WES. Several genotype-phenotype correlations emerged, including (1) hyperechogenic kidneys associated with 17q12 deletion, (2) renal dysplasia, renal cysts, hydronephrosis, ectopic kidney, and renal duplication with chromosomal abnormalities, (3) unilateral renal agenesis and polycystic kidneys with monogenic variants. This study reveals genotype-phenotype correlations in fetal renal abnormalities, informing prenatal counseling regarding diagnostic testing options and expected outcomes.

This case series explores the diagnostic overlap between OHVIRA syndrome (obstructed hemivagina and ipsilateral renal anomaly) and Gartner duct cyst (GDC) with ipsilateral renal dysplasia in two prepubertal girls. Both cases exhibited similar imaging features on CT and MRI-including unilateral renal agenesis, ectopic ureter with abnormal insertion, cystic lesions posterolateral to the bladder- which led to significant diagnostic challenges. Despite differing in pathology, the overlap in embryologic origins and imaging findings made differentiation difficult. This series underscores the importance of comprehensive imaging and a multidisciplinary approach for accurate diagnosis. Current management strategies are discussed, highlighting the need for individualized treatment plans in prepubertal patients with complex genitourinary anomalies. Cat eye syndrome (CES), also known as Schmid-Fraccaro syndrome, is a rare genetic disorder named for the vertical iris coloboma observed in some affected individuals. The condition is classically characterized by a triad of features—iris coloboma, anal atresia, and preauricular pits or tags. However, CES can also involve a range of abnormalities affecting the neurodevelopmental, ocular, auricular, nasal, cardiovascular, gastrointestinal, and urogenital systems (see Image. Schematic Diagram Showing Iris Coloboma in Cat Eye Syndrome).  The clinical presentation of CES is variable, with differences in affected organ systems, prognosis, genetics, and heritability among individuals. CES is a rare chromosomal disorder first described in the early 1960s by Schmid and Fraccaro. This condition is characterized by a partial tetrasomy or trisomy of chromosome 22q11.1-q11.2. The name "cat eye" originates from ocular colobomas—iris defects—present in about half of affected individuals, which give the pupil a distinctive keyhole or cat-eye appearance. Although ocular coloboma is the eponymous hallmark, CES is fundamentally a multisystem genomic disorder with highly variable expressivity, spanning a spectrum from nearly asymptomatic to severe anomalies across ocular, cardiac, renal, gastrointestinal, skeletal, and neurodevelopmental domains. The association between ocular coloboma and anal atresia was first described by Haab in 1878. The genetic alteration is due to a small supernumerary marker chromosome (sSMC), which was first described in 1965. Schachenmann et al reported 3 pediatric patients and 1 patient’s mother who carried an additional, abnormally small chromosome featuring a submedian centromere, while the rest of the karyotype appeared normal. This sSMC contains the CES critical region (CESCR), located within the proximal portion of chromosome 22q11.2, between the centromere and the LCR22-A region. Additional genetic conditions related to chromosome 22 include the oculo-auriculo-vertebral spectrum (OAVS), DiGeorge syndrome, and mosaic trisomy 22.  At the genetic level, CES arises from a supernumerary marker chromosome, often dicentric, composed of material from chromosome 22. In approximately 90% of cases, this marker contains 2 extra copies of the proximal 22q11 region (tetrasomy), while a smaller proportion exhibits an additional copy (trisomy). The critical region encompasses approximately 1.5 to 2 Mb and includes multiple dosage-sensitive genes whose overexpression is believed to contribute to the diverse phenotypic features of CES. Molecular cytogenetic techniques, such as fluorescence in situ hybridization (FISH), array comparative genomic hybridization (aCGH), and, more recently, genome-wide single-nucleotide polymorphism (SNP) microarrays, have replaced traditional karyotyping for precise delineation of the supernumerary chromosome and identification of the breakpoints. This high-resolution genomic mapping is crucial for definitive diagnosis, genotype-phenotype correlations, and recurrence-risk counseling. Clinically, CES is remarkably heterogeneous. The classic triad comprises iris coloboma, preauricular skin tags or pits, and anal atresia or other anorectal malformations. However, no single feature is universally present. Iris coloboma appears in 40% to 60% of cases, preauricular anomalies in up to 70%, and anorectal malformations in about 30% to 50%. Cardiac defects, most commonly total or partial atrioventricular septal defects and tetralogy of Fallot, occur in approximately half of patients and are a major contributor to early morbidity and mortality. Renal anomalies, reported in 20% to 40% of cases, may include unilateral renal agenesis, duplex collecting systems, hydronephrosis, and vesicoureteral reflux. Skeletal abnormalities range from vertebral segmentation defects to limb anomalies. Otolaryngological manifestations may include hearing loss from middle-ear dysplasia. Less commonly, gastrointestinal anomalies beyond anorectal malformations—such as duodenal atresia or Hirschsprung disease—have also been documented. Neurodevelopmental outcomes in CES vary widely. Although some children achieve developmental milestones within normal limits, others present with global developmental delay, intellectual disability, or features consistent with autism spectrum disorder. Hypotonia during infancy and feeding difficulties—often related to underlying gastrointestinal anomalies—may further compromise early growth. Growth parameters can be affected, with some patients exhibiting short stature or failure to thrive; however, many ultimately achieve normal height and weight. Behavioral phenotypes—such as attention-deficit/hyperactivity disorder (ADHD) and anxiety disorders—have also been reported, emphasizing the importance of comprehensive developmental and psychological assessment. Ophthalmic manifestations in CES extend beyond the iris coloboma. Additional anomalies such as chorioretinal colobomas, microphthalmia, cataracts, microcornea, and strabismus can contribute to visual impairment. A comprehensive ophthalmologic evaluation includes slit-lamp biomicroscopy to assess anterior segment abnormalities, indirect ophthalmoscopy for posterior segment examination, and optical coherence tomography (OCT), when available, to delineate the extent of colobomatous defects. Early detection and management of refractive errors, amblyopia, and strabismus are essential to support optimal visual development. Surgical intervention for coloboma is rarely indicated and is typically reserved for cases involving severe aniridia-like photophobia or significant cosmetic concerns (see Image. Schematic Diagram Showing Chorioretinal Coloboma in Cat Eye Syndrome). The management of CES depends on the organ systems involved and the severity of associated malformations. Given the significant clinical heterogeneity, an individualized, interprofessional approach is essential. This activity outlines the genetic and phenotypic spectrum of CES and outlines strategies for tailoring medical care to each patient’s needs. Cardiac evaluation at diagnosis is mandatory. Echocardiography within the first weeks of life is essential for detecting structural heart disease; in moderate-to-severe cases, surgical repair during infancy may be lifesaving. Long-term cardiology follow-up is critical to monitor for residual defects, arrhythmias, and pulmonary hypertension. Similarly, early renal ultrasonography is recommended to identify anatomical anomalies, guide urologic management, and prevent complications such as hypertension or renal insufficiency. Gastroenterological and colorectal management primarily focuses on anorectal malformations. Posterior sagittal anorectoplasty (PSARP) is the standard repair for imperforate anus, with timing and technical details tailored to the patient’s specific anatomy and overall health. Nutritional support—ranging from gavage or gastrostomy feeding in neonates to dietary modifications in older children—is essential, especially when gastrointestinal motility disorders or malabsorption are present. Audiologic and otologic care begins with newborn hearing screening. Conductive hearing loss due to middle ear anomalies may require interventions such as tympanostomy tubes or myringotomy. Speech therapy and educational support, tailored to the child’s developmental needs, are essential for optimizing communication outcomes. Genetic counseling for families includes discussion of recurrence risk, which is generally low (<1%) in de novo cases but higher in familial instances when a parent carries the small supernumerary marker chromosome in a balanced form. Secondary complications may include endocrine disorders, particularly growth hormone deficiency and thyroid dysfunction, necessitating regular endocrinologic screening. Orthopedic evaluations focus on detecting scoliosis and limb-length discrepancies. Dental and orthodontic assessments help identify malocclusion and enamel hypoplasia. Psychosocial support for families—including referrals to patient advocacy groups and peer support networks—promotes coping strategies and shared experiences. From a research perspective, CES provides valuable insights into gene dosage effects in contiguous-gene syndromes. The 22q11 region implicated in CES overlaps with that of DiGeorge syndrome (22q11.2 deletion), yet their phenotypes differ, reflecting divergent consequences of haploinsufficiency versus gene overexpression. Current studies focus on elucidating the roles of candidate genes such as CECR1 (which encodes adenosine deaminase 2) and CECR2 (involved in chromatin remodeling) in contributing to CES manifestations. Animal models with targeted duplications of the 22q11 region are under development to investigate relevant developmental pathways. Additionally, next-generation sequencing techniques show promise in detecting cryptic rearrangements and refining genotype–phenotype correlations, ultimately improving prognostic accuracy and identifying potential therapeutic targets. In summary, CES is a complex, multisystem chromosomal disorder. While its hallmark features include ocular coloboma, ear anomalies, and anorectal malformations, the condition also encompasses a wider phenotypic spectrum affecting the cardiac, renal, skeletal, neurodevelopmental, and endocrine systems. Accurate diagnosis relies on high-resolution cytogenetic and molecular techniques. Effective management requires coordinated multidisciplinary care, involving specialties from neonatology and cardiology to ophthalmology, urology, and developmental pediatrics. As advances in molecular genetics continue, they will enhance personalized prognostic counseling and enable the development of targeted therapies, ultimately improving outcomes for individuals and families affected by this rare but informative genomic syndrome.

Inguinal hernia in females is an uncommon entity. While most patients present in infancy or early in childhood, only a few cases are diagnosed in adulthood. Most cases of inguinal hernia have small bowel or omentum as its content. Herniation of the ovary or fallopian tube is rare. In our case, an 18-year-old female presented to the outpatient department with unilateral inguinal swelling, which on imaging was found to be ovarian inguinal herniation. This prompted further evaluation. There was an associated absence of the uterus and left kidney, and congenital block vertebrae involving the cervical spine. On probing it was found that she had primary amenorrhoea with normal secondary sexual characteristics. All the findings led to the diagnosis of Mayer Rokitansky Kuster Hauser type II or Mullerian duct aplasia renal agenesis cervicothoracic somite dysplasia (MURCS) with unilateral inguinal ovarian herniation. Mullerian duct aplasia renal agenesis cervicothoracic somite dysplasia (MURCS) present a challenge as they require a multidisciplinary team including gynaecologist, surgeon and psychologist to preserve the ovarian function and help the patient counsel regarding the reproductive outcome and wade through the associated emotional stress. FREM1 autosomal recessive disorders include Manitoba oculotrichoanal (MOTA) syndrome, bifid nose with or without anorectal and renal anomalies (BNAR) syndrome, and isolated congenital anomalies of kidney and urinary tract (CAKUT). MOTA syndrome is characterized by an aberrant hairline (unilateral or bilateral wedge-shaped extension of the anterior hairline from the temple region to the ipsilateral eye) and anomalies of the eyes (widely spaced eyes, anophthalmia/microphthalmia and/or cryptophthalmos, colobomas of the upper eyelid, and corneopalpebral synechiae), nose (bifid or broad nasal tip), abdominal wall (omphalocele or umbilical hernia), and anus (stenosis and/or anterior displacement of the anal opening). The manifestations and degree of severity vary even among affected members of the same family. Growth and psychomotor development are normal. BNAR syndrome is characterized by a bifid or wide nasal tip, anorectal anomalies, and kidney malformations (e.g., renal agenesis, renal dysplasia). Typically, the eye manifestations of MOTA syndrome are absent. FREM1-related CAKUT has been reported in two boys from Macedonia with isolated CAKUT who had the same homozygous FREM1 pathogenic variants. The diagnosis of a FREM1 autosomal recessive disorder is established in a proband with biallelic pathogenic variants in FREM1 identified by molecular genetic testing. Treatment of manifestations: Intensive ocular lubrication to avoid exposure keratopathy before surgery is performed; release of synechiae between the eyelid and cornea; surgical intervention and/or prostheses for anophthalmia/microphthalmia and cryptophthalmos if warranted; supportive care for those with visual impairment. Rhinoplasty for notched ala nasi or bifid nose. Dilation for anal stenosis. Surgical closure of omphalocele; surgical or conservative management of umbilical hernia. Supportive treatment to preserve kidney function and electrolyte balance; dialysis and transplant if indicated in individuals with kidney failure. Psychosocial support and care coordination as needed. Surveillance: Assess kidney function in those with kidney disease with frequency per nephrologist; social work and family support at each visit. Phenotypes caused by biallelic FREM1 pathogenic variants – including MOTA syndrome, BNAR syndrome, and FREM1-related CAKUT – are inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a FREM1 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being a carrier, and a 25% chance of being unaffected and not a carrier. Once the FREM1 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal/preimplantation genetic testing are possible.