In this episode, we explore Sjögren’s disease (SD), a chronic autoimmune condition characterised primarily by severe dry eyes and dry mouth (sicca). Its pathogenesis involves genetic susceptibility (e.g., HLA-DRB1*03) and unchecked B-cell hyperactivity, driven by factors like BAFF and APRIL. Diagnosis relies on strict criteria, demanding evidence of specific autoantibodies (Anti-SSA/Ro or Anti-SSB/La) or characteristic lymphocytic infiltration in a gland biopsy (focus score ≥ 1). SD is a systemic disease, and patients face a significantly elevated risk of B-cell Non-Hodgkin Lymphoma (NHL) (5–10% lifetime risk), predicted by signs like permanent salivary gland swelling and low C4 complement levels. Current treatment focuses on symptomatic relief, with hydroxychloroquine often recommended first-line for inflammatory pain, while TNF-alpha inhibitors are strongly discouraged for sicca symptoms.

ORPHA:289390

Classification level: Disorder

• Primary Sjögren syndrome
• Primary SjD

Source: PubMed ID 28613703 38331820 25387476

Prevalence: 1-5 / 10 000

Inheritance: Not applicable

Age of onset: Adult

ICD-10: M35.0 

ICD-11: 4A43.20

OMIM: 270150

UMLS: C0151449 

GARD: 10252

Synonym(s): 

In this episode, we delve into Congenital Bilateral Absence of the Vas Deferens (CBAVD), a form of obstructive azoospermia and a key cause of male infertility frequently linked to CFTR gene mutations. We examine the lack of consensus among reproductive urologists regarding their preferred sperm extraction techniques (testicular or epididymal) for men with CBAVD/Cystic Fibrosis (CF). Finally, we stress the critical importance of genetic counseling for these patients and their partners to manage the risk of passing on CFTR mutations to their children when using assisted reproductive technology.

ORPHA:48

Classification level: Disorder

• Congenital bilateral agenesis of vas deferens
• Congenital bilateral aplasia of vas deferens

Prevalence: 1-5 / 10 000

Inheritance: Multigenic/multifactorial

Age of onset: Adolescent, Adult

ICD-10: Q55.4 

ICD-11: LB57

OMIM: 277180 300985

UMLS: C0403814 

MeSH: C535984 

GARD: 5461

MedDRA: 10010670

Synonym(s): 

Iniencephaly (IE) is an extremely rare, lethal neural tube defect. It is defined by a triad of severe malformations: a defect in the occipital bone, spinal dysraphism/short neck, and fixed retroflexion of the head. IE is categorized as apertus (with an encephalocele) or clausus (without). Given the invariably poor prognosis, early prenatal diagnosis using ultrasonography and MRI is crucial for clinical decision-making.

ORPHA:63259

Classification level: Disorder

Prevalence: Unknown

Inheritance: Multigenic/multifactorial, Not applicable

Age of onset: Infancy, Neonatal

ICD-10: Q00.2 

ICD-11: LA00.1

UMLS: C0152234 

GARD: 10506

MedDRA: 10022034

In this episode, we uncover 47,XYY syndrome, also known as Jacobs syndrome. Learn how early, sensationalized studies incorrectly linked the extra Y chromosome to aggression, creating the myth of the "criminal chromosome". We reveal what modern research actually shows: a condition often undiagnosed, associated primarily with tall stature and increased risks for learning disabilities and ADHD.

ORPHA:8

Classification level: Disorder

• Jacobs syndrome
• Double Y syndrome
• XYY syndrome
• Y disomy

Source: PubMed ID 1476413 23810129 32491631

Prevalence: 1-5 / 10 000

Inheritance: Not applicable

Age of onset: All ages

ICD-10: Q98.5 

ICD-11: LD52.1

UMLS: C3266843 

MeSH: C535317 

GARD: 5674

MedDRA: 10056894

In this episode, we explore unilateral renal agenesis — a rare congenital condition where one kidney fails to develop. Often discovered incidentally, it may occur alone or as part of a syndrome. Most people live healthy lives with one functioning kidney, though long-term follow-up is advised to monitor for hypertension, proteinuria, or renal impairment. We also touch on prenatal detection, genetic background, and key aspects of lifelong management.

ORPHA:93100

Classification level: Subtype of disorder

Prevalence: Unknown

Inheritance: Autosomal dominant

Age of onset: All ages, Antenatal

ICD-10: Q60.0 

ICD-11: LB30.00

OMIM: 617805

UMLS: C0266294 

MedDRA: 10053624

In this episode, we dive into prolactinoma, a typically benign tumor of the anterior pituitary that causes elevated prolactin and disrupts reproductive hormones. Clinical signs differ by sex: women often present with amenorrhea, infertility, or galactorrhea, while men may have impotence, reduced libido, and infertility. Diagnosis hinges on measuring prolactin levels and imaging the pituitary; treatment usually involves dopamine agonists, with surgery reserved for resistant or large tumors.

ORPHA:2965

Classification level: Disorder

• Lactotroph adenoma
• PRL-secreting pituitary adenoma
• PRLoma
• Pituitary lactotrophic adenoma
• Prolactin-secreting pituitary adenoma

Prevalence: 1-5 / 10 000

Inheritance: Autosomal dominant

Age of onset: Adolescent, Adult, Childhood, Elderly

ICD-10: D35.2 

ICD-11: 2F37.Y XH1QS0

UMLS: C0033375 

MeSH: D015175 

GARD: 4508

MedDRA: 10036832

In this episode, we explain FNAIT, a rare hematological disorder in which a mother’s immune system attacks fetal platelets inherited from the father. Infants present with thrombocytopenia at birth and may suffer bleeding, petechiae, purpura, or intracranial hemorrhage. We cover diagnosis, management, and current research efforts.

ORPHA:853

Classification level: Disorder

• FNAIT
• NAIT

Source: PubMed ID 30828796 36368687 36239096

Prevalence: 1-5 / 10 000

Inheritance: Not applicable

Age of onset: Antenatal, Neonatal

ICD-10: P61.0 

ICD-11: 3B64.00

UMLS: C3854603 

GARD: 2295

In this episode, we explore cleft palate — a congenital condition where the roof of the mouth doesn’t close completely during development. This opening can affect feeding, speech, hearing, and facial growth. We’ll look at how early surgical repair, speech therapy, and long-term multidisciplinary care can dramatically improve outcomes. Beyond the physical challenges, we’ll also touch on the emotional and social impact for children and families, and how modern treatment teams support both healing and confidence. Join us as we uncover the science, treatment, and human stories behind one of the most common craniofacial anomalies.

ORPHA:2014

Classification level: Group of disorders

Prevalence: 1-5 / 10 000

Inheritance: Multigenic/multifactorial, Not applicable

Age of onset: Antenatal, Neonatal

ICD-10: Q35 

ICD-11: LA42

OMIM: 119540

UMLS: C0008925 

MeSH: D002972 

GARD: 1896

MedDRA: 10009269

This episode explores Down syndrome from prevalence and causes to lifelong care. We discuss key clinical features, diagnostic methods, and genetic counseling, along with the importance of early therapy, education, and medical follow-up. Advances in care have greatly improved quality of life, and today the median life expectancy exceeds 60 years in developed countries.

ORPHA:870

Classification level: Disorder

• Trisomy 21

Source: PubMed ID 33130823 36692980 12699967

Prevalence: 1-5 / 10 000

Inheritance: Not applicable

Age of onset: Antenatal, Neonatal

ICD-10: Q90.0 , Q90.1 , Q90.2 , Q90.9 

ICD-11: LD40.0

OMIM: 190685

UMLS: C0013080 

MeSH: D004314 

GARD: 10247

MedDRA: 10044688