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Immunodeficiency 123 with HPV-related verrucosis(IMD123)

MedGen UID:
1855052
Concept ID:
C5935639
Disease or Syndrome
Synonyms: IMD123; IMMUNODEFICIENCY 123 WITH HPV-RELATED VERRUCOSIS
 
Gene (location): CD28 (2q33.2)
 
Monarch Initiative: MONDO:0971177
OMIM®: 620901

Definition

Immunodeficiency-123 with HPV-related verrucosis (IMD123) is an autosomal recessive immunologic disorder characterized by the onset of HPV-related common cutaneous warts in the first decade of life. The severity of the skin lesions appears to be related to the specific HPV subtype: infection with HPV2 may progress to severe generalized hyperkeratotic cutaneous papillomatosis with cutaneous horns ('tree-man' phenotype), whereas infection with HPV4 remains stable and may even regress with age. Affected individuals do not show susceptibility to other infections, and they do not show clinical manifestations even with CMV and EBV viremia. Peripheral blood leukocytes and immunoglobulins are essentially normal, but antibody response to vaccination is variably decreased and there is impaired T-cell function, particularly of CD4+ T cells. The findings are consistent with an exclusive and specific impairment of T-cell adaptive immunity with increased susceptibility to alpha- and gamma-HPV (et al., 2021). [from OMIM]

Clinical features

From HPO
Genital warts
MedGen UID:
40445
Concept ID:
C0009663
Disease or Syndrome
Warts affecting the skin in the genital area (penile shaft, scrotum, vagina, or labia majora). Warts can be small, beginning as a pinhead-size swelling that may become larger and take on a pedunculated appearance. Warts can spread and coalesce into large masses in the genital or anal area. Their color is variable but tends to be skin colored or darker, and they may occasionally bleed. Warts may cause itching, redness, or discomfort. An outbreak of genital warts may also cause psychological distress.
Verruca plana
MedGen UID:
547216
Concept ID:
C0276262
Disease or Syndrome
Slightly raised wart 2-5 mm in diameter often associated with viral infections, commonly persistent in immunodeficient individuals.
Verrucae
MedGen UID:
777120
Concept ID:
C3665596
Finding
Warts, benign growths on the skin or mucous membranes that cause cosmetic problems as well as pain and discomfort. Warts most often occur on the hands, feet, and genital areas.
Disseminated cutaneous warts
MedGen UID:
1708110
Concept ID:
C5139200
Neoplastic Process
Multiple skin warts located in multiple parts of the body, e.g., neck, trunks, and extremities.
Molluscum contagiosum
MedGen UID:
10081
Concept ID:
C0026393
Disease or Syndrome
Molluscum contagiosum is a cutaneous viral infection that is commonly observed in both healthy and immunocompromised children. The infection is caused by a member of the Poxviridae family, the molluscum contagiosum virus. Molluscum contagiosum presents as single or multiple small white or flesh-colored papules that typically have a central umbilication. The central umbilication may be difficult to observe in young children and, instead, may bear an appearance similar to an acneiform eruption. The lesions vary in size (from 1 mm to 1 cm in diameter) and are painless, although a subset of patients report pruritus in the area of infection. On average, 11-20 papules appear on the body during the course of infection and generally remains a self-limiting disease. However, in immunosuppressed patients, molluscum contagiosum can be a severe infection with hundreds of lesions developing on the body. Extensive eruption is indicative of an advanced immunodeficiency state.
Recurrent otitis media
MedGen UID:
155436
Concept ID:
C0747085
Disease or Syndrome
Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media.
Persistent EBV viremia
MedGen UID:
767466
Concept ID:
C3554552
Finding
Persistent presence of Epstein-Barr virus in the blood.
Persistent CMV viremia
MedGen UID:
1696514
Concept ID:
C5139221
Finding
Lasting (uncontrolled) presence of cytomegalovirus in the blood circulation.
Cutaneous horn
MedGen UID:
508356
Concept ID:
C0085664
Acquired Abnormality
A cutaneous horn is a keratinized non-malignant protrusion on the surface of the skin. Diagnosis is established by biopsy of the horn and biopsy of the horn and the underlying skin.

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