IllnessWaardenburg syndrome I-IV, differential diagnosis

NGS +

[Sanger]

Waardenburg Syndrome includes genetically determined hearing loss and pigmentation changes in hair, skin and eyes. Congenital hearing loss can occur in one or both ears, but most patients hear normally. There are four different types of Waardenburg Syndrome: types I and II have similar characteristics - only type I is associated with Telecanthus. In type II, hearing loss is more common. Type III (also known as Klein-Waardenburg syndrome) includes prominent upper limbs with hearing loss and pigmentary changes. Type IV (also known as Waardenburg-Shah syndrome) combines Waardenburg syndrome and Hirschsprung disease. The symptoms vary even among family members. Type I/III is caused by PAX3 mutations, type II by MITF or SNAI2 changes, type IV by SOX10, EDN3 or EDNRB mutations. Both autosomal dominant and recessive inheritance patterns are obvious with incomplete penetrance and variable expressivity. Rare is type IIA due to digenic inheritance via MITF and TYR gene mutations. Sporadic mutations occur mainly in Type I. The diagnostic sensitivity of DNA tests has not yet been sufficiently investigated. Therefore, an inconspicuous genetic finding does not mean a reliable exclusion of a suspected clinical diagnosis.

(Basic diagnostic genes: ###; additional genes: ###)

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1531/

https://rarediseases.org/rare-diseases/waardenburg-syndrome/

• PCWH: Periph. demyel. neuropathy, Centr. dysmyelination, Waardenburg syndrome, Hirschsprung disease
• Alias: Auditory-pigmentary syndrome
• Allelic: ABCD syndrome (EDNRB)
• Allelic: Albinism, oculocutaneous, type IA (TYR)
• Allelic: Albinism, oculocutaneous, type IB (TYR)
• Allelic: Bart-Pumphrey syndrome (GJB2)
• Allelic: COMMAD syndrome (MITF)
• Allelic: Central hypoventilation syndrome, congenital (EDN3)
• Allelic: Craniofacial-deafness-hand syndrome (PAX3)
• Allelic: Deafness, AD 69, unilateral or asymmetric (KITLG)
• Allelic: Gastrointestinal stromal tumor, familial (KITLG)
• Allelic: Hirschsprung disease, susceptibility to, 2 (EDNRB)
• Allelic: Hirschsprung disease, susceptibility to, 4 (EDN3)
• Allelic: Hyperpigmentation with/-out hypopigmentation (KITLG)
• Allelic: Hystrix-like ichthyosis with deafness (GJB2)
• Allelic: Mastocytosis, cutaneous (KIT)
• Allelic: Melanoma, cutaneous malignant, susceptibility to, 8 (MITF)
• Allelic: Melanoma, cutaneous malignant, susceptibility to, 8 (TYR)
• Allelic: Microphthalmia with limb anomalies (SMOC1)
• Allelic: PCWH syndrome (SOX10)
• Allelic: Piebaldism (KIT, SNAI2)
• Allelic: Rhabdomyosarcoma 2, alveolar (PAX3)
• Allelic: Skin/hair/eye pigmentation 3, blue/green eyes (TYR)
• Allelic: Skin/hair/eye pigmentation 3, light/dark/freckling skin (TYR)
• Allelic: Skin/hair/eye pigmentation 7, blond/brown hair (KITLG)
• Allelic: Tietz albinism-deafness syndrome (MITF)
• Mastocytosis, cutaneous (KITLG)
• Piebaldism (KITLG)
• Waardenburg syndrome, type 1 (PAX3)
• Waardenburg syndrome, type 2 [panelapp red] (MITF)
• Waardenburg syndrome, type 2A (MITF)
• Waardenburg syndrome, type 2D (SNAI2)
• Waardenburg syndrome, type 2E, with/-out neurologic involvement (SOX10)
• Waardenburg syndrome, type 2F (KITLG)
• Waardenburg syndrome, type 3 (PAX3)
• Waardenburg syndrome, type 4A (EDNRB)
• Waardenburg syndrome, type 4B (EDN3)
• Waardenburg syndrome, type 4C (SOX10)
• Waardenburg syndrome/albinism, digenic (TYR)
• Waardenburg syndrome/ocular albinism, digenic (MITF)