Case report A thirty-six year-old African man, born in the Southern part of Libya, presented with congenital deafness and a white forelock. He was noted to have variable-sized hypopigmented and depigmented patches. [ijdvl.com]

Features are present from birth. As it is a rare condition and clinical signs can be subtle, diagnosis may not be made until later in life. Four major clinical subtypes of Waardenburg syndrome have been identified. [dermnetnz.org]

Sensorineural hearing loss is present in the majority of people with WS2 (almost 80%), and heterochromia iridum (differences in eye coloring) is present in almost half.[1] Progressive hearing loss has also been reported in some people with WS2.[3] In [rarediseases.info.nih.gov]

April 16, 2019; 92 (16) Resident & Fellow Section First published April 15, 2019, DOI: https://doi.org/10.1212/WNL.0000000000007318 A 5-year-old boy presented with bilateral congenital sensorineural hearing loss and bilateral isohypochromia iridis without [n.neurology.org]

CASE REPORT A Turkish family presented with two of three sons showing clinical symptoms of WS type 2. [bjo.bmj.com]

• Epilepsy

  Ceroid lipofuscinosis, neuronal, 5 256731 CLN6 Ceroid lipofuscinosis, neuronal, 6 601780 CLN6 Ceroid lipofuscinosis, neuronal, Kufs type, adult onset, 204300 CLN8 Ceroid lipofuscinosis, neuronal, 8 600143 CLN8 Ceroid lipofuscinosis, neuronal, 8 Northern epilepsy [qgenomics.com]

• Flexion Contracture

  Type 3 Type 3 (Klein-Waardenburg syndrome) also has similar features to type 1 Waardenburg syndrome, but with musculoskeletal abnormalities, such as muscle hypoplasia, flexion contractures or syndactyly (fused digits). [dermnetnz.org]

  Bilateral defects may include underdevelopment (hypoplasia) and abnormal shortness of the upper limbs; abnormal bending of certain joints of the fingers in fixed positions (flexion contractures); fusion of wrist (carpal) bones; and/or webbing or fusion [rarediseases.org]

• Sweating

  Hydrolethalus syndrome 2 614120 KIZ Retinitis pigmentosa 69 615780 KLHL7 Cold induced sweating syndrome 3 617055 KLHL7 Retinitis pigmentosa 42 612943 KRT12 Meesmann corneal dystrophy, 122100 KRT3 Meesmann corneal dystrophy, 122100 LAMA1 Poretti-Boltshauser [qgenomics.com]

• Hyperpigmentation

  (Centre) Left: right fundus with an area of hypopigmentation on the posterior pole as well as nasally; pigmentary mottling and spots of hyperpigmentation in the temporal periphery (arrow); (right) left fundus, albinoid in type with spots of hyperpigmentation [bjo.bmj.com]

• Blue Eyes

  People with this condition often have very pale blue eyes or different colored eyes, such as one blue eye and one brown eye. Sometimes one eye has segments of two different colors. [medlineplus.gov]

  Complete heterochromia irides and especially the brilliant sapphire-blue eye colour have been noted rarely in non-Waardenburg people.2 Slit lamp examination of the left iris of the second son showed a thick iris of a brilliant blue colour without any [bjo.bmj.com]

  […] and hair Pigmentary abnormalities of the eyes, such as heterochromia iridis (differently coloured eyes), which may be complete, partial, or segmental; isohypochromia iridis (pale blue eyes); or abnormal pigmentation of the fundus Type 2 Type 2 has similar [dermnetnz.org]

  For example, the iris of one eye may be blue while the other has a different color or one or both irides may seem unusually “mottled” in appearance. [rarediseases.org]

• Esotropia

  Firstly, the 5 year old boy, the youngest of three children of a non-consanguineous couple, was referred for ophthalmological evaluation because of constant esotropia in the left eye. [bjo.bmj.com]

  (F) A 25 years old niece (IV:5) showed normal ocular and fundal examinations, however, a large angle esotropia OS secondary to dense amblyopia was observed. [journals.plos.org]

• Strabismus

  J Pediatr Ophthalmol Strabismus 1984;21:209–14. CAS PubMed Google Scholar [nature.com]

  He had bilateral dark brown irides and strabismus convergens in the left eye (Fig 1, top). The pattern of fundus pigmentation was of a distinctly abnormal type in both eyes. [bjo.bmj.com]

• Lacrimation

  In addition, the condition may be associated with unusually low (inferior) openings to the tear (lacrimal) ducts and an increased susceptibility to infections of the lacrimal sacs (dacryocystitis). [rarediseases.org]

• Hearing Impairment

  Sensorineural hearing loss is present in the majority of people with WS2 (almost 80%), and heterochromia iridum (differences in eye coloring) is present in almost half.[1] Progressive hearing loss has also been reported in some people with WS2.[3] In [rarediseases.info.nih.gov]

  Congenital sensorineural hearing impairment MedGen UID: 356101 •Concept ID: C1865866 • Congenital Abnormality A type of hearing impairment caused by an abnormal functionality of the cochlear nerve with congenital onset. [www-ncbi-nlm-nih-gov.ezproxy.u-pec.fr]

  Some affected individuals may also have hearing impairment due to abnormalities of the inner ear (sensorineural deafness). [rarediseases.org]

  All affected individuals have profound to mild hearing impairment (HI). W index was less than 1.95 mm for each affected individual, therefore, dystopia canthorum was considered as absent. This feature helped us in excluding WS type 1 (Fig 2). [journals.plos.org]

  Cataract 41 116400 WFS1 {Diabetes mellitus, noninsulin-dependent, association with}, 125853 WRN Werner syndrome, 277700 YAP1 Coloboma, ocular, 120433 YAP1 Coloboma, ocular, with or without hearing impairment, cleft lip/palate, and/or mental retardation [qgenomics.com]

• Hypertelorism

  Hypertelorism MedGen UID: 9373 •Concept ID: C0020534 • Finding A condition in which there is an abnormally increased distance between two organs or bodily parts; most often, this term is referring to an increased distance between the orbits (orbital hypertelorism [www-ncbi-nlm-nih-gov.ezproxy.u-pec.fr]

  Rarely, affected individuals also have widely spaced eyes (ocular hypertelorism). As mentioned previously, researchers have described different forms of WS based upon certain symptoms and specific genetic findings. [rarediseases.org]

• Nystagmus

  Families with WS2A may have the full spectrum of eye findings seen in X-linked ocular albinism I (300500) including decreased acuity, photophobia, nystagmus, translucent irides, hypermetropia, and albinotic fundi with foveal hypoplasia. [disorders.eyes.arizona.edu]

  1 congenital, X-linked, 310700 FRMD7 Nystagmus, infantile periodic alternating, X-linked, 310700 FTL Hyperferritinemia-cataract syndrome, 600886 FTL L-ferritin deficiency, dominant and recessive, 615604 FTL Neurodegeneration with brain iron accumulation [qgenomics.com]

• Ataxia

  248200 ABCA4 {Macular degeneration, age-related, 2}, 153800 ABCC6 Arterial calcification, generalized, of infancy, 2 614473 ABCC6 Pseudoxanthoma elasticum, 264800 ABCC6 Pseudoxanthoma elasticum, forme fruste, 177850 ABHD12 Polyneuropathy, hearing loss, ataxia [qgenomics.com]

  DE LEOPARD (3 GENES) NGS BRAF, PTPN11, RAF1 SÍNDROME DE MEDNIK NGS AP1S1 SÍNDROME DE MEGDHEL NGS SERAC1 SÍNDROME DE MOHR-TRANEBJAERG NGS TIMM8A SÍNDROME DE PERRAULT (4 GENES) NGS CLPP, HARS2, HSD17B4, LARS2 SÍNDROME PHARC (POLINEUROPATÍA-HIPOACUSIA-ATAXIA-RETINITIS [humv.es]

Treatment Treatment Options: No ocular treatment is necessary but assistive hearing devices can be helpful. [disorders.eyes.arizona.edu]

Treatment may include the use of hearing aids and/or cosmetic products or treatments (if desired) for skin hypopigmentation.[1] Waardenburg syndrome type 2 can be further divided into subtypes based on the genetic cause, when the responsible gene can [rarediseases.info.nih.gov]

Standard Therapies Treatment The treatment of WS is directed toward the specific symptoms that are apparent in each individual. [rarediseases.org]

What is the treatment for Waardenburg syndrome? There is no direct treatment for Waardenburg syndrome itself, and as it is a genetic condition there is no cure. Genetic counselling may be beneficial for affected patients who want to start a family. [dermnetnz.org]

As no treatment is available for patients with WS 2, prompt diagnosis and referral to a hearing specialist are crucial for the normal development of patients affected with this condition. [ijdvl.com]

PMID: 9192262Free PMC Article Prognosis Cesca F, Bettella E, Polli R, Cama E, Scimemi P, Santarelli R, Murgia A Int J Pediatr Otorhinolaryngol 2018 Jan;104:88-93. Epub 2017 Oct 31 doi: 10.1016/j.ijporl.2017.10.042. [www-ncbi-nlm-nih-gov.ezproxy.u-pec.fr]

PMID: 12180152Free PMC Article Etiology Li S, Guo M, Ruan B, Liu Y, Cui X, Han W, Li R Genet Test Mol Biomarkers 2020 May;24(5):249-255. Epub 2020 Apr 3 doi: 10.1089/gtmb.2019.0231. [www-ncbi-nlm-nih-gov.ezproxy.u-pec.fr]

These may include the use of specially tinted glasses or contact lenses (e.g., to help reduce possible sensitivity to light), measures to help prevent or treat infection, or other preventive or therapeutic steps. [rarediseases.org]