MedGen

Dyskeratosis congenita and related telomere biology disorders (DC/TBD) are caused by impaired telomere maintenance resulting in short or very short telomeres. The phenotypic spectrum of telomere biology disorders is broad and includes individuals with classic dyskeratosis congenita (DC) as well as those with very short telomeres and an isolated physical finding. Classic DC is characterized by a triad of dysplastic nails, lacy reticular pigmentation of the upper chest and/or neck, and oral leukoplakia, although this may not be present in all individuals. People with DC/TBD are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome or acute myelogenous leukemia, solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis. Other findings can include eye abnormalities (epiphora, blepharitis, sparse eyelashes, ectropion, entropion, trichiasis), taurodontism, liver disease, gastrointestinal telangiectasias, and avascular necrosis of the hips or shoulders. Although most persons with DC/TBD have normal psychomotor development and normal neurologic function, significant developmental delay is present in both forms; additional findings include cerebellar hypoplasia (Hoyeraal Hreidarsson syndrome) and bilateral exudative retinopathy and intracranial calcifications (Revesz syndrome and Coats plus syndrome). Onset and progression of manifestations of DC/TBD vary: at the mild end of the spectrum are those who have only minimal physical findings with normal bone marrow function, and at the severe end are those who have the diagnostic triad and early-onset BMF. [from GeneReviews]

Any sarcoidosis in which the cause of the disease is a mutation in the HLA-DRB1 gene. [from MONDO]

Dyskeratosis congenita and related telomere biology disorders (DC/TBD) are caused by impaired telomere maintenance resulting in short or very short telomeres. The phenotypic spectrum of telomere biology disorders is broad and includes individuals with classic dyskeratosis congenita (DC) as well as those with very short telomeres and an isolated physical finding. Classic DC is characterized by a triad of dysplastic nails, lacy reticular pigmentation of the upper chest and/or neck, and oral leukoplakia, although this may not be present in all individuals. People with DC/TBD are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome or acute myelogenous leukemia, solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis. Other findings can include eye abnormalities (epiphora, blepharitis, sparse eyelashes, ectropion, entropion, trichiasis), taurodontism, liver disease, gastrointestinal telangiectasias, and avascular necrosis of the hips or shoulders. Although most persons with DC/TBD have normal psychomotor development and normal neurologic function, significant developmental delay is present in both forms; additional findings include cerebellar hypoplasia (Hoyeraal Hreidarsson syndrome) and bilateral exudative retinopathy and intracranial calcifications (Revesz syndrome and Coats plus syndrome). Onset and progression of manifestations of DC/TBD vary: at the mild end of the spectrum are those who have only minimal physical findings with normal bone marrow function, and at the severe end are those who have the diagnostic triad and early-onset BMF. [from GeneReviews]

Dyskeratosis congenita and related telomere biology disorders (DC/TBD) are caused by impaired telomere maintenance resulting in short or very short telomeres. The phenotypic spectrum of telomere biology disorders is broad and includes individuals with classic dyskeratosis congenita (DC) as well as those with very short telomeres and an isolated physical finding. Classic DC is characterized by a triad of dysplastic nails, lacy reticular pigmentation of the upper chest and/or neck, and oral leukoplakia, although this may not be present in all individuals. People with DC/TBD are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome or acute myelogenous leukemia, solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis. Other findings can include eye abnormalities (epiphora, blepharitis, sparse eyelashes, ectropion, entropion, trichiasis), taurodontism, liver disease, gastrointestinal telangiectasias, and avascular necrosis of the hips or shoulders. Although most persons with DC/TBD have normal psychomotor development and normal neurologic function, significant developmental delay is present in both forms; additional findings include cerebellar hypoplasia (Hoyeraal Hreidarsson syndrome) and bilateral exudative retinopathy and intracranial calcifications (Revesz syndrome and Coats plus syndrome). Onset and progression of manifestations of DC/TBD vary: at the mild end of the spectrum are those who have only minimal physical findings with normal bone marrow function, and at the severe end are those who have the diagnostic triad and early-onset BMF. [from GeneReviews]

Dyskeratosis congenita and related telomere biology disorders (DC/TBD) are caused by impaired telomere maintenance resulting in short or very short telomeres. The phenotypic spectrum of telomere biology disorders is broad and includes individuals with classic dyskeratosis congenita (DC) as well as those with very short telomeres and an isolated physical finding. Classic DC is characterized by a triad of dysplastic nails, lacy reticular pigmentation of the upper chest and/or neck, and oral leukoplakia, although this may not be present in all individuals. People with DC/TBD are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome or acute myelogenous leukemia, solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis. Other findings can include eye abnormalities (epiphora, blepharitis, sparse eyelashes, ectropion, entropion, trichiasis), taurodontism, liver disease, gastrointestinal telangiectasias, and avascular necrosis of the hips or shoulders. Although most persons with DC/TBD have normal psychomotor development and normal neurologic function, significant developmental delay is present in both forms; additional findings include cerebellar hypoplasia (Hoyeraal Hreidarsson syndrome) and bilateral exudative retinopathy and intracranial calcifications (Revesz syndrome and Coats plus syndrome). Onset and progression of manifestations of DC/TBD vary: at the mild end of the spectrum are those who have only minimal physical findings with normal bone marrow function, and at the severe end are those who have the diagnostic triad and early-onset BMF. [from GeneReviews]

A posterior polymorphous corneal dystrophy that has material basis in autosomal dominant inheritance of mutation in the OVOL2 gene on chromosome 20p11.23. [from MONDO]

Cone-rod dystrophy-10 (CORD10) is characterized by progressive loss of visual acuity and color vision, followed by night blindness and loss of peripheral vision. Patients may experience photophobia and epiphora in bright light (Abid et al., 2006). Mutation in SEMA4A can also cause a form of retinitis pigmentosa (RP35; 610282). For a general phenotypic description and a discussion of genetic heterogeneity of cone-rod dystrophy, see 120970. [from OMIM]

Epithelial recurrent erosion dystrophy (ERED) is characterized by frequent painful recurrent corneal erosions, with onset in the first decade of life and subsequent gradual decrease in frequency, with cessation in the third or fourth decade. Small gray anterior stromal flecks associated with larger focal gray-white disc-shaped, circular, or wreath-like lesions with central clarity, in the Bowman layer and immediately subjacent anterior stroma, varying from 0.2 to 1.5 mm in diameter, appear to be clinically diagnostic of ERED (Oliver et al., 2016). [from OMIM]

Meesmann corneal dystrophy-2 (MECD2) is characterized by fragility of the anterior corneal epithelium and the presence of intraepithelial microcysts. Although the disease is generally mild and affected individuals are often asymptomatic, some suffer from recurrent erosions leading to lacrimation, photophobia, and deterioration in visual acuity (summary by Szaflik et al., 2008). For a discussion of genetic heterogeneity of Meesmann corneal dystrophy, see MECD1 (122100). [from OMIM]

Keratoendotheliitis fugax hereditaria (KEFH) is an autosomal dominant corneal disease that periodically and fleetingly affects the corneal endothelium, stroma, and vision, eventually resulting in central corneal stromal opacities in some patients. The disease is characterized by episodes of unilateral ocular pain, pericorneal injection, and photophobia. The acute symptoms vanish in 1 to 2 days, but vision remains blurry for several weeks. Onset occurs between ages 3 and 12 years, and may involve either eye. Episodes generally decrease in frequency and become more mild with age (summary by Turunen et al., 2018). [from OMIM]

Congenital nasolacrimal drainage system impatency is relatively common, occurring in approximately 20% of children within the first year of life. Such infants typically manifest persistent epiphora and/or recurrent infections of the lacrimal pathway such as conjunctivitis. The most frequent site of such obstruction occurs at the distal intranasal segment of the nasolacrimal drainage system at the valve of Hasner (summary by Wang and Cunningham, 2011). Congenital dacryocystocele, an uncommon variant of nasolacrimal duct obstruction, characterized by the appearance of a cystic blue mass over the area of the lacrimal duct soon after birth. Dacryocystoceles are thought to result from a persistent membrane at the valve of Hasner and a functional obstruction of the common canaliculus or valve of Rosenmuller. The resulting lacrimal sac distention has been reported to be more common in female and non-Hispanic white patients, and familial cases have been described only sporadically. Common presenting signs include dacryocystitis, facial cellulitis, and respiratory distress; the development of astigmatism in association with dacryocystocele has only rarely been observed (summary by Shekunov et al., 2010). [from OMIM]

Hyperostosis cranialis interna (HCIN) is a bone disorder characterized by endosteal hyperostosis and osteosclerosis of the calvaria and the skull base. The progressive bone overgrowth causes entrapment and dysfunction of cranial nerves I, II, V, VII, and VIII (Waterval et al., 2010). [from OMIM]

Hereditary mucoepithelial dysplasia (HMD) is a rare autosomal dominant genodermatosis characterized by onset in infancy of a panepithelial defect involving the oral, nasal, conjunctival, vaginal, cervical, perineal, urethral, and bladder mucosa. Patients develop cataracts, blindness, nonscarring alopecia, perineal psoriasiform lesions, and follicular keratoses (Witkop et al., 1982). Although 1 family was reported to have progressive severe interstitial lung disease (Witkop et al., 1979), this feature has not been reported in other families and is not considered a criterion for diagnosis. However, the clinical triad of nonscarring alopecia, well-demarcated fiery red mucosa, and psoriasiform perineal involvement has been consistently observed (review by Boralevi et al., 2005). [from OMIM]

Nasopalpebral lipoma-coloboma syndrome (NPLCS) is an autosomal dominant condition characterized by upper eyelid and nasopalpebral lipomas, colobomas of upper and lower eyelids, telecanthus, and maxillary hypoplasia (summary by Suresh et al., 2011). [from OMIM]

Keratosis pilaris atrophicans (KPA) represents a group of rare genodermatoses characterized by perifollicular keratosis and inflammation that progresses to atrophy and scarring of the facial skin. Keratosis pilaris of extensor surfaces of limbs is a common associated finding. Affected individuals may present with features that overlap between 3 subtypes, keratosis pilaris atrophicans faciei (KPAF), keratosis follicularis spinulosa decalvans (KFSD), and atrophoderma vermiculata (AVA; see 209700) (summary by Klar et al., 2015). [from OMIM]

A cone-rod dystrophy that has material basis in variation in the chromosome region 1q12-q24. [from MONDO]

Digenic dyskeratosis congenita (DKCD) is characterized clinically by a combination of mucocutaneous features including abnormal skin pigmentation, nail dystrophy, thin hair, and oral leukoplakia. Some patients may have evidence of bone marrow failure, manifest as immune defects such as recurrent infections or hypogammaglobulinemia. Telomeres are shortened in patient cells. Individuals with DKCD may show severe adverse reactions to treatment with 5-FU (Tummala et al., 2022). For a discussion of genetic heterogeneity of dyskeratosis congenita, see DKCA1 (127550). [from OMIM]

Abnormally increased lacrimation, that is, excessive tearing (watering eye). [from HPO]