MedGen

Cataract is an opacification of the lens or lens capsule in the eye and is the most common cause of childhood blindness in the world, with an incidence of 1 to 3 per 10,000 live births. If untreated in infancy or childhood, it frequently causes visual impairment and can result in irreversible amblyopia. Nuclear cataract refers to opacification within the embryonal and/or fetal nuclei of the lens (summary by Berry et al., 2013). [from OMIM]

Any retinitis pigmentosa in which the cause of the disease is a mutation in the PROM1 gene. [from MONDO]

Immunodeficiency-41 is an autosomal recessive complex disorder of immune dysregulation. Affected individuals present in infancy with recurrent viral, fungal, and bacterial infections, lymphadenopathy, and variable autoimmune features, such as autoimmune enteropathy and eczematous skin lesions. Immunologic studies show a defect in T-cell regulation (summary by Goudy et al., 2013). [from OMIM]

Developmental and epileptic encephalopathy-41 (DEE41) is a neurologic disorder characterized by the onset of seizures in the first days or weeks of life. Affected infants show severely impaired psychomotor development with hypotonia, spasticity, lack of speech, poor visual fixation, feeding difficulties sometimes necessitating tube feeding, poor overall growth and microcephaly, and contractures. Brain imaging may show delayed myelination, thin corpus callosum, and cerebral atrophy (summary by the EPI4K Consortium, 2016). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350. [from OMIM]

Any non-syndromic X-linked intellectual disability in which the cause of the disease is a mutation in the GDI1 gene. [from MONDO]

Autosomal dominant deafness-41 (DFNA41) is characterized by onset of progressive sensorineural hearing loss usually in the second decade. The hearing loss is severe and ultimately affects all frequencies. Exposure to noise exacerbates the hearing loss, particularly at high frequencies (summary by Yan et al., 2013). [from OMIM]

Autosomal recessive intellectual developmental disorder-41 (MRT41) is characterized by macrocephaly and global developmental delay. Some patients have seizures (Baple et al., 2014). [from OMIM]

Any autosomal dominant non-syndromic intellectual disability in which the cause of the disease is a mutation in the TBL1XR1 gene. [from MONDO]

Immunodeficiency-67 (IMD67) is an autosomal recessive primary immunodeficiency characterized by recurrent severe systemic and invasive bacterial infections beginning in infancy or early childhood. The most common organisms implicated are Streptococcus pneumoniae and Staphylococcus aureus; Pseudomonas and atypical Mycobacteria may also be observed. IMD67 is life-threatening in infancy and early childhood. The first invasive infection typically occurs before 2 years of age, with meningitis representing up to 41% of the bacterial infections. The mortality rate in early childhood is high, with most deaths occurring before 8 years of age. Affected individuals have an impaired inflammatory response to infection, including lack of fever and neutropenia, although erythrocyte sedimentation rate (ESR) and C-reactive protein may be elevated. General immunologic workup tends to be normal, with normal levels of B cells, T cells, and NK cells. However, more detailed studies indicate impaired cytokine response to lipopolysaccharide (LPS) and IL1B (147720) stimulation; response to TNFA (191160) is usually normal. Patients have good antibody responses to most vaccinations, with the notable exception of pneumococcal vaccination. Viral, fungal, and parasitic infections are not generally observed. Early detection is critical in early childhood because prophylactic treatment with IVIg or certain antibiotics is effective; the disorder tends to improve naturally around adolescence. At the molecular level, the disorder results from impaired function of selective Toll receptor (see TLR4, 603030)/IL1R (see IL1R1, 147810) signaling pathways that ultimately activate NFKB (164011) to produce cytokines (summary by Ku et al., 2007; Picard et al., 2010; Grazioli et al., 2016). See also IMD68 (612260), caused by mutation in the MYD88 gene (602170), which shows a similar phenotype to IMD67. As the MYD88 and IRAK4 genes interact in the same intracellular signaling pathway, the clinical and cellular features are almost indistinguishable (summary by Picard et al., 2010). [from OMIM]

A rare autosomal dominant cerebellar ataxia type III disorder with characteristics of adult-onset progressive imbalance and loss of coordination associated with an ataxic gait. Mild atrophy of the cerebellar vermis has been reported on brain magnetic resonance imaging. [from SNOMEDCT_US]

Ciliary dyskinesia-41 (CILD41) is an autosomal recessive disorder characterized by chronic sinusitis, otitis media, and bronchiectasis (Bustamante-Marin et al., 2019). For a phenotypic description and a discussion of genetic heterogeneity of primary ciliary dyskinesia, see CILD1 (244400). [from OMIM]

Warburg Micro syndrome-1 (WARBM1) is a rare autosomal recessive syndrome characterized by microcephaly, microphthalmia, microcornea, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe mental retardation, spastic diplegia, and hypogonadism (summary by Morris-Rosendahl et al., 2010). Genetic Heterogeneity of Warburg Micro Syndrome Warburg Micro syndrome-2 (WARBM2; 614225) is caused by mutation in the RAB3GAP2 gene (609275) on chromosome 1q41. WARBM3 (614222) is caused by mutation in the RAB18 gene (602207) on chromosome 10p12. WARBM4 (615663) is caused by mutation in the TBC1D20 gene (611663) on chromosome 20p13. Handley et al. (2013) provided an overview of the disease variants identified in the RAB3GAP1, RAB3GAP2, and RAB18 genes, noting that a total of 144 families with WARBM and 9 families with Martsolf syndrome had been studied. Mutations were identified in RAB3GAP1 in 41% of cases, in RAB3GAP2 in 7% of cases, and in RAB18 in 5% of cases. Although RAB18 had not been linked to RAB3 pathways, Handley et al. (2013) stated that mutations in all 3 genes cause an indistinguishable phenotype, making it likely that there is some functional overlap. [from OMIM]

Spermatogenic failure-41 (SPGF41) is characterized by infertility due to multiple morphologic abnormalities of the flagella (MMAF). Patient semen analysis has also shown oligozoospermia, and the flagellar abnormalities include short, absent, coiled, and irregular-caliber flagella. Some sperm show tapered heads and acrosomal abnormalities (Beurois et al., 2019). For a discussion of genetic heterogeneity of spermatogenic failure, see SPGF1 (258150). [from OMIM]

The middle finger is more than 2 SD above the mean for newborns 27 to 41 weeks EGA or above the 97th centile for children from birth to 16 years of age AND the five digits retain their normal length proportions relative to each other (i.e., it is not the case that the middle finger is the only lengthened digit), or, Fingers that appear disproportionately long compared to the palm of the hand. [from HPO]

A pure form of hereditary spastic paraplegia with onset in adolescence or early adulthood of slowly progressive spastic paraplegia, proximal muscle weakness of the lower extremities and small hand muscles, hyperreflexia, spastic gait and mild urinary compromise. [from SNOMEDCT_US]