MedGen

In Alport syndrome (AS) a spectrum of phenotypes ranging from progressive renal disease with extrarenal abnormalities to isolated hematuria with a non-progressive or very slowly progressive course is observed. Approximately two thirds of AS is X-linked (XLAS); approximately 15% is autosomal recessive (ARAS), and approximately 20% is autosomal dominant (ADAS). In the absence of treatment, renal disease progresses from microscopic hematuria (microhematuria) to proteinuria, progressive renal insufficiency, and end-stage renal disease (ESRD) in all males with XLAS, and in all males and females with ARAS. Progressive sensorineural hearing loss (SNHL) is usually present by late childhood or early adolescence. Ocular findings include anterior lenticonus (which is virtually pathognomonic), maculopathy (whitish or yellowish flecks or granulations in the perimacular region), corneal endothelial vesicles (posterior polymorphous dystrophy), and recurrent corneal erosion. In individuals with ADAS, ESRD is frequently delayed until later adulthood, SNHL is relatively late in onset, and ocular involvement is rare. [from GeneReviews]

Noonan syndrome (NS) is characterized by characteristic facies, short stature, congenital heart defect, and developmental delay of variable degree. Other findings can include broad or webbed neck, unusual chest shape with superior pectus carinatum and inferior pectus excavatum, cryptorchidism, varied coagulation defects, lymphatic dysplasias, and ocular abnormalities. Although birth length is usually normal, final adult height approaches the lower limit of normal. Congenital heart disease occurs in 50%-80% of individuals. Pulmonary valve stenosis, often with dysplasia, is the most common heart defect and is found in 20%-50% of individuals. Hypertrophic cardiomyopathy, found in 20%-30% of individuals, may be present at birth or develop in infancy or childhood. Other structural defects include atrial and ventricular septal defects, branch pulmonary artery stenosis, and tetralogy of Fallot. Up to one fourth of affected individuals have mild intellectual disability, and language impairments in general are more common in NS than in the general population. [from GeneReviews]

Male EBP disorder with neurologic defects (MEND) is an X-linked recessive disorder representing a continuous phenotypic spectrum with variable manifestations associated with a defect in sterol biosynthesis. Features include intellectual disability, short stature, scoliosis, digital abnormalities, cataracts, and dermatologic abnormalities. Not all patients show all features, and the severity is highly variable. Molecular studies indicate that affected males are hemizygous for a nonmosaic hypomorphic EBP allele. Carrier females are generally clinically asymptomatic, but may show biochemical abnormalities (summary by Arnold et al., 2012 and Barboza-Cerda et al., 2014). [from OMIM]

Congenital cataracts cause 10 to 30% of all blindness in children, with one-third of cases estimated to have a genetic cause (summary by Bu et al., 2002). Mutations in the HSF4 gene have been found to cause multiple types of cataract, which have been described as infantile, lamellar, zonular, nuclear, anterior polar, stellate, and Marner-type. The preferred title for this entry was formerly 'Lamellar Cataract,' with 'Cataract, Marner Type; CAM; CTM' an included title. [from OMIM]

EDICT syndrome is an autosomal dominant syndromal anterior segment dysgenesis characterized by endothelial dystrophy, iris hypoplasia, congenital cataract, and thinning of the corneal stroma (Iliff et al., 2012). Syndromes with overlapping features have been reported, including cornea guttata with anterior polar cataracts (121390) and congenital corneal opacities, cornea guttata, and corectopia (608484). [from OMIM]

Mutations in the CRYGB gene have been found to cause multiple types of cataract, which have been described as lamellar, anterior polar, and complete. [from OMIM]

Developmental delay with or without intellectual impairment or behavioral abnormalities (DDIB) is an autosomal dominant disorder with a nonspecific phenotype of developmental delay. Additional features may include neonatal feeding problems, hypotonia, and dysmorphic facial features (Dulovic-Mahlow et al., 2019; van Woerden et al., 2021). [from OMIM]

A cataract that has material basis in mutation in the region 14q22-q23. [from MONDO]

Anterior polar cataracts are small opacities on the anterior surface of the lens. They usually do not interfere with vision (Moross et al., 1984). The preferred title/symbol of this entry was formerly 'Cataract, Anterior Polar, 2; CTAA2.' [from OMIM]

Metaphyseal dysostosis-intellectual disability-conductive deafness syndrome is characterised by metaphyseal dysplasia, short-limb dwarfism, mild intellectual deficit and conductive hearing loss, associated with repeated episodes of otitis media in childhood. It has been described in three brothers born to consanguineous Sicilian parents. Variable manifestations included hyperopia and strabismus. The mode of inheritance is autosomal recessive. [from ORDO]

Xerosis and growth failure with immune and pulmonary dysfunction syndrome (XGIP) is characterized by premature birth, intrauterine and postnatal growth retardation, and collodion membrane or collodion-like skin at birth with dry skin thereafter. Patients also exhibit bronchopulmonary disease and thrombocytopenia and neutropenia. Variable features include cardiac anomalies, seizures, encephalopathy, and cholestasis, and cataract has been observed. Affected individuals die within the first year of life (Shamseldin et al., 2023). [from OMIM]

Neurofacioskeletal syndrome with or without renal agenesis (NFSRA) is characterized by developmental delay and/or intellectual disability; corpus callosum hypoplasia or agenesis; facial dysmorphism, including upslanting palpebral fissures, broad nasal tip, and wide mouth; and skeletal abnormalities, including short stature, scoliosis, and flexion contractures, with broad fingertips and/or toes. Renal agenesis, unilateral or bilateral, has also been observed in some patients (Schneeberger et al., 2020). [from OMIM]

A polar cataract that affects the anterior pole of the lens. [from HPO]