MedGen

Any retinitis pigmentosa in which the cause of the disease is a mutation in the ZNF513 gene. [from MONDO]

EXOSC3 pontocerebellar hypoplasia (EXOSC3-PCH) is characterized by abnormalities in the posterior fossa and degeneration of the anterior horn cells. At birth, skeletal muscle weakness manifests as hypotonia (sometimes with congenital joint contractures) and poor feeding. In persons with prolonged survival, spasticity, dystonia, and seizures become evident. Within the first year of life respiratory insufficiency and swallowing difficulties are common. Intellectual disability is severe. Life expectancy ranges from a few weeks to adolescence. To date, 82 individuals (from 58 families) with EXOSC3-PCH have been described. [from GeneReviews]

Any non-syndromic X-linked intellectual disability in which the cause of the disease is a mutation in the TSPAN7 gene. [from MONDO]

Immunodeficiency-58 is an autosomal recessive primary immunologic disorder characterized by early-onset skin lesions, including eczematous dermatitis, infectious abscesses, and warts, recurrent respiratory infections or allergies, and chronic persistent infections with candida, Molluscum contagiosum, mycobacteria, EBV, bacteria, and viruses. Some patients may have gastrointestinal involvement, including inflammatory bowel disease, EBV+ smooth muscle tumors, and esophagitis. Immunologic analysis shows defective T-cell function with decreased Treg cells and deficient CD3/CD28 costimulation responses in both CD4+ and CD8+ T cells. B-cell function may also be impaired (summary by Wang et al., 2016 and Alazami et al., 2018). [from OMIM]

Premature fusion of the various sutures in the human neurocranium (skull vault and base) is defined as craniosynostosis (CRS). Clinical consequences include abnormal head shape and increased intracranial pressure, which may result in neurologic symptoms, developmental delay, and hearing or vision problems. Approximately 80% of cases are classified as nonsyndromic craniosynostosis and present as isolated suture fusion with no other associated anomalies. Sagittal suture fusion is the most common form of isolated craniosynostosis, accounting for 40 to 58% of all isolated cases (summary by Yagnik et al., 2012). For a discussion of genetic heterogeneity of craniosynostosis, see CRS1 (123100). [from OMIM]

Developmental and epileptic encephalopathy-58 (DEE58) is a severe neurodevelopmental disorder characterized by the onset of infantile spasms and refractory seizures in the first days or months of life. Affected individuals have global developmental delay with impaired intellectual development, usually with absent speech and inability to walk. Additional features include optic atrophy with poor or absent visual fixation, hypotonia, feeding difficulties, and spasticity (summary by Hamdan et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350. [from OMIM]

Any autosomal recessive non-syndromic intellectual disability in which the cause of the disease is a mutation in the ELP2 gene. [from MONDO]

Autosomal dominant deafness-58 (DFNA58) is characterized by postlingual sensorineural deafness, with tinnitus and vestibular dysfunction additionally present in some patients (summary by Lezirovitz et al., 2020). [from OMIM]

Spermatogenic failure-58 (SPGF58) is characterized by male infertility due to multiple morphologic abnormalities of the flagella (MMAF). Sperm are immotile or show severely reduced progressive motility due to short and irregular caliber flagella as well as bent, coiled, and absent flagella. Head abnormalities have also been observed, including acrosomal and postacrosomal defects (Lores et al., 2021). For a general phenotypic description and discussion of genetic heterogeneity of spermatogenic failure, see SPGF1 (258150). [from OMIM]

Combined oxidative phosphorylation deficiency-58 (COXPD58) is an autosomal recessive disorder characterized by a wide range of clinical presentations including neonatal lactic acidosis, epileptic encephalopathy, developmental delay and impaired intellectual development with nonspecific changes on brain MRI, or mitochondrial myopathy with a treatable neuromuscular transmission defect (Van Haute et al., 2023). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060). [from OMIM]

Auriculocondylar syndrome-1 (ARCND1) is an autosomal dominant disorder of the first and second pharyngeal arches and is characterized by malformed ears (question mark ears), prominent cheeks, microstomia, abnormal temporomandibular joint, and mandibular condyle hypoplasia (summary by Masotti et al., 2008). Genetic Heterogeneity of Auriculocondylar Syndrome See also ARCND2A (614669) and ARCND2B (620458), caused by heterozygous or biallelic mutation, respectively, in the PLCB4 gene (600810) on chromosome 20p12; ARCND3 (615706), caused by mutation in the EDN1 gene (131240) on chromosome 6p24; and ARCND4 (620457), caused by mutation the HDAC9 gene (606543) on chromosome 7p21. See also 612798 for isolated question mark ears. Reviews Kokitsu-Nakata et al. (2012) tabulated clinical findings in 24 reported cases of auriculocondylar syndrome. The most common clinical signs observed were ear constriction (100%), abnormal temporomandibular joint (100%), mandibular condyle abnormality (93%), malocclusion (93%), round face (78%), microstomia (78%), micrognathia (78%), prominent cheeks (74%), hearing loss (56%), abnormal palate (55%), and crowded teeth (50%). The authors noted that the phenotype was highly variable in severity, even within families. Liu et al. (2021) reviewed 19 published cases of ARCND1 and tabulated the common features, including micrognathia (79%), auricular malformation (68%), microstomia (67%), prominent cheeks (63%), mandibular hypoplasia (58%), and round face (58%). Asymmetry of mandibular and auricular malformations was present in 4 patients, and the lesions were either more severe on the right or only the right side was affected, suggesting a predilection for right-sided deformities. The authors also noted that severe cases mostly occurred in female patients. Prenatal findings were available in 3 patients, and all showed polyhydramnios, with 2 having micrognathia evident on ultrasonography. The authors suggested that severe micrognathia and mandibular hypoplasia accompanied by polyhydramnios might be prenatal indicators of ARCND. Using a standardized questionnaire sent to referring physicians, Vegas et al. (2022) collected clinical data on 39 patients from 27 families with auriculocondylar syndrome and mutation in the GNAI3, PLCB4, or EDN1 genes. PLCB4 was the most common gene associated with ARCND, being mutated in 16 (59%) of the 27 families. Incomplete penetrance and/or variable expression was observed within families. [from OMIM]

Autosomal recessive spastic ataxia-2 (SPAX2) is a neurologic disorder characterized by onset in the first 2 decades of cerebellar ataxia, dysarthria, and variable spasticity of the lower limbs. Cognition is not affected (summary by Dor et al., 2014). For a discussion of genetic heterogeneity of spastic ataxia, see SPAX1 (108600). [from OMIM]