MedGen

Intellectual developmental disorder-29 (XLID29) is a nonspecific form of XLID. It is part of a phenotypic spectrum of disorders caused by mutation in the ARX gene comprising a nearly continuous series of developmental disorders ranging from lissencephaly (LISX2; 300215) to Proud syndrome (300004) to infantile spasms without brain malformations (DEE1; 308350) to Partington syndrome (309510) (Kato et al., 2004; Wallerstein et al., 2008). [from OMIM]

Spastic paraplegia 4 (SPG4; also known as SPAST-HSP) is characterized by insidiously progressive bilateral lower-limb gait spasticity. More than 50% of affected individuals have some weakness in the legs and impaired vibration sense at the ankles. Sphincter disturbances are very common. Onset is insidious, mostly in young adulthood, although symptoms may start as early as age one year and as late as age 76 years. Intrafamilial variation is considerable. [from GeneReviews]

Any retinitis pigmentosa in which the cause of the disease is a mutation in the POMGNT1 gene. [from MONDO]

Spastic paraplegia-76 is an autosomal recessive neurologic disorder characterized by young-adult onset of slowly progressive spasticity of the lower limbs resulting in gait difficulties. Most affected individuals have upper limb involvement and additional features such as foot deformities and dysarthria. Cognition is unaffected (summary by Gan-Or et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see SPG5A (270800). [from OMIM]

Any autosomal recessive nonsyndromic deafness in which the cause of the disease is a mutation in the SYNE4 gene. [from MONDO]

Immunodeficiency-76 (IMD76) is an autosomal recessive primary immunologic disorder characterized by onset of recurrent bacterial, viral, and fungal infections in early childhood. Laboratory studies show T-cell lymphopenia and may show variable B-cell or immunoglobulin abnormalities. More variable features found in some patients include lymphoma and neurologic features. Although bone marrow transplantation may be curative, many patients die in childhood (summary by Lyszkiewicz et al., 2020). [from OMIM]

Developmental and epileptic encephalopathy-76 (DEE76) is an autosomal recessive neurodevelopmental disorder characterized by early-onset, usually refractory, seizures, severely delayed global development, hypotonia, peripheral spasticity, and abnormalities on brain imaging, mainly cerebral atrophy and delayed myelination. Some patients may have additional features, such as scoliosis or microcephaly. The disorder may result in death in childhood (summary by Bell et al., 2019). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350. [from OMIM]

Hydrops fetalis is a descriptive term for generalized edema of the fetus, with fluid accumulation in extravascular components and body cavities. It is not a diagnosis in itself, but a symptom and end-stage result of a wide variety of disorders. In the case of immune hydrops fetalis, a frequent cause is maternofetal incompatibility as in that related to a number of genetic anemias and metabolic disorders expressed in the fetus; in other instances, it remains idiopathic and likely multifactorial (summary by Bellini et al., 2009). Nonimmune hydrops fetalis accounts for 76 to 87% of all described cases of hydrops fetalis (Bellini et al., 2009). Genetic Heterogeneity of Hydrops Fetalis In southeast Asia, alpha-thalassemia (604131) is the most common cause of hydrops fetalis, accounting for 60 to 90% of cases. Almost all of these cases result from homozygous deletion of the HBA1 (141800) and HBA2 (141850) genes. A few cases have been reported that had 1 apparently normal alpha-globin gene, termed the hemoglobin H (613978) hydrops fetalis syndrome (summary by Chui and Waye, 1998). Other genetic disorders predisposing to NIHF include other congenital anemias, such as erythropoietic porphyria (e.g., 606938.0013), and many metabolic disorders, such as one form of Gaucher disease (e.g., 606463.0009), infantile sialic acid storage disease (269920), mucopolysaccharidosis type VII (253220), glycogen storage disease IV (232500), congenital disorder of glycosylation type Ia (212065), and disorders of lymphatic malformation (see, e.g., LMPHM1, 153100). [from OMIM]

Autosomal dominant deafness-76 (DFNA76) is characterized by progressive or nonprogressive hearing loss with variable age at onset. Hearing loss is more severe at higher frequencies in most patients (Schrauwen et al., 2019; Morgan et al., 2019; Diaz-Horta et al., 2019). [from OMIM]

Autosomal recessive intellectual developmental disorder-76 (MRT76) is characterized by impaired intellectual development, absent speech, poor sleep, abnormal EEG with seizures, normal brain imaging, and precocious puberty (Ismail et al., 2022). [from OMIM]

An abnormality of skull shape characterized by a increased anterior-posterior diameter, i.e., an increased antero-posterior dimension of the skull. Cephalic index less than 76%. Alternatively, an apparently increased antero-posterior length of the head compared to width. Often due to premature closure of the sagittal suture. [from HPO]

Spermatogenic failure-76 (SPGF76) is characterized by male infertility due to oligoasthenoteratozoospermia. Multiple morphologic abnormalities of the flagella (MMAF) have been observed, including short, absent, and irregular caliber flagella. Ultrastructural anomalies include disordered outer dense fibers and abnormal 9+2 microtubular structures (Cong et al., 2022). For a general phenotypic description and discussion of genetic heterogeneity of spermatogenic failure, see SPGF1 (258150). [from OMIM]