MedGen

Autosomal recessive deafness-49 (DFNB49) is characterized by prelingual profound sensorineural hearing loss at all frequencies (Riazuddin et al., 2006 and Chishti et al., 2008). [from OMIM]

CLCN4-related neurodevelopmental disorder (CLCN4-NDD), an X-linked disorder, is characterized in the 36 males reported to date by developmental delay or intellectual disability, behavioral/mental health issues (e.g., autism spectrum disorder, anxiety, hyperactivity, and bipolar disorder), epilepsy, and gastrointestinal dysfunction. The five heterozygous females with a de novo CLCN4 variant reported to date had findings very similar to those of affected males. Twenty-two of 25 heterozygous females identified in family studies following identification of an affected male were unaffected or had only mild specific learning difficulties and/or mental health concerns, whereas three were more severely affected. [from GeneReviews]

TECPR2-related hereditary sensory and autonomic neuropathy with intellectual disability (TECPR2-HSAN with ID) is characterized by developmental delay and subsequent intellectual disability, behavioral abnormalities, neurologic manifestations (muscular hypotonia, sensory neuropathy with lower-limb hypo- or areflexia and ataxic gait), and autonomic dysfunction (including central hypoventilation and apnea, gastrointestinal dysmotility, dysphagia, and gastroesophageal reflux disease with recurrent aspiration). To date, more than 30 individuals with TECPR2-HSAN with ID have been identified. [from GeneReviews]

Retinitis pigmentosa-49 (RP49) is characterized by onset of night blindness in childhood, followed by progressive loss of visual fields and reduced visual acuity. Typical fundus features are present, including pale optic disc, attenuated vasculature, and pigment deposits in the midperiphery (Zhang et al., 2004; Katagiri et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000. [from OMIM]

The spectrum of DCTN1-related neurodegeneration includes Perry syndrome, distal hereditary motor neuronopathy type 7B (dHMN7B), frontotemporal dementia (FTD), motor neuron disease / amyotrophic lateral sclerosis (ALS), and progressive supranuclear palsy. Some individuals present with overlapping phenotypes (e.g., FTD-ALS, Perry syndrome-dHMN7B). Perry syndrome (the most common of the phenotypes associated with DCTN1) is characterized by parkinsonism, neuropsychiatric symptoms, hypoventilation, and weight loss. The mean age of onset in those with Perry syndrome is 49 years (range: 35-70 years), and the mean disease duration is five years (range: 2-14 years). In most affected persons, the reported cause/circumstance of death relates to sudden death/hypoventilation or suicide. [from GeneReviews]

The spectrum of DCTN1-related neurodegeneration includes Perry syndrome, distal hereditary motor neuronopathy type 7B (dHMN7B), frontotemporal dementia (FTD), motor neuron disease / amyotrophic lateral sclerosis (ALS), and progressive supranuclear palsy. Some individuals present with overlapping phenotypes (e.g., FTD-ALS, Perry syndrome-dHMN7B). Perry syndrome (the most common of the phenotypes associated with DCTN1) is characterized by parkinsonism, neuropsychiatric symptoms, hypoventilation, and weight loss. The mean age of onset in those with Perry syndrome is 49 years (range: 35-70 years), and the mean disease duration is five years (range: 2-14 years). In most affected persons, the reported cause/circumstance of death relates to sudden death/hypoventilation or suicide. [from GeneReviews]

A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by intellectual disability, obesity, macrocephaly, behavioral abnormalities (such as aggressive tantrums and autistic-like behavior), and delayed speech development. Dysmorphic facial features include large, square forehead, prominent supraorbital ridges, broad nasal tip, large ears, prominent lower lip, and minor dental anomalies such as small upper lateral incisors and central incisor gap. [from ORPHANET]

Developmental and epileptic encephalopathy-49 (DEE49) is a severe autosomal recessive neurologic disorder characterized by onset of seizures in the neonatal period, global developmental delay with intellectual disability and lack of speech, hypotonia, spasticity, and coarse facial features. Some patients may have brain calcifications on imaging (summary by Han et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350. [from OMIM]

Any primary immunodeficiency disease in which the cause of the disease is a mutation in the BCL11B gene. [from MONDO]

An autosomal dominant nonsyndromic deafness that is characterized by moderate loss for low and mid frequencies and mild loss for high frequencies and has material basis in variation in the chromosome region 1q21-q23. [from MONDO]

Spinocerebellar ataxia-49 (SCA49) is an autosomal dominant neurologic disorder characterized initially by gait abnormalities, gaze-evoked nystagmus, and hyperreflexia. The age at onset is highly variable, ranging from the second to seventh decades, even within the same family. The disorder is slowly progressive, and later features may include dysarthria, dysmetria, diplopia, pyramidal signs, and axonal peripheral neuropathy. Brain imaging shows cerebellar atrophy and myelination defects (Corral-Juan et al., 2022). [from OMIM]

Spermatogenic failure-49 (SPGF49) is characterized by male infertility due to multiple morphologic abnormalities of the sperm flagella (MMAF), primarily coiled and short flagella, with markedly reduced or no progressive motility (He et al., 2020). For a discussion of genetic heterogeneity of spermatogenic failure, see 258150. [from OMIM]

Cataract-49 (CTRCT49) is characterized by congenital cataract located in the posterior region of the lens. Visual impairment has onset in early childhood (Sun et al., 2019). [from OMIM]

Primary ciliary dyskinesia-49 (CILD49) without situs inversus is an autosomal recessive disorder characterized by the onset of recurrent respiratory infections, chronic cough, and bronchiectasis in early childhood due to defective ciliary clearance. Affected males also show infertility due to defective flagellar morphology and function. Nasal nitric oxide (NO) levels are normal and situs abnormalities are not observed (Sha et al., 2020; Biebach et al., 2022). For a discussion of genetic heterogeneity of primary ciliary dyskinesia, see CILD1 (244400). [from OMIM]

Autosomal dominant spastic paraplegia-79A with ataxia (SPG79A) is a slowly progressive neurodegenerative disorder characterized predominantly by cerebellar and/or sensory ataxia and spasticity of the lower limbs leading to gait difficulties. The onset is usually in adulthood (median age of 49 years), but can range from childhood to age 70. Additional common features include sensorimotor neuropathy and visual impairment with optic atrophy. The disorder is slowly progressive (Park et al., 2022). [from OMIM]

A well-defined entity within the group of auto inflammatory disorders, it is a rare disease with 49 cases documented so far. It affects mainly young adults and is characterised by recurrent attacks of fever and deep abscess-like collections, most frequently localised in the abdomen. Aseptic abscesses may be either isolated or associated with an underlying condition such as relapsing polychondritis or inflammatory bowel disease. Antibiotics fail to cure the patients but dramatic improvements are seen with corticosteroids and immunosuppressive drugs. [from SNOMEDCT_US]

Moderate mental retardation is defined as an intelligence quotient (IQ) in the range of 35-49. [from HPO]

Neurodevelopmental disorder with spastic paraplegia and microcephaly (NEDSPM) is an autosomal recessive neurologic syndrome characterized by delayed psychomotor development with delayed walking, moderately to severely impaired intellectual development, and poor or absent speech. More severely affected individuals show poor overall growth with progressive microcephaly, axial hypotonia, oromotor dysfunction with drooling, joint contractures, and spastic paraplegia resulting in walking difficulties. Some patients may develop seizures; nonspecific dysmorphic features have also been reported (summary by Hengel et al., 2018 and Ouyang et al., 2019). [from OMIM]

A rare gonosome anomaly syndrome characterised by a eunuchoid habitus with gynaecoid fat distribution and shape, normal to tall stature, moderate to severe intellectual disability, distinctive facial features (prominent forehead, epicanthic folds, broad nasal bridge, prognathism), gynaecomastia, hypogonadism, cryptorchidism, small penis and behavioural abnormalities (including solitary, passive disposition but prone to aggressive outbursts, autistic). Skeletal malformations, such as delayed bone age, fifth finger clinodactyly, elbow malformations and slow molar development may also be associated. [from SNOMEDCT_US]