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Abnormality of speech or vocalization

MedGen UID:
Concept ID:
Disease or Syndrome
Synonyms: Neurological speech impairment; Speech disorder; Speech impairment
HPO: HP:0002167
Monarch Initiative: MONDO:0004730


Abnormalities in the sound of a person's speech or vocalization are not necessarily associated with a known physical cause or due to stuttering or stammering. [from HPO]

Conditions with this feature

Gaucher disease type III
MedGen UID:
Concept ID:
Disease or Syndrome
Gaucher disease (GD) encompasses a continuum of clinical findings from a perinatal lethal disorder to an asymptomatic type. The identification of three major clinical types (1, 2, and 3) and two other subtypes (perinatal-lethal and cardiovascular) is useful in determining prognosis and management. GD type 1 is characterized by the presence of clinical or radiographic evidence of bone disease (osteopenia, focal lytic or sclerotic lesions, and osteonecrosis), hepatosplenomegaly, anemia and thrombocytopenia, lung disease, and the absence of primary central nervous system disease. GD types 2 and 3 are characterized by the presence of primary neurologic disease; in the past, they were distinguished by age of onset and rate of disease progression, but these distinctions are not absolute. Disease with onset before age two years, limited psychomotor development, and a rapidly progressive course with death by age two to four years is classified as GD type 2. Individuals with GD type 3 may have onset before age two years, but often have a more slowly progressive course, with survival into the third or fourth decade. The perinatal-lethal form is associated with ichthyosiform or collodion skin abnormalities or with nonimmune hydrops fetalis. The cardiovascular form is characterized by calcification of the aortic and mitral valves, mild splenomegaly, corneal opacities, and supranuclear ophthalmoplegia. Cardiopulmonary complications have been described with all the clinical subtypes, although varying in frequency and severity.
Fumarase deficiency
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Concept ID:
Disease or Syndrome
Fumarate hydratase (FH) deficiency results in severe neonatal and early infantile encephalopathy that is characterized by poor feeding, failure to thrive, hypotonia, lethargy, and seizures. Dysmorphic facial features include frontal bossing, depressed nasal bridge, and widely spaced eyes. Many affected individuals are microcephalic. A spectrum of brain abnormalities are seen on magnetic resonance imaging, including cerebral atrophy, enlarged ventricles and generous extra-axial cerebral spinal fluid (CSF) spaces, delayed myelination for age, thinning of the corpus callosum, and an abnormally small brain stem. Brain malformations including bilateral polymicrogyria and absence of the corpus callosum can also be observed. Development is severely affected: most affected individuals are nonverbal and nonambulatory, and many die during early childhood. Less severely affected individuals with moderate cognitive impairment and long-term survival have been reported.
Spondylometaphyseal dysplasia, Golden type
MedGen UID:
Concept ID:
Disease or Syndrome
A rare primary bone dysplasia disorder with characteristics of severe short stature, coarse facies, thoracolumbar kyphoscoliosis and enlarged joints with contractures. Psychomotor delay and intellectual disability may also be associated. Radiographic features include flat vertebral bodies, lacy ossification of the metaphyses of long bones and iliac crests, and marked sclerosis of the skull base.
Deficiency of beta-ureidopropionase
MedGen UID:
Concept ID:
Disease or Syndrome
Beta-ureidopropionase deficiency is a rare autosomal recessive inborn error of metabolism due to a defect in pyrimidine degradation. Less than 10 patients have been reported, and the phenotype can range from severe neurologic involvement with mental retardation and seizures to normal neurologic development (Yaplito-Lee et al., 2008).
Dyslexia, susceptibility to, 1
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Concept ID:
Dyslexia is a disorder manifested by difficulty learning to read despite conventional instruction, adequate intelligence, and sociocultural opportunity. It is among the most common neurodevelopmental disorders, with a prevalence of 5 to 12%. Although there is evidence for familial clustering and heritability, the disorder is considered a complex multifactorial trait (Schumacher et al., 2007). Genetic Heterogeneity of Susceptibility to Dyslexia Additional dyslexia susceptibility loci include DYX2 (600202) on chromosome 6p22, DYX3 (604254) on chromosome 2p16-p15, DYX5 (606896) on chromosome 3p12-q13, DYX6 (606616) on chromosome 18p11.2, DYX8 (608995) on chromosome 1p36-p34, and DYX9 (300509) on chromosome Xq27.3. See MAPPING for other possible dyslexia susceptibility loci, including DYX4 and DYX7.
Huntington disease-like 3
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Concept ID:
Disease or Syndrome
A rare Huntington disease-like syndrome with characteristics of childhood-onset progressive neurologic deterioration with pyramidal and extrapyramidal abnormalities, chorea, dystonia, ataxia, gait instability, spasticity, seizures, mutism, and (on brain MRI) progressive frontal cortical atrophy and bilateral caudate atrophy.
Amyotrophic lateral sclerosis type 2, juvenile
MedGen UID:
Concept ID:
Disease or Syndrome
ALS2-related disorder involves retrograde degeneration of the upper motor neurons of the pyramidal tracts and comprises a clinical continuum of the following three phenotypes: Infantile ascending hereditary spastic paraplegia (IAHSP), characterized by onset of spasticity with increased reflexes and sustained clonus of the lower limbs within the first two years of life, progressive weakness and spasticity of the upper limbs by age seven to eight years, and wheelchair dependence in the second decade with progression toward severe spastic tetraparesis and a pseudobulbar syndrome caused by progressive cranial nerve involvement. Juvenile primary lateral sclerosis (JPLS), characterized by upper motor neuron findings of pseudobulbar palsy and spastic quadriplegia without dementia or cerebellar, extrapyramidal, or sensory signs. Juvenile amyotrophic lateral sclerosis (JALS or ALS2), characterized by onset between ages three and 20 years. All affected individuals show a spastic pseudobulbar syndrome (spasticity of speech and swallowing) together with spastic paraplegia. Some individuals are bedridden by age 12 to 50 years.
Alzheimer disease 10
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Concept ID:
Disease or Syndrome
An Alzheimer's disease that is characterized by an associated with variation in the region 7q36.
Giacheti syndrome
MedGen UID:
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Disease or Syndrome
Bardet-Biedl syndrome 1
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Disease or Syndrome
Bardet-Biedl syndrome is an autosomal recessive and genetically heterogeneous ciliopathy characterized by retinitis pigmentosa, obesity, kidney dysfunction, polydactyly, behavioral dysfunction, and hypogonadism (summary by Beales et al., 1999). Eight proteins implicated in the disorder assemble to form the BBSome, a stable complex involved in signaling receptor trafficking to and from cilia (summary by Scheidecker et al., 2014). Genetic Heterogeneity of Bardet-Biedl Syndrome BBS2 (615981) is caused by mutation in a gene on 16q13 (606151); BBS3 (600151), by mutation in the ARL6 gene on 3q11 (608845); BBS4 (615982), by mutation in a gene on 15q22 (600374); BBS5 (615983), by mutation in a gene on 2q31 (603650); BBS6 (605231), by mutation in the MKKS gene on 20p12 (604896); BBS7 (615984), by mutation in a gene on 4q27 (607590); BBS8 (615985), by mutation in the TTC8 gene on 14q32 (608132); BBS9 (615986), by mutation in a gene on 7p14 (607968); BBS10 (615987), by mutation in a gene on 12q21 (610148); BBS11 (615988), by mutation in the TRIM32 gene on 9q33 (602290); BBS12 (615989), by mutation in a gene on 4q27 (610683); BBS13 (615990), by mutation in the MKS1 gene (609883) on 17q23; BBS14 (615991), by mutation in the CEP290 gene (610142) on 12q21, BBS15 (615992), by mutation in the WDPCP gene (613580) on 2p15; BBS16 (615993), by mutation in the SDCCAG8 gene (613524) on 1q43; BBS17 (615994), by mutation in the LZTFL1 gene (606568) on 3p21; BBS18 (615995), by mutation in the BBIP1 gene (613605) on 10q25; BBS19 (615996), by mutation in the IFT27 gene (615870) on 22q12; BBS20 (619471), by mutation in the IFT172 gene (607386) on 9p21; BBS21 (617406), by mutation in the CFAP418 gene (614477) on 8q22; and BBS22 (617119), by mutation in the IFT74 gene (608040) on 9p21. The CCDC28B gene (610162) modifies the expression of BBS phenotypes in patients who have mutations in other genes. Mutations in MKS1, MKS3 (TMEM67; 609884), and C2ORF86 also modify the expression of BBS phenotypes in patients who have mutations in other genes. Although BBS had originally been thought to be a recessive disorder, Katsanis et al. (2001) demonstrated that clinical manifestation of some forms of Bardet-Biedl syndrome requires recessive mutations in 1 of the 6 loci plus an additional mutation in a second locus. While Katsanis et al. (2001) called this 'triallelic inheritance,' Burghes et al. (2001) suggested the term 'recessive inheritance with a modifier of penetrance.' Mykytyn et al. (2002) found no evidence of involvement of the common BBS1 mutation in triallelic inheritance. However, Fan et al. (2004) found heterozygosity in a mutation of the BBS3 gene (608845.0002) as an apparent modifier of the expression of homozygosity of the met390-to-arg mutation in the BBS1 gene (209901.0001). Allelic disorders include nonsyndromic forms of retinitis pigmentosa: RP51 (613464), caused by TTC8 mutation, and RP55 (613575), caused by ARL6 mutation.
MedGen UID:
Concept ID:
Disease or Syndrome
Beta-mannosidosis is an autosomal recessive lysosomal storage disease of glycoprotein catabolism caused by a deficiency of lysosomal beta-mannosidase activity. The most severely affected patients show developmental delay and mental retardation, but there are differing levels of severity and some patients may have comparatively mild disease (Bedilu et al., 2002) The disorder was first described in goats (Jones and Dawson, 1981), who have a more severe neurodegenerative disorder than that seen in humans.
Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures
MedGen UID:
Concept ID:
Disease or Syndrome
NEMMLAS is an autosomal recessive multisystemic disorder characterized by delayed psychomotor development, intellectual disability, and abnormal motor function, including hypotonia, dystonia, ataxia, and spasticity. Patient tissues may show deficiencies in one or more of the mitochondrial oxidative phosphorylation (OXPHOS) enzymes, but this is not a constant finding (summary by Wortmann et al., 2017).
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1
MedGen UID:
Concept ID:
Disease or Syndrome
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) is characterized by fractures (resulting from radiologically demonstrable polycystic osseous lesions), frontal lobe syndrome, and progressive presenile dementia beginning in the fourth decade. The clinical course of PLOSL can be divided into four stages: 1. The latent stage is characterized by normal early development. 2. The osseous stage (3rd decade of life) is characterized by pain and tenderness, mostly in ankles and feet, usually following strain or injury. Fractures are typically diagnosed several years later, most commonly in the bones of the extremities. 3. In the early neurologic stage (4th decade of life), a change of personality begins to develop insidiously. Affected individuals show a frontal lobe syndrome (loss of judgment, euphoria, loss of social inhibitions, disturbance of concentration, and lack of insight, libido, and motor persistence) leading to serious social problems. 4. The late neurologic stage is characterized by progressive dementia and loss of mobility. Death usually occurs before age 50 years.
CEBALID syndrome
MedGen UID:
Concept ID:
Disease or Syndrome
Individuals with MN1 C-terminal truncation (MCTT) syndrome have mild-to-moderate intellectual disability, severe expressive language delay, dysmorphic facial features (midface hypoplasia, downslanting palpebral fissures, hypertelorism, exophthalmia, short upturned nose, and small low-set ears), and distinctive findings on brain imaging (including perisylvian polymicrogyria and atypical rhombencephalosynapsis). Mild-to-moderate prelingual hearing loss (usually bilateral, conductive, and/or sensorineural) is common. Generalized seizures (observed in the minority of individuals) are responsive to anti-seizure medication. There is an increased risk for craniosynostosis and, thus, increased intracranial pressure. To date, 25 individuals with MCTT syndrome have been identified.
Developmental delay, impaired speech, and behavioral abnormalities
MedGen UID:
Concept ID:
Disease or Syndrome
Developmental delay, impaired speech, and behavioral abnormalities (DDISBA) is characterized by global developmental delay apparent from early childhood. Intellectual disability can range from mild to severe. Additional variable features may include dysmorphic facial features, seizures, hypotonia, motor abnormalities such as Tourette syndrome or dystonia, and hearing loss (summary by Cousin et al., 2021).

Professional guidelines


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Recent clinical studies


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Clin Linguist Phon 2022 Jan 2;36(1):34-53. Epub 2021 Apr 26 doi: 10.1080/02699206.2021.1912187. PMID: 33899624Free PMC Article
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Mov Disord 2021 Apr;36(4):803-814. Epub 2020 Dec 29 doi: 10.1002/mds.28465. PMID: 33373483


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Curr Opin Otolaryngol Head Neck Surg 2021 Aug 1;29(4):283-288. doi: 10.1097/MOO.0000000000000735. PMID: 34183557
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Clinical prediction guides

Alzhrani F, Alhabib SF, Yousef M
Acta Otorhinolaryngol Ital 2022 Apr;42(2):182-188. doi: 10.14639/0392-100X-N1668. PMID: 35612511Free PMC Article
Tandon D, Skolnick GB, Naidoo SD, Grames LM, Cradock MM, Smyth MD, Patel KB
Cleft Palate Craniofac J 2021 Nov;58(11):1361-1369. Epub 2021 Jan 20 doi: 10.1177/1055665620984643. PMID: 33467909
Silveri MC
Cerebellum 2021 Apr;20(2):282-294. Epub 2020 Oct 29 doi: 10.1007/s12311-020-01207-6. PMID: 33120434Free PMC Article
de Stadler M, Hersh C
Adv Otorhinolaryngol 2015;76:7-17. Epub 2015 Feb 12 doi: 10.1159/000368004. PMID: 25733227
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Recent systematic reviews

Miller S, Peters K, Ptok M
Ger Med Sci 2022;20:Doc08. Epub 2022 Jun 14 doi: 10.3205/000310. PMID: 35875244Free PMC Article
Rajati F, Ahmadi N, Naghibzadeh ZA, Kazeminia M
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Salari N, Darvishi N, Heydari M, Bokaee S, Darvishi F, Mohammadi M
J Stomatol Oral Maxillofac Surg 2022 Apr;123(2):110-120. Epub 2021 May 24 doi: 10.1016/j.jormas.2021.05.008. PMID: 34033944
Monahan K, Cuzens-Sutton J, Siskind D, Kisely S
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Barbosa RTA, de Oliveira ASB, de Lima Antão JYF, Crocetta TB, Guarnieri R, Antunes TPC, Arab C, Massetti T, Bezerra IMP, de Mello Monteiro CB, de Abreu LC
BMC Pediatr 2018 May 11;18(1):160. doi: 10.1186/s12887-018-1144-5. PMID: 29751828Free PMC Article

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