Delayed speech and language development, and Small for gestational age

High match MENTAL RETARDATION, X-LINKED 19; MRX19

X-linked mental retardation-19 (MRX19) is a nonsyndromic form of mild to moderate mental retardation. Carrier females may be mildly affected. Mutation in the RPS6KA3 gene also causes Coffin-Lowry syndrome (CLS ), a mental retardation syndrome with dysmorphic facial features and skeletal anomalies. Some patients with RPS6KA3 mutations have an intermediate phenotype with mental retardation and only mild anomalies reminiscent of CLS. These individuals have mutations resulting in some residual protein function, which likely explains the milder phenotype (summary by Field et al., 2006).

• Intellectual disability
• Short stature
• Generalized hypotonia
• Pica
• Scoliosis

SOURCES: UMLS MONDO MESH OMIM

High match HYPERTHYROIDISM, NONAUTOIMMUNE

Familial non-autoimmune autosomal dominant hyperthyroidism (FNAH) is a rare hyperthyroidism (see this term) characterized by mild to severe hyperthyroidism, presence of goiter, absence of features of autoimmunity, frequent relapses while on treatment and a positive family history.

HYPERTHYROIDISM, NONAUTOIMMUNE Is also known as hyperthyroidism, congenital nonautoimmune, hyperthyroidism, nonautoimmune, autosomal dominant, toxic thyroid hyperplasia, autosomal dominant;familial non-immune hyperthyroidism; resistance to thyroid stimulating hormone

• Autosomal dominant inheritance
• Intellectual disability
• Global developmental delay
• Motor delay
• Ptosis

SOURCES: UMLS MESH MONDO ORPHANET OMIM GARD

High match DYSTONIA, DOPA-RESPONSIVE, DUE TO SEPIAPTERIN REDUCTASE DEFICIENCY

SPR deficiency results in neurologic deterioration due to severe dopamine and serotonin deficiencies in the central nervous system caused by a defect in BH4 synthesis. Clinically, affected individuals show an L-DOPA-responsive, diurnally fluctuating movement disorder usually associated with cognitive delay and severe neurologic dysfunction. BH4 is a required cofactor for the synthesis of the neurotransmitters dopamine and serotonin. BH4 is also a required cofactor for phenylalanine hydroxylase (PAH ), but patients with SPR deficiency do not exhibit overt hyperphenylalaninemia. The lack of hyperphenylalaninemia distinguishes SPR deficiency from other disorders of BH4 synthesis (see, e.g., HPABH4A, {261640}). However, the neurologic phenotype of SPR deficiency resembles the other BH4-deficient disorders (summary by Bonafe et al., 2001 and Friedman et al., 2012).Another form of dopa-responsive dystonia (DTY5 ) is caused by mutation in the gene encoding GTP cyclohydrolase I (GCH1 ), which is also a component of the biopterin synthetic pathway.

DYSTONIA, DOPA-RESPONSIVE, DUE TO SEPIAPTERIN REDUCTASE DEFICIENCY Is also known as sepiapterin reductase deficiency;srd, spr deficiency;autosomal recessive sepiapterin reductase-deficient drd; drd due to srd; spr deficiency; sepiapterin reductase deficiency

• Autosomal recessive inheritance
• Autosomal dominant inheritance
• Intellectual disability
• Seizures
• Global developmental delay

SOURCES: UMLS DOID SCTID ORPHANET MONDO MESH OMIM GARD

High match HYPERPHENYLALANINEMIA, BH4-DEFICIENT, A; HPABH4A

Tetrahydrobiopterin (BH4)-deficient hyperphenylalaninemia (HPA) comprises a genetically heterogeneous group of progressive neurologic disorders caused by autosomal recessive mutations in the genes encoding enzymes involved in the synthesis or regeneration of BH4. BH4 is a cofactor for phenylalanine hydroxylase (PAH ), tyrosine hydroxylase (TH ) and tryptophan hydroxylase (TPH1 ), the latter 2 of which are involved in neurotransmitter synthesis. The BH4-deficient HPAs are characterized phenotypically by hyperphenylalaninemia, depletion of the neurotransmitters dopamine and serotonin, and progressive cognitive and motor deficits (Dudesek et al., 2001).HPABH4A, caused by mutations in the PTS gene, represents the most common cause of BH4-deficient hyperphenylalaninemia (Dudesek et al., 2001). Other forms of BH4-deficient HPA include HPABH4B (OMIM ), caused by mutation in the GCH1 gene (OMIM ), HPABH4C (OMIM ), caused by mutation in the QDPR gene (OMIM ), and HPABH4D (OMIM ), caused by mutation in the PCBD1 gene (OMIM ). Niederwieser et al. (1982) noted that about 1 to 3% of patients with hyperphenylalaninemia have one of these BH4-deficient forms. These disorders are clinically and genetically distinct from classic phenylketonuria (PKU ), caused by mutation in the PAH gene.Two additional disorders associated with BH4 deficiency and neurologic symptoms do not have overt hyperphenylalaninemia as a feature: dopa-responsive dystonia (OMIM ), caused by mutation in the SPR gene (OMIM ), and autosomal dominant dopa-responsive dystonia (DYT5 ), caused by mutation in the GCH1 gene. Patients with these disorders may develop hyperphenylalaninemia when stressed.

HYPERPHENYLALANINEMIA, BH4-DEFICIENT, A; HPABH4A Is also known as hyperphenylalaninemia, tetrahydrobiopterin-deficient, due to pts deficiency, 6-pyruvoyl-tetrahydropterin synthase deficiency, pts deficiency;hyperphenylalaninemia due to 6-pyruvoyltetrahydropterin synthase deficiency

• Autosomal recessive inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia

SOURCES: NCIT OMIM ORPHANET MONDO DOID MESH GARD UMLS

High match MENTAL RETARDATION, AUTOSOMAL DOMINANT 7; MRD7

• Autosomal dominant inheritance
• Intellectual disability
• Seizures
• Generalized hypotonia
• Microcephaly

SOURCES: UMLS ORPHANET OMIM

High match LEUKODYSTROPHY, HYPOMYELINATING, 3; HLD3

Autosomal recessive hypomyelinating leukodystrophy-3 (HLD3) is a severe neurologic disorder characterized by early infantile onset of global developmental delay, lack of development, lack of speech acquisition, and peripheral spasticity associated with decreased myelination in the central nervous system (summary by Feinstein et al., 2010).The disorder is phenotypically similar to X-linked Pelizaeus-Merzbacher disease (PMD ), which is caused by mutation in the PLP1 gene (OMIM ). For a general phenotypic description and a discussion of genetic heterogeneity of HLD, see {312080}.

LEUKODYSTROPHY, HYPOMYELINATING, 3; HLD3 Is also known as ;

• Autosomal recessive inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia

SOURCES: GARD DOID ORPHANET MONDO OMIM UMLS MESH

High match MENTAL RETARDATION, AUTOSOMAL RECESSIVE 5; MRT5

• Autosomal recessive inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Short stature

SOURCES: UMLS MONDO OMIM MESH

High match MENTAL RETARDATION, AUTOSOMAL DOMINANT 22; MRD22

Chromosome 1q43-q44 deletion syndrome is characterized by moderate to severe mental retardation, limited or no speech, and variable but characteristic facial features, including round face, prominent forehead, flat nasal bridge, hypertelorism, epicanthal folds, and low-set ears. Other features may include hypotonia, poor growth, microcephaly, agenesis of the corpus callosum, and seizures. The phenotype is variable, and not all features are observed in all patients, which may be explained in some cases by incomplete penetrance or variable expressivity (summary by Ballif et al., 2012).Patients with autosomal dominant mental retardation-22 have a phenotype similar to that in patients with chromosome 1q43-q44 deletion syndrome (de Munnik et al., 2014).

• Autosomal dominant inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Short stature

SOURCES: MESH MONDO OMIM DOID UMLS

High match MENTAL RETARDATION, AUTOSOMAL DOMINANT 26; MRD26

Autism spectrum disorder due to AUTS2 deficiency is a rare genetic syndromic intellectual disability characterized by global developmental delay and borderline to severe intellectual disability, autism spectrum disorder with obsessive behavior, stereotypies, hyperactivity but frequently friendly and affable personality, feeding difficulties, short stature, muscular hypotonia, microcephaly, characteristic dysmorphic features (hypertelorism, high arched eyebrows, ptosis, deep and/or broad nasal bridge, broad/prominent nasal tip, short and/or upturned philtrum, narrow mouth, and micrognathia), and skeletal anomalies (kyphosis and/or scoliosis, arthrogryposis, slender habitus and extremities). Other clinical features may include hernias, congenital heart defects, cryptorchidism and seizures.

MENTAL RETARDATION, AUTOSOMAL DOMINANT 26; MRD26 Is also known as ;asd due to auts2 deficiency; auts2 syndrome

• Autosomal dominant inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Short stature

SOURCES: UMLS OMIM ORPHANET MONDO DOID

Medium match MEIER-GORLIN SYNDROME 6; MGORS6

• Autosomal dominant inheritance
• Global developmental delay
• Hearing impairment
• Micrognathia
• Strabismus

SOURCES: UMLS MONDO OMIM