Delayed speech and language development, and Frontal bossing

High match MENTAL RETARDATION, X-LINKED 93; MRX93

MENTAL RETARDATION, X-LINKED 93; MRX93 Is also known as mental retardation, x-linked, with macrocephaly

• Intellectual disability
• Generalized hypotonia
• Muscular hypotonia
• Cryptorchidism
• Delayed speech and language development

SOURCES: MESH OMIM UMLS MONDO

High match WAISMAN SYNDROME; WSMN

Early-onset parkinsonism with intellectual deficit is a basal ganglia disorder characterised by parkinsonian-type symptoms (postural changes, tremor, rigidity), megalencephaly and variable intellectual deficit. Other signs are frontal bossing, persistent frontal lobe reflexes, strabismus and seizures. It has been described in three generations of one family. Transmission is X-linked, and the gene is located on chromosomal region Xq27.3-qter.

WAISMAN SYNDROME; WSMN Is also known as parkinsonism, early-onset, with mental retardation, basal ganglion disorder with mental retardation;bgmr, wsn;laxova-opitz syndrome; waisman syndrome

• Intellectual disability
• Seizures
• Global developmental delay
• Strabismus
• Cognitive impairment

SOURCES: OMIM MONDO MESH UMLS SCTID GARD ORPHANET

High match FG SYNDROME 2; FGS2

Although the phenotypic spectrum and severity of FG syndrome is wide, the cardinal features include congenital hypotonia, delayed speech development, relative macrocephaly, dysmorphic facies, and anal anomalies or severe constipation (Unger et al., 2007).For a general phenotypic description and a discussion of genetic heterogeneity of FG syndrome, see FGS1 (OMIM ).

• Intellectual disability
• Generalized hypotonia
• Failure to thrive
• Delayed speech and language development
• Macrocephaly

SOURCES: OMIM UMLS GARD MONDO

High match CRANIOSYNOSTOSIS 4; CRS4

Craniosynostosis is a primary abnormality of skull growth involving premature fusion of the cranial sutures such that the growth velocity of the skull often cannot match that of the developing brain. This produces skull deformity and, in some cases, raises intracranial pressure, which must be treated promptly to avoid permanent neurodevelopmental disability (summary by Fitzpatrick, 2013). Craniosynostosis-4 includes lambdoid, sagittal, metopic, coronal, and multisuture forms.For a discussion of genetic heterogeneity of craniosynostosis, see CRS1 (OMIM ).

• Autosomal dominant inheritance
• Hypertelorism
• Ptosis
• Depressed nasal bridge
• Delayed speech and language development

SOURCES: MONDO UMLS OMIM

High match HYPERMETHIONINEMIA DUE TO ADENOSINE KINASE DEFICIENCY

Hypermethioninemia encephalopathy due to adenosine kinase deficiency is a rare inborn error of metabolism disorder characterized by persistent hypermethioninemia with increased levels of S-adenosylmethionine and S-adenosylhomocysteine which manifests with encephalopathy, severe global developmental delay, mild to severe liver dysfunction, hypotonia and facial dysmorphism (most significant is frontal bossing, macrocephaly, hypertelorism and depressed nasal bridge). Epileptic seizures, hypoglycemia and/or cardiac defects (pulmonary stenosis, atrial and/or ventricular septal defect, coarctation of the aorta) may be associated. Clinical picture may range from neurological symptoms only to multi-organ involvement.

HYPERMETHIONINEMIA DUE TO ADENOSINE KINASE DEFICIENCY Is also known as mental retardation, autosomal recessive 8, formerly;mrt8, formerly;adk hypermethioninemia; hypermethioninemia encephalopathy due to adk deficiency

• Autosomal recessive inheritance
• Seizures
• Global developmental delay
• Generalized hypotonia
• Hearing impairment

SOURCES: ORPHANET DOID UMLS OMIM MESH MONDO

High match ECTODERMAL DYSPLASIA, ANHIDROTIC, WITH T-CELL IMMUNODEFICIENCY, AUTOSOMAL DOMINANT

Mutations in the NFKBIA gene result in functional impairment of NFKB1 (OMIM ), a master transcription factor required for normal activation of immune responses. Interruption of NFKB1 signaling results in decreased production of proinflammatory cytokines and certain interferons, rendering patients susceptible to infection (McDonald et al., 2007).

• Autosomal dominant inheritance
• Growth delay
• Failure to thrive
• Delayed speech and language development
• Tics

SOURCES: MESH MONDO OMIM UMLS

High match JOUBERT SYNDROME 10; JBTS10

Joubert syndrome is characterized by a specific hindbrain formation, hypotonia, cerebellar ataxia, dysregulated breathing patterns, and developmental delay. Ciliary dysfunction is a key factor in the pathogenesis (Coene et al., 2009).For a phenotypic description and a discussion of genetic heterogeneity of Joubert syndrome, see {213300}.

• Intellectual disability
• Seizures
• Global developmental delay
• Pica
• Growth delay

SOURCES: UMLS DOID MESH OMIM MONDO

High match DEVELOPMENTAL AND SPEECH DELAY DUE TO SOX5 DEFICIENCY

Developmental and speech delay due to SOX5 deficiency is a rare genetic syndromic intellectual disability characterized by mild to severe global developmental delay, intellectual disability and behavioral abnormalities, hypotonia, strabismus, optic nerve hypoplasia and mild facial dysmorphic features (down slanting palpebral fissures, frontal bossing, crowded teeth, auricular abnormalities and prominent philtral ridges). Other associated clinical features may include seizures and skeletal anomalies (kyphosis/scoliosis, pectus deformities).

• Intellectual disability
• Seizures
• Scoliosis
• Strabismus
• Motor delay

SOURCES: ORPHANET

High match MENTAL RETARDATION, X-LINKED, WITH CEREBELLAR HYPOPLASIA AND DISTINCTIVE FACIAL APPEARANCE

X-linked intellectual deficit-cerebellar hypoplasia, also known as OPHN1 syndrome, is a rare syndromic form of cerebellar dysgenesis characterized by moderate to severe intellectual deficit and cerebellar abnormalities.

MENTAL RETARDATION, X-LINKED, WITH CEREBELLAR HYPOPLASIA AND DISTINCTIVE FACIAL APPEARANCE Is also known as mental retardation, x-linked 60, formerly;mrx60, formerly;ophn1 syndrome; oligophrenin-1 syndrome

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Ataxia

SOURCES: ORPHANET SCTID GARD MESH OMIM UMLS MONDO

High match MACROCEPHALY, DYSMORPHIC FACIES, AND PSYCHOMOTOR RETARDATION; MDFPMR

Macrocephaly, dysmorphic facies, and psychomotor retardation (MDFPMR) is an autosomal recessive neurodevelopmental disorder characterized by large head and somatic overgrowth apparent at birth followed by global developmental delay. Affected individuals have characteristic dysmorphic facial features and persistently large head, but increased birth weight normalizes with age. Additional neurologic features, including seizures, hypotonia, and gait ataxia, may also occur. Patients show severe intellectual impairment (summary by Ortega-Recalde et al., 2015).

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

SOURCES: UMLS OMIM