Microcephaly, and Esotropia

X-linked colobomatous microphthalmia-microcephaly-intellectual disability-short stature syndrome is a rare syndromic microphthalmia disorder characterized by microphthalmia with coloboma (which may involve the iris, cilary body, choroid, retina and/or optic nerve), microcephaly, short stature and intellectual disability. Other eye abnormalities such as pendular nystagmus, esotropia and ptosis may also be present. Additional associated abnormalities include kyphoscoliosis, anteverted pinnae with minimal convolutions, diastema of the incisors and congenital pes varus.

X-LINKED COLOBOMATOUS MICROPHTHALMIA-MICROCEPHALY-INTELLECTUAL DISABILITY-SHORT STATURE SYNDROME Is also known as maine microphthalmos|colobomatous microphthalmia with microcephaly, short stature, and psychomotor retardation|x-linked colobomatous microphthalmia-microcephaly-short stature-psychomotor retardation syndrome

• Intellectual disability
• Global developmental delay
• Short stature
• Microcephaly
• Nystagmus

SOURCES: ORPHANET OMIM MENDELIAN

Bilateral frontoparietal polymicrogyria (BFPP) is a sub-type of polymicrogyria (PMG; see this term), a cerebral cortical malformation characterized by excessive cortical folding and abnormal cortical layering, that involves the frontoparietal region of the brain and that presents with hypotonia, developmental delay, moderate to severe intellectual disability, pyramidal signs, epileptic seizures, non progressive cerebellar ataxia, dysconjugate gaze and/or strabismus.

BILATERAL FRONTOPARIETAL POLYMICROGYRIA Is also known as cerebellar ataxia with neuronal migration defect

• Intellectual disability
• Seizures
• Global developmental delay
• Microcephaly
• Ataxia

SOURCES: OMIM ORPHANET MESH MENDELIAN

Intellectual disability-strabismus syndrome is a rare, genetic, syndromic intellectual disability disorder characterized by moderate to severe intellectual disability and esotropia. Other associated features may include growth failure (underweight, failure to thrive, short stature), microcephaly, tone abnormalities (hypotonia, spasticity), epilepsy, behavioral problems (hyperactivity, aggressiveness), and/or abnormal brain morphology, including arachnoid cyst, cerebral atrophy, mild ventriculomegaly, abnormal CNS myelination or corpus callosum agenesis.

• Intellectual disability
• Generalized hypotonia
• Microcephaly
• Growth delay
• Hypertelorism

SOURCES: ORPHANET OMIM MENDELIAN

• Global developmental delay
• Short stature
• Microcephaly
• Nystagmus
• Motor delay

SOURCES: OMIM MENDELIAN

Autosomal dominant primary microcephaly is a rare, genetic, non-syndromic, developmental defect during embryogenesis malformation syndrome characterized by a congenital, non-progressive, occipitofrontal head circumference that is 2 or more standard deviations below the mean for age, gender and ethnicity which is associated with normal brain architecture and uncomplicated by other abnormalities. Borderline to moderate intellectual disability, as well as early psychomotor delay, may or may not be associated.

• Intellectual disability
• Global developmental delay
• Short stature
• Microcephaly
• Nystagmus

SOURCES: ORPHANET OMIM MESH MENDELIAN

COXPD35 is an autosomal recessive disorder characterized mainly by global developmental delay with intellectual disability, microcephaly, and early-onset myoclonic and other types of seizures. Affected individuals have variable deficiencies of mitochondrial respiratory enzyme complexes resulting from a defect in mitochondrial metabolism (summary by Kernohan et al., 2017).For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (OMIM ).

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

SOURCES: OMIM MENDELIAN

Pontocerebellar hypoplasia type 8 (PCH8) is a novel very rare form of pontocerebellar hypoplasia (see this term) characterized clinically by progressive microencephaly, feeding difficulties, severe developmental delay, although walking may be achieved, hypotonia often associated with increased muscle tone of lower extremities and deep tendon reflexes, joint deformities in the lower extremities, and occasionally complex seizures. PCH8 is caused by a loss-of-function mutation in the CHMP1A gene. MRI demonstrates a pontocerebellar hypoplasia with vermis and hemispheres equally affected and mild to severely reduced cerebral white matter volume with a fully formed very thin corpus callosum.

PONTOCEREBELLAR HYPOPLASIA TYPE 8 Is also known as pontocerebellar hypoplasia due to chmp1a mutation|pch8

• Intellectual disability
• Global developmental delay
• Generalized hypotonia
• Microcephaly
• Nystagmus

SOURCES: OMIM ORPHANET MENDELIAN

Galloway-Mowat syndrome is a renal-neurologic disease characterized by early-onset nephrotic syndrome associated with microcephaly, gyral abnormalities of the brain, and delayed psychomotor development. Most patients have dysmorphic facial features, often including hypertelorism, ear abnormalities, and micrognathia. Other features, such as arachnodactyly and visual impairment, are more variable. Most patients die in the first years of life (summary by Braun et al., 2017).For a general phenotypic description and a discussion of genetic heterogeneity of GAMOS, see GAMOS1 (OMIM ).

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: OMIM MENDELIAN

Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations is a rare cancer-predisposing syndrome, associated with the D1 subgroup of Fanconi anemia (FA), characterized by progressive bone marrow failure, cardiac, brain, intestinal or skeletal abnormalities and predisposition to various malignancies. Bone marrow suppression and the incidence of developmental abnormalities are less frequent than in other FA, but cancer risk is very high with the spectrum of childhood cancers including Wilms tumor, brain tumor (often medulloblastoma) and ALL/AML.

INHERITED CANCER-PREDISPOSING SYNDROME DUE TO BIALLELIC BRCA2 MUTATIONS Is also known as fad1

• Short stature
• Microcephaly
• Growth delay
• Neoplasm
• Failure to thrive

SOURCES: ORPHANET OMIM MESH MENDELIAN

Intellectual disability-feeding difficulties-developmental delay-microcephaly syndrome is a rare, genetic, syndromic intellectual disability disorder characterized by borderline to severe intellectual disability, global development delay, feeding difficulties, microcephaly, short stature and mild facial dysmorphism, including thick eyebrows, long eyelashes, prominent incisors and/or thin upper lip. Other associated features may include hypermetropia with or without esotropia, behavioral anomallies (e.g. autistic behavior, sleeping disturbances), urogenital abnormalities (e.g. crytorchidism, inguinal hernia), single palmar crease, fifth-finger clinodactyly and cardiac defects (e.g. ASD, PDA).

• Intellectual disability
• Global developmental delay
• Short stature
• Generalized hypotonia
• Microcephaly

SOURCES: ORPHANET OMIM MENDELIAN