Hydrocephalus, and Retinopathy

cblC type methylmalonic acidemia with homocystinuria is a form of methylmalonic acidemia with homocystinuria (see this term), an inborn error of vitamin B12 (cobalamin) metabolism characterized by megaloblastic anemia, lethargy, failure to thrive, developmental delay, intellectual deficit and seizures.

METHYLMALONIC ACIDEMIA WITH HOMOCYSTINURIA, TYPE CBLC Is also known as methylmalonic aciduria with homocystinuria, type cblc|combined defect in adenosylcobalamin and methylcobalamin synthesis, type cblc|cobalamin c defect|cblc defect

• Seizures
• Microcephaly
• Failure to thrive
• Fatigue
• Hydrocephalus

SOURCES: ORPHANET MENDELIAN

Xeroderma pigmentosum/Cockayne syndrome complex (XP/CS complex) is characterized by the cutaneous features of xeroderma pigmentosum (XP) (see this term) together with the systemic and neurological features of Cockayne syndrome (CS; see this term).

XERODERMA PIGMENTOSUM-COCKAYNE SYNDROME COMPLEX Is also known as xp/cs complex

• Intellectual disability
• Global developmental delay
• Short stature
• Hearing impairment
• Microcephaly

SOURCES: ORPHANET MENDELIAN

Joubert syndrome is a genetically heterogeneous autosomal recessive disorder characterized by a specific hindbrain malformation, which is referred to as the 'molar tooth sign' (MTS) on brain MRI, hypotonia, developmental delay, oculomotor apraxia, and breathing abnormalities. The complex brainstem malformation consists of cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (Maria et al., 1997). Additional features sometimes associated with Joubert syndrome include retinal anomalies, polydactyly, hepatic fibrosis, and renal disease. These related disorders are often referred to as 'cerebellooculorenal syndromes' (CORSs) (Chance et al., 1999; Satran et al., 1999).

JOUBERT SYNDROME 2; JBTS2 Is also known as cors2|cerebellooculorenal syndrome 2

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

SOURCES: MESH OMIM MENDELIAN

1p31p32 microdeletion syndrome is a rare chromosomal anomaly syndrome, resulting from the partial deletion of the short arm of chromosome 1, characterized by developmental delay, corpus callosum agenesis/hypoplasia and craniofacial dysmorphism, such as macrocephaly (caused by hydrocephalus or ventriculomegaly), low-set ears, anteverted nostrils and micrognathia. Urinary tract defects (e.g. vesicoureteral reflux, urinary incontinence) are also frequently associated. Other reported variable manifestations include hypotonia, tethered spinal cord, Chiari type I malformation and seizures.

1P31P32 MICRODELETION SYNDROME Is also known as monosomy 1p31p32|del(1)(p31p32)

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Failure to thrive

SOURCES: OMIM ORPHANET MENDELIAN

Walker-Warburg Syndrome (WWS) is a rare form of congenital muscular dystrophy associated with brain and eye abnormalities.

WALKER-WARBURG SYNDROME Is also known as hard syndrome|cerebroocular dysplasia-muscular dystrophy syndrome|hydrocephalus, agyria, and retinal dysplasia|walker-warburg syndrome or muscle-eye-brain disease, pomt1-related|wws|hydrocephalus-agyria-retinal dysplasia syndrome|cod-md syndrome

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

SOURCES: ORPHANET OMIM MENDELIAN

Interstitial 9q22.3 microdeletion is associated with a phenotype including macrocephaly, overgrowth and trigonocephaly. Psychomotor delay, hyperactivity and distinctive facial features were also observed. It has been described in two unrelated children.

MONOSOMY 9Q22.3 Is also known as microdeletion 9q22.3

• Intellectual disability
• Seizures
• Global developmental delay
• Strabismus
• Muscular hypotonia

SOURCES: ORPHANET MESH MENDELIAN

Mucopolysaccharidosis II is a rare X-linked recessive disorder caused by deficiency of the lysosomal enzyme iduronate sulfatase, leading to progressive accumulation of glycosaminoglucans in nearly all cell types, tissues, and organs. Patients with MPS II excrete excessive amounts of chondroitin sulfate B (dermatan sulfate) and heparitin sulfate (heparan sulfate) in the urine (McKusick, 1972; Wraith et al., 2008).

MUCOPOLYSACCHARIDOSIS, TYPE II; MPS2 Is also known as hunter syndrome|sulfoiduronate sulfatase deficiency|sids deficiency|mps ii|ids deficiency|iduronate 2-sulfatase deficiency

• Intellectual disability
• Seizures
• Global developmental delay
• Hearing impairment
• Ptosis

SOURCES: OMIM MENDELIAN

Mucopolysaccharidosis type VI is an autosomal recessive lysosomal storage disorder resulting from a deficiency of arylsulfatase B. Clinical features and severity are variable, but usually include short stature, hepatosplenomegaly, dysostosis multiplex, stiff joints, corneal clouding, cardiac abnormalities, and facial dysmorphism. Intelligence is usually normal (Azevedo et al., 2004).

MUCOPOLYSACCHARIDOSIS, TYPE VI; MPS6 Is also known as maroteaux-lamy syndrome|mps vi|n-acetylgalactosamine-4-sulfatase deficiency|arsb deficiency|arylsulfatase b deficiency

• Intellectual disability
• Short stature
• Hearing impairment
• Abnormal facial shape
• Flexion contracture

SOURCES: OMIM MENDELIAN

Encephalocraniocutaneous lipomatosis (ECCL) is a neurocutaneous disorder characterized by ocular anomalies, skin lesions, and central nervous system (CNS) anomalies (Moog et al., 2007).The malformations in ECCL are patchy and asymmetric. The most characteristic skin anomaly is nevus psiloliparus, a well-demarcated, alopecic fatty tissue nevus on the scalp, seen in 80% of affected individuals. Other dermatologic features include frontotemporal or zygomatic subcutaneous fatty lipomas, non-scarring alopecia, focal dermal hypoplasia or aplasia of the scalp, periocular skin tags, and pigmentary abnormalities following the lines of Blaschko. Choristomas of the eye (epibulbar dermoids or lipodermoids) are also present in 80% of patients, and can be unilateral or bilateral. Characteristic CNS features in ECCL include intracranial and intraspinal lipomas, seen in 61% of patients, and less often cerebral asymmetry, arachnoid cysts, enlarged ventricles, and leptomeningeal angiomatosis. A predisposition to low-grade gliomas has also been observed. Seizures and intellectual disability are common, but one-third of affected individuals have normal intellect. Skeletal manifestations include bone cysts and jaw tumors, such as odontomas, osteomas, and ossifying fibromas (summary by Bennett et al., 2016).

ENCEPHALOCRANIOCUTANEOUS LIPOMATOSIS Is also known as haberland syndrome

• Intellectual disability
• Seizures
• Global developmental delay
• Neoplasm
• Failure to thrive

SOURCES: OMIM MESH ORPHANET MENDELIAN

Combined methylmalonic aciduria (MMA) and homocystinuria is a genetically heterogeneous disorder of cobalamin (cbl; vitamin B12) metabolism. The defect causes decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl), which results in decreased activity of the respective enzymes methylmalonyl-CoA mutase (MUT ) and methyltetrahydrofolate:homocysteine methyltransferase, also known as methionine synthase (MTR ). Different forms of the disorder have been classified according to complementation groups of cells in vitro: cblC, cblD (OMIM ), cblF (OMIM ), and cblJ (OMIM ).Isolated methylmalonic acidurias have also been classified by complementation groups: MMA 'mut' (OMIM ) is caused by mutation in the MUT gene on chromosome 6p21; MMA cblA (OMIM ) is caused by mutation in the MMAA gene (OMIM ) on 4q31; and MMA cblB (OMIM ) is caused by mutation in the MMAB gene (OMIM ) on 12q24.Methylmalonic aciduria and homocystinuria, cblC type, is the most common inborn error of vitamin B12 (cobalamin) metabolism, with about 250 known cases (Lerner-Ellis et al., 2006). Affected individuals may have developmental, hematologic, neurologic, metabolic, ophthalmologic, and dermatologic clinical findings. Although considered a disease of infancy or childhood, some individuals develop symptoms in adulthood (Rosenblatt et al., 1997).

METHYLMALONIC ACIDURIA AND HOMOCYSTINURIA, CBLC TYPE; MAHCC Is also known as vitamin b12 metabolic defect with combined deficiency of methylmalonyl-coa mutase and homocysteine:methyltetrahydrofolate methyltransferase|methylmalonic aciduria and homocystinuria, vitamin b12-responsive|methylmalonic acidemia and homocystinuria, cblc t

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Hearing impairment

SOURCES: ORPHANET OMIM MENDELIAN