Global developmental delay, and Hip dysplasia

Spastic tetraplegia, thin corpus callosum, and progressive microcephaly is an autosomal recessive neurodevelopmental disorder characterized by onset of those features and severely impaired global development in early infancy. Most patients are unable to achieve independent walking or speech; some patients have seizures (summary by Srour et al., 2015 and Heimer et al., 2015).

SPASTIC TETRAPLEGIA-THIN CORPUS CALLOSUM-PROGRESSIVE POSTNATAL MICROCEPHALY SYNDROME Is also known as spastic quadriplegia-thin corpus callosum-progressive postnatal microcephaly syndrome|asct1 deficiency

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

SOURCES: OMIM ORPHANET MENDELIAN

SLC35A3-CDG is a form of congenital disorders of N-linked glycosylation characterized by distal arthrogryposis (mild flexion contractures of the fingers, deviation of the distal phalanges, swan-neck deformity), retromicrognathia, general muscle hypotonia, delayed psychomotor development, autism spectrum disorder (speech delay, abnormal use of speech, difficulties in initiating, understanding and maintaining social interaction, limited non-verbal communication and repetitive behavior), seizures, microcephaly and mild to moderate intellectual disability that becomes apparent with age. The disease is caused by mutations in the gene SLC35A3 (1p21).

AUTISM SPECTRUM DISORDER-EPILEPSY-ARTHROGRYPOSIS SYNDROME Is also known as slc35a3-cdg

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

SOURCES: OMIM ORPHANET MENDELIAN

Microcephalic primordial dwarfism, Dauber type is a rare, genetic developmental defect during embryogenesis characterized by severe pre- and postnatal growth retardation, severe microcephaly, severe developmental delay and intelletual disability, severe adult short stature and facial dysmorphism (incl. hypotelorism, small ears, prominent nose). Other reported features include skeletal anomalies (Madelung deformity, clinodactyly, mild lumbar scoliosis, bilateral hip dysplasia) and seizures. Absence of thelarche and menarche is also associated.

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

SOURCES: ORPHANET OMIM MENDELIAN

GPIBD15 is an autosomal recessive disorder characterized by delayed psychomotor development, variable intellectual disability, hypotonia, early-onset seizures in most patients, and cerebellar atrophy, resulting in cerebellar signs including gait ataxia and dysarthria. The disorder is caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis (summary by Nguyen et al., 2017).For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (OMIM ).

GLYCOSYLPHOSPHATIDYLINOSITOL BIOSYNTHESIS DEFECT 15; GPIBD15 Is also known as developmental delay, epilepsy, cerebellar atrophy, and osteopenia

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

SOURCES: OMIM MENDELIAN

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

SOURCES: OMIM MENDELIAN

Dihydropyrimidinase (DPD) deficiency is a very rare pyrimidine metabolism disorder with a variable clinical presentation including gastrointestinal manifestations (feeding problems, cyclic vomiting, gastroesophageal reflux, malabsorption with villous atrophy), hypotonia, intellectual deficit, seizures, and less frequently growth retardation, failure to thrive, microcephaly and autism. Asymptomatic cases are also reported. DPD deficiency increases the risk of 5-FU toxicity.

DIHYDROPYRIMIDINURIA Is also known as dihydropyrimidinase deficiency|dph deficiency|dihydropyrimidinuria|dpys deficiency

• Intellectual disability
• Seizures
• Global developmental delay
• Growth delay
• Abnormal facial shape

SOURCES: OMIM ORPHANET MENDELIAN

• Global developmental delay
• Generalized hypotonia
• Microcephaly
• Failure to thrive
• Low-set ears

SOURCES: OMIM MENDELIAN

Steel syndrome is characterized by characteristic facies, dislocated hips and radial heads, carpal coalition (fusion of carpal bones), short stature, scoliosis, and cervical spine anomalies. The dislocated hips are resistant to surgical intervention (summary by Flynn et al., 2010).

STEEL SYNDROME Is also known as bilateral hip and radial head dislocations-short stature-scoliosis-carpal coalitions-pes cavus-facial dysmorphism syndrome|dislocated hips and radial heads, carpal coalition, scoliosis, and short stature

• Global developmental delay
• Short stature
• Hearing impairment
• Scoliosis
• Hypertelorism

SOURCES: OMIM ORPHANET MENDELIAN

Seckel syndrome is a type of microcephalic primordial dwarfism that is characterized by a proportionate dwarfism of prenatal onset, a severe microcephaly, a typical dysmorphic face (bird-like), and mild to severe intellectual disability.

• Intellectual disability
• Short stature
• Microcephaly
• Scoliosis
• Micrognathia

SOURCES: ORPHANET MENDELIAN

NDAGSCW is a neurodevelopmental disorder characterized by severely delayed psychomotor development apparent from infancy. Affected individuals have delayed and difficulty walking, intellectual disability, absent speech, and variable additional features, including hip dysplasia, tapering fingers, and seizures. Brain imaging shows decreased cortical white matter, often with decreased cerebellar white matter, thin corpus callosum, and thin brainstem (summary by Lamers et al., 2017).

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

SOURCES: OMIM MENDELIAN