Muscular hypotonia, and Clinodactyly of the 5th finger

Glycosylphosphatidylinositol biosynthesis defect-17 is an autosomal recessive disorder characterized by variable neurologic deficits that become apparent in infancy or early childhood. Patients may present with early-onset febrile or afebrile seizures that tend to be mild or controllable. Other features may include learning disabilities, autism, behavioral abnormalities, hypotonia, and motor deficits. The phenotype is relatively mild compared to that of other GPIBDs (summary by Nguyen et al., 2018).For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (OMIM ).

• Seizures
• Global developmental delay
• Generalized hypotonia
• Microcephaly
• Growth delay

SOURCES: OMIM MENDELIAN

Cerebellar ataxia-hypogonadism syndrome is a very rare autosomal recessive neurodegenerative disorder characterized by the combination of progressive cerebellar ataxia with onset from early childhood to the fourth decade, and hypogonadotropic hypogonadism (delayed puberty and lack of secondary sex characteristics). Cerebellar ataxia-hypogonadism syndrome belongs to a clinical continuum of neurodegenerative disorders along with clinically overlapping disorders such as ataxia-hypogonadism-choroidal dystrophy syndrome (see this term).

CEREBELLAR ATAXIA-HYPOGONADISM SYNDROME Is also known as luteinizing hormone-releasing hormone deficiency with ataxia|gordon-holmes syndrome

• Short stature
• Ataxia
• Nystagmus
• Muscular hypotonia
• Optic atrophy

SOURCES: ORPHANET MENDELIAN

16P13.2 MICRODELETION SYNDROME Is also known as del(16)(p13.2)|monosomy 16p13.2

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

SOURCES: ORPHANET OMIM MENDELIAN

Macrocephaly-developmental delay syndrome is a rare, intellectual disability syndrome characterized by macrocephaly, mild dysmorphic features (frontal bossing, long face, hooded eye lids with small, downslanting palpebral fissures, broad nasal bridge, and prominent chin), global neurodevelopmental delay, behavioral abnormalities (e.g. anxiety, stereotyped movements) and absence or generalized tonic-clonic seizures. Additional features reported in some patients include craniosynostosis, fifth finger clinodactyly, recurrent pneumonia, and hepatosplenomegaly.

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• High palate

SOURCES: ORPHANET OMIM MENDELIAN

MASA syndrome (Mental retardation, Aphasia, Spastic paraplegia, Adducted thumbs) is a historical term used to describe a phenotype now considered to be part of the X-linked L1 clinical spectrum (L1 syndrome, see this term). MASA is characterized by mild to moderate intellectual deficit, delayed development of speech, hypotonia progressing to spasticity or spastic paraplegia, adducted thumbs, and mild to moderate distension of the cerebral ventricles.

MASA SYNDROME Is also known as spastic paraplegia 1, x-linked|thumb, congenital clasped, with mental retardation|gareis-mason syndrome|intellectual disability-aphasia-shuffling gait-adducted thumbs syndrome|clasped thumb and mental retardation|spg1|mental retardation, aphasia, shufflin

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

SOURCES: OMIM ORPHANET MENDELIAN

Intellectual disability-obesity-brain malformations-facial dysmorphism syndrome is a rare, syndromic intellectual disability primarily characterized by moderate to severe intellectual disability, true-to-relative microcephaly and brain abnormalities including a thin corpus callosum, cerebellar hypoplasia, cerebral white matter hypoplasia and multi-focal hyperintensity of cerebral white matter on MRI. Obesity and distinctive craniofacial dysmorphism (including brachycephaly, round face, straight eyebrows, synophrys, hypertelorism, epicanthus, wide and depressed nasal bridge, protruding ears with uplifted lobe, downslanting corners of the mouth) are additional features.

INTELLECTUAL DISABILITY-OBESITY-BRAIN MALFORMATIONS-FACIAL DYSMORPHISM SYNDROME Is also known as autosomal recessive intellectual disability due to trappc9 deficiency

• Seizures
• Global developmental delay
• Microcephaly
• Hypertelorism
• Abnormal facial shape

SOURCES: ORPHANET MENDELIAN

Multiple epiphyseal dysplasia type 4 is a multiple epiphyseal dysplasia with a late-childhood onset, characterized by joint pain involving hips, knees, wrists, and fingers with occasional limitation of joint movements, deformity of hands, feet, and knees (club foot, clinodactyly, brachydactyly), scoliosis and slightly reduced adult height. Radiographs display flat epiphyses with early arthritis of the hip, and double-layered patella. Multiple epiphyseal dysplasia type 4 follows an autosomal recessive mode of transmission. The disease is allelic to diastrophic dwarfism, atelosteogenesis type 2 and achondrogenesis type 1B with whom it forms a clinical continuum.

MULTIPLE EPIPHYSEAL DYSPLASIA TYPE 4 Is also known as med4|multiple epiphyseal dysplasia, autosomal recessive|rmed|edm4|polyepiphyseal dysplasia type 4|multiple epiphyseal dysplasia with bilayered patellae|autosomal recessive multiple epiphyseal dysplasia|multiple epiphyseal dysplasia with clubfoot

• Short stature
• Generalized hypotonia
• Scoliosis
• Muscular hypotonia
• Cleft palate

SOURCES: MESH OMIM ORPHANET MENDELIAN

Deletion 6q16 syndrome is a Prader-Willi like syndrome characterized by obesity, hyperphagia, hypotonia, small hands and feet, eye/vision anomalies, and global developmental delay.

6Q16 DELETION SYNDROME Is also known as del(6)(q16)|prader-willi-like syndrome due to deletion 6q16|monosomy 6q16

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

SOURCES: ORPHANET MENDELIAN

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

SOURCES: OMIM MENDELIAN

17p13.3 microduplication syndrome is characterized by variable psychomotor delay and dysmorphic features.

17P13.3 MICRODUPLICATION SYNDROME Is also known as 17p13.3 duplication syndrome|dup(17)(p13.3)|trisomy 17p13.3

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

SOURCES: MESH OMIM ORPHANET MENDELIAN