Generalized hypotonia, and Retinopathy

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

SOURCES: OMIM MENDELIAN

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

SOURCES: OMIM MENDELIAN

Spinocerebellar ataxia-7 (SCA7) is an autosomal dominant neurodegenerative disorder characterized by adult onset of progressive cerebellar ataxia associated with pigmental macular dystrophy. In her classification of ataxia, Harding (1982) referred to progressive cerebellar ataxia with pigmentary macular degeneration as type II ADCA (autosomal dominant cerebellar ataxia). The age at onset, degree of severity, and rate of progression vary among and within families. Associated neurologic signs, such as ophthalmoplegia, pyramidal or extrapyramidal signs, deep sensory loss, or dementia, are also variable. Genetic anticipation is observed and is greater in paternal than in maternal transmissions (Benomar et al., 1994; summary by David et al., 1996).For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (OMIM ).

SPINOCEREBELLAR ATAXIA 7; SCA7 Is also known as opca iii|opca with macular degeneration and external ophthalmoplegia|adca, type ii|olivopontocerebellar atrophy iii|opca3|opca with retinal degeneration|autosomal dominant cerebellar ataxia, type ii

• Global developmental delay
• Generalized hypotonia
• Ataxia
• Nystagmus
• Failure to thrive

SOURCES: OMIM MENDELIAN

Griscelli syndrome type 1 (GS1) represents hypomelanosis with a primary neurologic deficit and without immunologic impairment or manifestations of hemophagocytic syndrome (Menasche et al., 2002). Griscelli syndrome with immune impairment, or Griscelli syndrome type 2 (OMIM ), is caused by mutation in the RAB27A gene (OMIM ). Griscelli syndrome type 3 (OMIM ), characterized by hypomelanosis with no immunologic or neurologic manifestations, can be caused by mutation in the melanophilin (MLPH ) or MYO5A genes.Griscelli syndrome is a rare autosomal recessive disorder that results in pigmentary dilution of the skin and hair, the presence of large clumps of pigment in hair shafts, and an accumulation of melanosomes in melanocytes. While most patients also develop hemophagocytic syndrome, leading to death in the absence of bone marrow transplantation (Menasche et al., 2000), some show severe neurologic impairment early in life without apparent immune abnormalities. Bahadoran et al. (2003) characterized GS1 as comprising hypomelanosis and severe central nervous system dysfunction, corresponding to the 'dilute' phenotype in the mouse, and GS2 as comprising hypomelanosis and lymphohistiocytotic hemophagocytosis, corresponding to the 'ashen' phenotype in mouse.Anikster et al. (2002), Menasche et al. (2002), Huizing et al. (2002), and {3,2:Bahadoran et al. (2003, 2003)} suggested that Elejalde syndrome (OMIM ) in some patients and GS1 represent the same entity.

GRISCELLI SYNDROME TYPE 1 Is also known as partial albinism and primary neurologic disease without hemophagocytic syndrome|griscelli syndrome, cutaneous and neurologic type|griscelli-pruniÉras syndrome type 1|hypopigmentation-neurologic impairment syndrome|griscelli syndrome with neurologic impair

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

SOURCES: MESH OMIM ORPHANET MENDELIAN

Acrocallosal syndrome (ACS) is a polymalformative syndrome characterized by agenesis of corpus callosum (CC), distal anomalies of limbs, minor craniofacial anomalies and intellectual deficit.

ACROCALLOSAL SYNDROME Is also known as acs

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

SOURCES: ORPHANET OMIM MENDELIAN

Autosomal recessive chorioretinopathy-microcephaly syndrome is a rare neuro-opthalmological disease characterized by severe microcephaly of prenatal onset (with diminutive anterior fontanelle and sutural ridging), growth retardation, global developmental delay and intellectual disability (ranging from mild to profound), dysmorphic features (sloping forehead, micro/retrognathia, prominent ears) and visual impairments (including microphthalmia to anophtalmia, generalized retinopathy or multiple punched-out retinal lesions, retinal folds with retinal detachment, optic nerve hypoplasia, strabismus, nystagmus). Brain MRI may show reduced cortical size, cerebral hemispheres, corpus callosum, pachygyria, symplified gyral folding or normal pattern. Other associated features include epilepsy and neurological deficits.

AUTOSOMAL RECESSIVE CHORIORETINOPATHY-MICROCEPHALY SYNDROME Is also known as autosomal recessive chorioretinopathy-microcephaly-intellectual disability syndrome

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

SOURCES: ORPHANET OMIM MENDELIAN

OROFACIODIGITAL SYNDROME XVI; OFD16 Is also known as oral-facial-digital syndrome, type xvi|ofds xvi

• Global developmental delay
• Generalized hypotonia
• Ataxia
• Muscular hypotonia
• Ptosis

SOURCES: OMIM MENDELIAN

Joubert syndrome is an autosomal recessive congenital condition characterized by a unique brainstem and cerebellar malformation comprising cerebellar vermis hypoplasia and/or dysplasia, elongated superior cerebellar peduncles, and deepened interpeduncular fossa, which together are recognized as the 'molar tooth sign' on brain MRI. The most common clinical features include delayed psychomotor development, hypotonia, abnormal respiratory patterns in the neonatal period, oculomotor apraxia, and cerebellar ataxia. Additional features may include retinal degeneration, cystic kidney, liver fibrosis, and polydactyly. It is caused by ciliary defects and is part of a spectrum of disorders known as 'ciliopathies' (summary by Akizu et al., 2014).For a phenotypic description and a discussion of genetic heterogeneity of Joubert syndrome, see {213300}.

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

SOURCES: OMIM MENDELIAN

Autosomal dominant cerebellar ataxias (ADCAs) are a heterogeneous group of disorders that were classified clinically by Harding (1983). Progressive cerebellar ataxia is the primary feature. In ADCA I, cerebellar ataxia of gait and limbs is invariably associated with supranuclear ophthalmoplegia, pyramidal or extrapyramidal signs, mild dementia, and peripheral neuropathy. In ADCA II, macular and retinal degeneration are added to the features. ADCA III is a pure form of late-onset cerebellar ataxia. ADCA I includes SCA1 (OMIM ), SCA2, and SCA3, or Machado-Joseph disease (OMIM ). These 3 are characterized at the molecular level by CAG repeat expansions on 6p24-p23, 12q24.1, and 14q32.1, respectively.For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (OMIM ).

SPINOCEREBELLAR ATAXIA 2; SCA2 Is also known as wadia-swami syndrome|spinocerebellar ataxia, cuban type|olivopontocerebellar atrophy, holguin type|spinocerebellar degeneration with slow eye movements|olivopontocerebellar atrophy ii|spinocerebellar atrophy ii|cerebellar degeneration with slow eye moveme

• Global developmental delay
• Generalized hypotonia
• Ataxia
• Nystagmus
• Muscular hypotonia

SOURCES: OMIM MENDELIAN

NPHS14 is an autosomal recessive syndromic form of steroid-resistant nephrotic syndrome with multisystemic manifestations. Most affected individuals present in infancy or early childhood with progressive renal dysfunction associated with focal segmental glomerulosclerosis (FSGS) and resulting in end-stage renal disease within a few years. Other infants present with primary adrenal insufficiency. Some patients present in utero with fetal hydrops and fetal demise. Additional features of the disorder can include ichthyosis, acanthosis, adrenal insufficiency, immunodeficiency, and neurologic defects (summary by Prasad et al., 2017 and Lovric et al., 2017).For a discussion of genetic heterogeneity of nephrotic syndrome and FSGS, see NPHS1 (OMIM ).

FAMILIAL STEROID-RESISTANT NEPHROTIC SYNDROME WITH ADRENAL INSUFFICIENCY Is also known as primary adrenal insufficiency-steroid-resistant nephrotic syndrome due to sgpl1 deficiency

• Seizures
• Global developmental delay
• Generalized hypotonia
• Hearing impairment
• Microcephaly

SOURCES: ORPHANET OMIM MENDELIAN