Global developmental delay, and Lumbar hyperlordosis

Autosomal recessive limb-girdle muscular dystrophy type 2P (LGMD2P) is a form of limb-girdle muscular dystrophy characterized by slowly-progressive, mainly proximal, muscle weakness presenting in early childhood (with difficulties walking and climbing stairs) and mild to severe intellectual disability. Additional manifestations reported include microcephaly, mild increase in thigh or calf muscles, and contractures of the ankles.

AUTOSOMAL RECESSIVE LIMB-GIRDLE MUSCULAR DYSTROPHY TYPE 2P Is also known as muscular dystrophy, limb-girdle, type 2p|muscular dystrophy, limb-girdle, autosomal recessive 16|muscular dystrophy-dystroglycanopathy, limb-girdle, dag1-related|lgmdr16|lgmd2p

• Intellectual disability
• Global developmental delay
• Muscle weakness
• Flexion contracture
• Delayed speech and language development

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

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

Anauxetic dysplasia is a spondyloepimetaphyseal dysplasia characterized by severe short stature of prenatal onset, very short adult height (less than 1 meter), hypodontia, midface hypoplasia, and mild intellectual disability. Vertebrae are ovoid with concave dorsal surfaces in the lumbar region and show delayed bone maturation. Femoral heads and necks are hypoplastic, as are the iliac bodies. Long bones show irregular mineralization of the metaphyses. The first and fifth metacarpals are short and wide with small, late-ossifying epiphyses and bullet-shaped middle phalanges (summary by Barraza-Garcia et al., 2017).For a discussion of genetic heterogeneity of anauxetic dysplasia, see ANXD1 (OMIM ).

ANAUXETIC DYSPLASIA Is also known as spondyloepimetaphyseal dysplasia, menger type|spondyloepimetaphyseal dysplasia, anauxetic type

• Intellectual disability
• Global developmental delay
• Short stature
• Scoliosis
• Growth delay

SOURCES: OMIM ORPHANET MENDELIAN

Macrocephaly, dysmorphic facies, and psychomotor retardation (MDFPMR) is an autosomal recessive neurodevelopmental disorder characterized by large head and somatic overgrowth apparent at birth followed by global developmental delay. Affected individuals have characteristic dysmorphic facial features and persistently large head, but increased birth weight normalizes with age. Additional neurologic features, including seizures, hypotonia, and gait ataxia, may also occur. Patients show severe intellectual impairment (summary by Ortega-Recalde et al., 2015).

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

SOURCES: OMIM MENDELIAN

Spastic paraplegia-severe developmental delay-epilepsy syndrome is a rare, genetic, complex spastic paraplegia disorder characterized by an infantile-onset of psychomotor developmental delay with severe intellectual disability and poor speech acquisition, associated with seizures (mostly myoclonic), muscular hypotonia which may be noted at birth, and slowly progressive spasticity in the lower limbs leading to severe gait disturbances. Ocular abnormalities and incontinence are commonly associated. Other symptoms may include verbal dyspraxia, hypogenitalism, macrocephaly and sensorineural hearing loss, as well as dystonic movements and ataxia with upper limb involvement.

SPASTIC PARAPLEGIA-SEVERE DEVELOPMENTAL DELAY-EPILEPSY SYNDROME Is also known as spastic paraplegia-psychomotor retardation-seizures syndrome|spprs syndrome

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

SOURCES: OMIM ORPHANET MENDELIAN

Dyggve-Melchior-Clausen disease (DMC) is a rare skeletal disorder belonging to the group of spondyloepimetaphyseal dysplasias (see this term).

• Intellectual disability
• Global developmental delay
• Microcephaly
• Scoliosis
• Short neck

SOURCES: OMIM ORPHANET MENDELIAN

Gordon syndrome, also known as distal arthrogryposis type 3, is an extremely rare multiple congenital malformation syndrome characterized by congenital contractures of hand and feet with variable degrees of severity of camptodactyly, clubfoot and, less frequently, cleft palate. Intelligence is normal but in some cases, additional abnormalities, such as short stature, kyphoscoliosis, ptosis, micrognathia, and cryptorchidism may also be present. Gordon syndrome, Marden-Walker syndrome and arthrogryposis with oculomotor limitation and electroretinal anomalies clinically and genetically overlap, and could represent variable expressions of the same condition.

GORDON SYNDROME Is also known as distal arthrogryposis type iia|arthrogryposis multiplex congenita, distal, type iia|camptodactyly, cleft palate, and clubfoot|gordon syndrome|distal arthrogryposis type 3|camptodactyly-cleft palate-clubfoot syndrome

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

SOURCES: MESH ORPHANET OMIM MENDELIAN

Anauxetic dysplasia is a form of spondylometaepiphyseal dysplasia characterized by the prenatal onset of extreme short stature, an adult height of less than 85 cm, hypodontia, and mild mental retardation. Major radiographic characteristics are late-maturing ovoid vertebral bodies with concave dorsal surfaces in the lumbar region; small capital femoral epiphyses; hypoplastic femoral necks; hypoplastic iliac bodies and shallow acetabulae; irregular metaphyseal mineralization and demarcation of the long tubular bones; short first and fifth metacarpals with widened shafts; very short and broad phalanges with small, late-ossifying epiphyses and bullet-shaped middle phalanges; and midface hypoplasia. The number of chondrocytes is severely reduced in the resting and proliferating cartilage, with diminished columnization of the hypertrophic zone (summary by Thiel et al., 2005).Mutations in RMRP also cause 2 milder types of short stature with susceptibility to cancer, cartilage-hair hypoplasia (CHH ) and metaphyseal dysplasia without hypotrichosis (OMIM ). Genetic Heterogeneity of Anauxetic DysplasiaAnauxetic dysplasia-2 (ANXD2 ) is caused by mutation in the POP1 gene on chromosome 8q22.

ANAUXETIC DYSPLASIA 1; ANXD1 Is also known as spondyloepimetaphyseal dysplasia, anauxetic type|anxd|spondylometaepiphyseal dysplasia, anauxetic type|spondylometaepiphyseal dysplasia, menger type|anauxetic dysplasia

• Intellectual disability
• Global developmental delay
• Short stature
• Hypertelorism
• Neoplasm

SOURCES: OMIM MENDELIAN