Failure to thrive, and Hyporeflexia

Bartter syndrome refers to a group of disorders that are unified by autosomal recessive transmission of impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and hypercalciuria. Clinical disease results from defective renal reabsorption of sodium chloride in the thick ascending limb (TAL) of the Henle loop, where 30% of filtered salt is normally reabsorbed (Simon et al., 1997).Patients with antenatal (or neonatal) forms of Bartter syndrome (e.g., BARTS1, {601678}) typically present with premature birth associated with polyhydramnios and low birth weight and may develop life-threatening dehydration in the neonatal period. Patients with classic Bartter syndrome present later in life and may be sporadically asymptomatic or mildly symptomatic (summary by Simon et al., 1996 and Fremont and Chan, 2012).For a discussion of genetic heterogeneity of Bartter syndrome, see {607364}.

• Intellectual disability
• Short stature
• Generalized hypotonia
• Failure to thrive
• Sensorineural hearing impairment

SOURCES: ORPHANET OMIM MENDELIAN

Bartter syndrome refers to a group of disorders that are unified by autosomal recessive transmission of impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and hypercalciuria. Clinical disease results from defective renal reabsorption of sodium chloride in the thick ascending limb (TAL) of the Henle loop, where 30% of filtered salt is normally reabsorbed (Simon et al., 1997).Patients with antenatal (or neonatal) forms of Bartter syndrome typically present with premature birth associated with polyhydramnios and low birth weight and may develop life-threatening dehydration in the neonatal period. Patients with classic Bartter syndrome (see BARTS3, {607364}) present later in life and may be sporadically asymptomatic or mildly symptomatic (summary by Simon et al., 1996 and Fremont and Chan, 2012).For a discussion of genetic heterogeneity of Bartter syndrome, see {607364}.

BARTTER SYNDROME, TYPE 4A, NEONATAL, WITH SENSORINEURAL DEAFNESS; BARTS4A Is also known as bartter syndrome, neonatal, with sensorineural deafness|bsnd

• Intellectual disability
• Generalized hypotonia
• Hearing impairment
• Failure to thrive
• Sensorineural hearing impairment

SOURCES: OMIM MENDELIAN

Autosomal recessive axonal CMT2A2B is a neurologic disorder characterized by onset of peripheral neuropathy in the first years of life. Patients have difficulty walking due to distal muscle weakness; upper limbs may also be affected. Sensory impairment is more variable. Patients often have optic atrophy (summary by Polke et al., 2011).

• Generalized hypotonia
• Hearing impairment
• Scoliosis
• Failure to thrive
• Muscle weakness

SOURCES: OMIM MENDELIAN

Early infantile epileptic encephalopathy-51 is an autosomal recessive severe neurodevelopmental disorder characterized by onset of intractable seizures and hypotonia in the first days or weeks of life. Affected individuals have severely delayed psychomotor development and may show abnormal movements. Brain imaging shows nonspecific abnormalities, such as cerebral atrophy, cerebellar atrophy, and delayed myelination. Laboratory studies showed increased lactate, suggesting mitochondrial dysfunction (summary by Ait-El-Mkadem et al., 2017).For a discussion of genetic heterogeneity of EIEE, see {308350}.

• Seizures
• Global developmental delay
• Generalized hypotonia
• Failure to thrive
• Strabismus

SOURCES: OMIM MENDELIAN

COMBINED OXIDATIVE PHOSPHORYLATION DEFECT TYPE 26 Is also known as coxpd26

• Global developmental delay
• Generalized hypotonia
• Growth delay
• Failure to thrive
• Muscle weakness

SOURCES: OMIM ORPHANET MENDELIAN

Spinal muscular atrophy with respiratory distress type 1 is a rare genetic motor neuron disease characterized by severe respiratory distress/respiratory failure in association with diaphragmatic eventration and palsy, as well as progressive, symmetrical, distal-to-proximal muscle weakness and atrophy (in lower limbs especially). Patients typically have a history of intrauterine growth retardation, low birth weight, feeble cry, weak suck and failure to thrive and present with inspiratory stridor, recurrent episodes of dyspnea or apnea, cyanosis and absent deep tendon reflexes. Kyphosis/scoliosis, foot deformities and joint contractures are frequently associated features.

SPINAL MUSCULAR ATROPHY WITH RESPIRATORY DISTRESS TYPE 1 Is also known as dhmn6|hmn6|neuronopathy, distal hereditary motor, type vi|spinal muscular atrophy, diaphragmatic|autosomal recessive distal spinal muscular atrophy type 1|autosomal recessive spinal muscular atrophy with respiratory distress|dsma1|distal-hmn type 6|diaphr

• Generalized hypotonia
• Growth delay
• Failure to thrive
• Muscle weakness
• Muscular hypotonia

SOURCES: ORPHANET OMIM MENDELIAN

Niemann-Pick disease type A is a very severe subtype of Niemann-Pick disease, an autosomal recessive lysosomal disease, and is characterized clinically by onset in infancy or early childhood with failure to thrive, hepatosplenomegaly, and rapidly progressive neurodegenerative disorders.

NIEMANN-PICK DISEASE TYPE A Is also known as sphingomyelinase deficiency|sphingomyelin lipidosis

• Intellectual disability
• Global developmental delay
• Short stature
• Generalized hypotonia
• Failure to thrive

SOURCES: ORPHANET OMIM MESH MENDELIAN

GLYCOGEN STORAGE DISEASE IV; GSD4 Is also known as andersen disease|brancher deficiency|gbe1 deficiency|amylopectinosis|gsd iv|glycogen branching enzyme deficiency|cirrhosis, familial, with deposition of abnormal glycogen|glycogenosis iv

• Generalized hypotonia
• Failure to thrive
• Muscle weakness
• Muscular hypotonia
• Flexion contracture

SOURCES: OMIM MENDELIAN

NEDMAGA is a neurodevelopmental disorder characterized by infantile-onset global developmental delay with severe to profound intellectual disability, mildly delayed walking with broad-based and unsteady gait, and absence of meaningful language. Patients have features of autism, with repetitive behaviors and poor communication, but usually are socially reactive and have a happy demeanor. More variable neurologic features include mild seizures, spasticity, and peripheral neuropathy (summary by Palmer et al., 2017).

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

SOURCES: OMIM MENDELIAN

EMARDD is a congenital myopathy characterized by proximal and generalized muscle weakness, respiratory difficulties, joint contractures, and scoliosis. More variable features include cleft palate and feeding difficulties. There is variable severity: some patients become ventilator-dependent, never achieve walking, and die in childhood, whereas others have a longer and more favorable course (summary by Logan et al., 2011 and Boyden et al., 2012).

EARLY-ONSET MYOPATHY-AREFLEXIA-RESPIRATORY DISTRESS-DYSPHAGIA SYNDROME Is also known as emardd

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

SOURCES: ORPHANET OMIM MENDELIAN